To see the other types of publications on this topic, follow the link: Autodock vina 1.5.6.
Journal articles on the topic 'Autodock vina 1.5.6'
Create a spot-on reference in APA, MLA, Chicago, Harvard, and other styles
Consult the top 50 journal articles for your research on the topic 'Autodock vina 1.5.6.'
Next to every source in the list of references, there is an 'Add to bibliography' button. Press on it, and we will generate automatically the bibliographic reference to the chosen work in the citation style you need: APA, MLA, Harvard, Chicago, Vancouver, etc.
You can also download the full text of the academic publication as pdf and read online its abstract whenever available in the metadata.
Browse journal articles on a wide variety of disciplines and organise your bibliography correctly.
1
Yanuar, Arry, Rezi Riadhi Syahdi, and Widya Dwi Aryati. "PARAMETER OPTIMIZATION AND VIRTUAL SCREENING INDONESIAN HERBAL DATABASE AS HUMAN IMMUNODEFICIENCY VIRUS -1 INTEGRASE INHIBITOR USING AUTODOCK AND VINA." International Journal of Applied Pharmaceutics 9 (October 30, 2017): 90. http://dx.doi.org/10.22159/ijap.2017.v9s1.51_57.
Full textAbstract:
Objective: Human immunodeficiency virus (HIV-1) is a virus that causes acquired immunodeficiency syndrome, a disease considered to be one of themost dangerous because of its high mortality, morbidity, and infectivity. The emergence of mutant HIV strains has led treatment to target proteaseas reverse transcriptase and integrase enzyme become less effective. This study aims to provide knowledge about the potential of HIV-1 integraseinhibitors for use as guiding compounds in the development of new anti-HIV drugs.Methods: This study used AutoDock and AutoDock Vina for virtual screening of the Indonesian herbal database for inhibitors of HIV-1 integrase andis validated using a database of the directory of useful decoys. Optimization was accomplished by selecting the grid size, the number of calculations,and the addition of two water molecules and a magnesium atom as cofactor.Results: This study determined that the best grid box size is 21.1725×21.1725×21.1725 in unit space size (1 unit space equals to macromolecules 1Ǻ),using AutoDock Vina with EF and AUC values, 3.93 and 0.693, respectively. Three important water molecules have meaning in molecular dockingaround the binding pocket.Conclusions: This study obtained the top ten ranked compounds using AutoDock Vina. The compounds include: Casuarinin; Myricetin-3-O-(2’’,6’’-di-O-α-rhamnosyl)-β-glucoside; 5,7,2’,4’-tetrahydroxy-6,3’-diprenylisoflavone 5-O-(4’’-rhamnosylrhamnoside); myricetin 3-robinobioside; cyanidin3-[6-(6-ferulylglucosyl)-2-xylosylgalactoside]; mesuein, cyanidin 7-(3-glucosyl-6-malonylglucoside)-4’-glucoside; kaempferol 3-[glucosyl-(1→3)-rhamnosyl-(1→6)-galactoside]; 3-O-galloylepicatechin-(4-β→8)-epicatechin-3-O-gallate; and quercetin 4’-glucuronide.
2
Kumar, Kaushal, Mithun Kori, Himanshu Pandey, Satyesh Raj Anand, Neha Mishra, and S. P. Shrivastava. "Study of In Silico on Schiff Base Ligand Against Mycobacterium Tuberculosis." Mediterranean Journal of Chemistry 13, no. 2 (2023): 93. http://dx.doi.org/10.13171/mjc02303211679kumar.
Full textAbstract:
Here, we have synthesized the hetero-atoms containing; 3, 4, 6–Triazabicyclo [6, 3, 1] dodeca–1 (12), 2, 6, 8, 10–pentene–5–thione (TBD) macrocyclic Schiff base ligand for the application in antituberculosis (anti-TB). This TBD ligand moiety has high donor ability due to the presence of three nitrogen donor atoms, which are also the reason for the interaction between the ligand and protein molecule. The TBD Schiff base ligand is characterized by various spectroscopic techniques such as; Fourier-Transform Infrared (FT-IR), Proton Nuclear Magnetic Resonance (1HNMR), and Ultraviolet-Visible (UV-Vis) and Electron Spray Ionization (ESI) Mass spectroscopy, to understand the bond stretching, the electronic environment of protons, electronic transitions (p–p* and <em>n</em>–p*), and M/Z values, respectively. The computational study was carried out to calculate the molecular docking score using AutoDock Vina software against the glutamine protein enzyme (PDB ID-3ZXR). The molecular docking score was –6.3 kcal mol<sup>-1</sup> for the TBD Schiff base ligand, whereas –4.6 kcal mol<sup>-1</sup> is reported for the standard drug (Pyrazinamide). The product formation yield of TBD Schiff base ligand is found to be ~78 % during synthesis.
3
Bekere Belitibo, Dereilo, Asfaw Meressa, Abiy Abebe, et al. "Antibacterial activity of secondary metabolites from the roots of Solanum dasyphyllum: A combined in vitro and in silico study." Bulletin of the Chemical Society of Ethiopia 38, no. 6 (2024): 1843–60. http://dx.doi.org/10.4314/bcse.v38i6.26.
Full textAbstract:
Solanum dasyphyllum is widely utilized for folk medicine in Ethiopia. The chromatographic separation of root extract of S. dasyphyllum led to the isolation of six compounds: tremulacin (1), scopoletin (2), stigmasterol (3), β-sitosterol (4), palmitic acid (5) and 2,3-dihydroxypropyl-9Z,12Z-octadecadienoate (6). The structures of the compounds were determined using NMR (1D and 2D), MS and comparison with literature data. The extract and isolated compounds were in vitro assayed against six bacterial strains and displaying activity against the tested strains. The extract exhibited stronger activity against E. coli, K. pneumoniae, and P. aeruginosa, with MIC values of 0.195±0.0, 0.391±0.0, and 0.195±0.0 mg/mL, respectively. The isolated compounds also showed good antibacterial activity with the highest activity was recorded for compound 2, with MIC values of 0.313±0.0 mg/mL against K. pneumoniae, while for the ciprofloxacin is 0.195±0.0 mg/mL against the same strain. In silico molecular docking analyses were performed for compounds 1, 2 and 3 against E. coli DNA gyrase B, P. aeruginosa LasR protein, and K. pneumoniae using AutoDock Vina and showed better binding activity. The in vitro antibacterial results and in silico analysis of the compounds revealed the potential of these compounds to be lead compound for antibacterial drug discovery. KEY WORDS: Solanum dasyphyllum, Chromatographic separation, Antibacterial activity, Molecular docking Bull. Chem. Soc. Ethiop. 2024, 38(6), 1843-1860. DOI: https://dx.doi.org/10.4314/bcse.v38i6.26
4
B. C., Akhilraj, J. Suresh, K. Rajamani, M. Kumar, R. Gnanam, and S. Raghul. "In Silico Examination of Tinospora cordifolia Phytochemical Constituents towards Sars Cov-2, Dengue and Hepatitis Viruses by Molecular Docking Approach." International Journal of Bio-resource and Stress Management 15, Jun, 6 (2024): 01–09. http://dx.doi.org/10.23910/1.2024.5304.
Full textAbstract:
The experiment was conducted during 2023 at Tamilnadu Agricultural University dept. of medicinal and aromatic crops. Tinospora cordifolia is considered valuable in terms of its immense medicinal properties. Medicinal plants containing phytochemical compounds are considered to be safer and non-toxic than synthetic medicines and in silico analysis of these phytochemical compounds is cost effective, rapid, helps to make decisions and simulate virtually besides useful in optimizing and refining long time experimental trials thereafter. Hence, the present study was mainly focused on in silico research of phytocompounds from T. cordifolia towards dengue, hepatitis A viruses and SARS-CoV-2. The compounds were docked employing AutoDock Vina in PyRx 0.8 a online screening system, onto the crystal patterns of SARS CoV-2 main protease (PDB ID- 2GZ9), dengue virus non-structural protein NS1 (PDB ID- 4OIG) and Hepatitis A virus 3C proteinase (1HAV). The ligands were shortlisted based on their hydrogen bond interactions and binding affinities. The top-ranking molecules showed the range‘s energy state of bonding of covid (-7.6 to -6.7 kcal mol-1), dengue (-7.9 to -7.3 kcal mol-1) and hepatitis (-8.0 to -6.9 kcal mol-1). Based on good binding energy, drug-likeness and efficient pharmacokinetics properties, it was evident that the compounds 3, 3-Dimethyl-1, 5, 13 , 14-tetraoxa-10, 19-diazacyclotricosane-6, 9, 20, 23-tetrone, tdnosporinone, and cordifolioside were conceived as possible deterrents for SARS CoV-2 main protease (Mpro), dengue virus non-structural protein NS1 and hepatitis A virus 3C proteinase respectively.
5
Weni, Mustika, Mega Safithri, and Djarot Sasongko Hami Seno. "Molecular Docking of Active Compounds Piper crocatum on the A-Glucosidase Enzyme as Antidiabetic." Indonesian Journal of Pharmaceutical Science and Technology 7, no. 2 (2020): 64. http://dx.doi.org/10.24198/ijpst.v7i2.21120.
Full textAbstract:
Ethanol extract of Piper crocatum leaves has inhibitory activity of α-glucosidase enzyme. Ethyl acetate fraction from Piper crocatum leaves has the highest antioxidant activity. Previous research has provided information that the ethyl acetate fraction of Piper crocatum leaves has an inhibition of α-glucosidase containing 6XO32ZSP1D, Ethyl L-serinate hydrochloride compound, Schisandrin B compound, Columbin compound, 4- (4-methoxy-phenylamino) -2 compound, 3-dihydro-1H-4a, 9-diazacyclopenta (b) fluorine-10-carbonitrile, compound 6-Amino-4- [3- (benzyloxy) phenyl] -3-tert-butyl-2,4-dihydropyrano [2, 3-c] pyrazole-5-carbonitrile, compound 4 - {{4.6-Bis [(3R, 5S) -3,5-diamino-1-piperydinyl] -1,3,5-triazine-2-yl} amino) benzenesulfonamide and compound 1.1 '- (1,4-butanediyl) bis {2,6-dimethyl-4 - [(3-methyl-1,3-benzothiazol-2 (3H) ylidene) methyl] pyridinium. This study aims to study the interaction between bioactive compounds contained in ethyl acetate fraction of Piper crocatum leaves with α-glucosidase enzyme in In Silico using AutoDock Vina, Columbin shows the lowest binding energy with binding sites with amino acids Ser240, Asp242, His280, Arg315, Glu411, Phe159, Arg442, Tyr158 and Phe303. Columbin has the stability and inhibits the α-glucosidase enzyme from S. cerevisiae better than the seven other compounds, because it has OH and CH3 groups which play a role in the interaction with around the active side of the α-glucosidase enzyme.Keywords: Columbin, In Silico, α-Glucosidase
6
Vlasov, Sergiy V., Oleksandr V. Borysov, Hanna I. Severina, et al. "The synthesis, antimicrobial activity and docking studies of 6-(1H-benzimidazol-2-yl)-5-methylthieno[2,3-d]pyrimidin- 4(3H)-ones with acetamide and 1,2,4-oxadiazol-5-ylmethyl substituents." Journal of Organic and Pharmaceutical Chemistry 19, no. 3(75) (2021): 15–20. http://dx.doi.org/10.24959/ophcj.21.240775.
Full textAbstract:
Aim. To synthesize, study the antimicrobial activity and suggest antimicrobial activity mechanism for the novel derivatives of 6-(1H-benzimidazol-2-yl)-5-methylthieno[2,3-d]pyrimidin-4(3H)-one. Results and discussion. As the result of the targeted modification of 6-(1H-benzimidazol-2-yl)-5-methylthieno[2,3-d]-pyrimidin-4(3H)-one in position 3 with acetamide and 1,2,4-oxadiazol-5-ylmethyl substituents, the compounds, which demonstrated better antimicrobial activity in the agar well diffusion assay than the reference drug Streptomycin, were obtained. To elucidate the mechanism of action of the novel compounds, the docking studies were con-ducted to the active site of the 16S subunit of ribosomal RNA, the proven target for aminoglycoside antibiotics, as well as tRNA (Guanine37-N1)-methyltransferase (TrmD), which inhibitors were considered as a new potential class of antibiotics. Experimental part. By the interaction of 6-(1H-benzimidazol-2-yl)-5-methylthieno[2,3-d]pyrimidin-4(3H)-one with a series of N-arylchloroacetamides and 3-aryl-5-(chloromethyl)-1,2,4-oxadiazoles in DMF in the presence of K2CO3 the target compounds were obtained. The antimicrobial activity was assessed by the agar well diffusion method. The concentration of microbial cells was determined by the McFarland standard; the value was 107 cells in 1 mL of the media. The 18 – 24 hour culture of microorganisms was used for tests. For the bacteria cultivation, Müller-Hinton agar was used, Sabouraud agar was applied for C. albicans cultivation. The compounds were tested as the DMSO solution with the concentration of 100 µg/mL; the volume of the solution was 0.3 mL, the same volume was used for Streptomycin (the concentration 30 µg/mL). The docking studies were performed using Autodock Vina. Crystallographic data for the complexes of Streptomycin with the 16S subunit of ribosomal RNA (1NTB) and its active site, as well as for tRNA (Guanine37-N1)-methyltransferase (EC 2.1.1.228; TrmD) (5ZHN) and its active site were obtained from the Protein Data Bank.Conclusions. It has been determined that 2-[6-(1H-benzimidazol-2-yl)-5-methyl-4-oxothieno[2,3-d]pyrimidin-3(4H)-yl]-N-[4-(ethoxy)phenyl]acetamide, which is the most active as an antimicrobial agent among the compounds tested, also shows the best binding activity towards the active site of tRNA (guanine37-N1)-methyltransferase.
7
Satari, Mieke Hemiawati, Eti Apriyanti, Hendra Dian Adhita Dharsono, Denny Nurdin, Meirina Gartika, and Dikdik Kurnia. "Effectiveness of Bioactive Compound as Antibacterial and Anti-Quorum Sensing Agent from Myrmecodia pendans: An In Silico Study." Molecules 26, no. 9 (2021): 2465. http://dx.doi.org/10.3390/molecules26092465.
Full textAbstract:
Background: antibiotic resistance encourages the development of new therapies, or the discovery of novel antibacterial agents. Previous research revealed that Myrmecodia pendans (Sarang Semut) contain potential antibacterial agents. However, specific proteins inhibited by them have not yet been identified as either proteins targeted by antibiotics or proteins that have a role in the quorum-sensing system. This study aims to investigate and predict the action mode of antibacterial compounds with specific proteins by following the molecular docking approach. Methods: butein (1), biflavonoid (2), 3″-methoxyepicatechin-3-O-epicatechin (3), 2-dodecyl-4-hydroxylbenzaldehyde (4), 2-dodecyl-4-hydroxylbenzaldehyde (5), pomolic acid (6), betulin (7), and sitosterol-(6′-O-tridecanoil)-3-O-β-D-glucopyranoside (8) from M. pendans act as the ligand. Antibiotics or substrates in each protein were used as a positive control. To screen the bioactivity of compounds, ligands were analyzed by Prediction of Activity Spectra for Substances (PASS) program. They were docked with 12 proteins by AutoDock Vina in the PyRx 0.8 software application. Those proteins are penicillin-binding protein (PBP), MurB, Sortase A (SrtA), deoxyribonucleic acid (DNA) gyrase, ribonucleic acid (RNA) polymerase, ribosomal protein, Cytolysin M (ClyM), FsrB, gelatinase binding-activating pheromone (GBAP), and PgrX retrieved from UniProt. The docking results were analyzed by the ProteinsPlus and Discovery Studio software applications. Results: most compounds have Pa value over 0.5 against proteins in the cell wall. In nearly all proteins, biflavonoid (2) has the strongest binding affinity. However, compound 2 binds only three residues, so that 2 is the non-competitive inhibitor. Conclusion: compound 2 can be a lead compound for an antibacterial agent in each pathway.
8
Gebrehiwot, Hadush, Yadessa Melaku, Muhdin Aliye, et al. "Antibacterial and Antioxidant Efficacies of Secondary Metabolites from the Roots of Cyphostemma adenocaule: A Combined In Vitro and In Silico Study." Journal of Tropical Medicine 2024 (March 6, 2024): 1–30. http://dx.doi.org/10.1155/2024/1679695.
Full textAbstract:
Cyphostemma adenocaule is a therapeutic plant traditionally used to treat rabies, snake bite, diarrhea, and wound healing. To address the bioactive compounds exhibiting these activities, we performed a comprehensive study on the roots of the plant. Thus, the present study aims to inspect the in vitro antioxidant and antibacterial efficacies of compounds isolated from the combined dichloromethane : methanol (1 : 1) and methanol extracts of C. adenocaule along with the in silico study of their interaction with selected protein targets. The silica gel column chromatography technique was used for the isolation of compounds, and the antibacterial and antioxidant activities were evaluated using agar disc diffusion and DPPH radical scavenging assays, respectively. Furthermore, in silico molecular docking screening, pharmacokinetics, and toxicity protocols of the compound isolates were performed to offer the potential applications of the compounds in developing novel medications. A BIOVIA Discovery Studio in combination with AutoDock Vina 4.2 software, SwissADME, and ProTox-II prediction web tools were used to generate the molecular docking, pharmacokinetics, and toxicity profiles, respectively. Notably, the chromatographic separation of the combined extracts yielded six known compounds, namely, β-sitosterol (1), 3-hydroxyisoagatholactone (2), ε-viniferin (3), myricetin (4), tricuspidatol A (5), and parthenocissin A (6). The in vitro antibacterial activities revealed the highest inhibition zone by tricuspidatol A (5) (16.67 ± 0.47), showcasing its potent activity against S. aureus at 2 mg/mL, compared to ciprofloxacin (21.50 ± 0.41). ε-Viniferin (3) (IC50: 0.32 μg/mL) exhibited greater antioxidant activity than the others and displayed promising results compared to ascorbic acid (0.075 μg/mL). The molecular docking study revealed the highest binding affinity by ε-viniferin (3) (−9.9 kcal/mol) against topoisomerase II α. 3-Hydroxyisoagatholactone (2) and ε-viniferin (3) fulfilled Lipinski’s rule with no violation, and the organ toxicity predictions revealed that all the compounds showed no cytotoxicity and hepatotoxicity effects. Thus, this study’s combined in vitro and in silico outcomes suggest the potential use of the isolated compounds in drug discovery and support the traditional relevance of C. adenocaule.
9
Sergiy, Vlasov, Kovalenko Sergiy, Orlenko Inna, Zhuravel Iryna, Krolenko Konstantin, and Vlasov Vitaliy. "Synthesis and antimicrobial activity of 3-(2-N-(aryl,acyl)amino-5-methyl-1,3-thiazol-4-yl)-2H-chromen-2-ones." ScienceRise: Pharmaceutical Science, no. 6(28) (December 30, 2020): 50–55. https://doi.org/10.15587/2519-4852.2020.221701.
Full textAbstract:
<strong>The aim </strong>of this work is to study methods of 3-(2-N-(aryl,acyl)amino-5-methyl-1,3-thiazol-4-yl)-2H-chromen-2-ones preparation and their antimicrobial activity. <strong>Materials and methods. </strong><sup>1</sup>Н NMR spectra were recorded on Varian Mercury-200 (200 MHz), <sup>13</sup>C NMR spectra were acquired on Bruker Avance 500 <sup>1</sup>H NMR (500 MHz) and <sup>13</sup>C NMR (125 MHz) in DMSO-d<sub>6</sub> and CDCl<sub>3</sub>. LC-MS analysis of compounds was performed on an Agilent 1100 HPLC instrument with chemical ionization at atmospheric pressure (APCI). The study of antimicrobial activity of compounds was performed by agar well diffusion method. The docking studies were performed using Autodock Vina. <strong>Results and discussion. </strong>The interaction of 3-(2-bromopropanoyl)-2H-chromen-2-ones with N-substituted thioureas produced novel derivatives of 3-(2-N-(aryl,acyl)amino-5-methyl-1,3-thiazol-4-yl)chromen-2-ones. The study of antimicrobial activity of the obtained compounds allowed to identify active samples against E. сoli and P. aeruginosa strains. Among the tested compounds, 8-methoxy-3-{2-[(2-methoxyphenyl)amino]-5-methyl-1,3-thiazol-4-yl}-2H-chromen-2-one showed higher activity than the reference drug Streptomycin against E. coli strain. Some compounds showed high activity against P. aeruginosa. Docking studies of the synthesized compounds indicated that they can bind in the active site to bacterial tRNA (guanine37-N1)-methyltransferase. <strong>Conclusions. </strong>Novel derivatives of 2H-chromen-2-ones with 2-N-(aryl,acyl)amino-5-methyl-1,3-thiazol moiety at the position 3 were obtained by the Hantzsch thiazole synthesis starting from 3-(2-bromopropanoyl)-2H-chromen-2-ones. Studies of antimicrobial activity allowed to identify new 2H-chromen-2-one derivatives as equipotent antimicrobial agents to the reference drug Streptomycin or even more potent. The docking studies revealed that the synthesized compounds may be inhibitors of tRNA (guanine37-N1)-methyltransferase, which is a crucial enzyme for survival of different bacteria, e.g. P. aeruginosa during stress conditions
10
Pavlyukova, Yu N., L. M. Pevzner, P. A. Gukova, D. D. Novozhilova, G. G. Danagulyan та V. A. Ostrovskii. "β-(2R,3S,5R)-2-(hydroxymethyl)-6-(5-phenyl-<i>2Н</i>-tetrazole-2-yl) tetrahydro-<i>2Н</i>-piran-3,4,5-triol. Synthesis and computer prediction of biological activity". Translational Medicine 10, № 6 (2023): 495–506. http://dx.doi.org/10.18705/2311-4495-2023-10-6-495-506.
Full textAbstract:
Background. An urgent problem of creating a domestic production of modern medicines under the conditions of sanctions pressure is the molecular design and development of rational methods for the synthesis of active pharmaceutical ingredients of original drugs and young generics.Objective. In this work, a computer prediction of the biological activity of β-(2R,3S,5R)-2-(hydroxymethyl)-6-(5-phenyl-2H-tetrazole-2-yl) tetrahydro-2H- piran-3,4,5-triol 1 — compounds, in the molecule of which there are two promising pharmacophore fragments, was performed: tetrazolyl and galactopyranosyl. Both fragments of the studied molecule are actively used by leading scientific centers for the molecular design and synthesis of promising active pharmaceutical ingredients (API) of modern medicines.Design and methods. For this purpose, the latest versions of the PASS computer complex were used in combination with molecular docking and scoring in the AutoDoc Vina program.Results. Based on computer prediction data, it is shown that this compound may have multi-target biological activity.Conclusion. A rational, scalable method for the synthesis of compound 1, which is recommended for testing in vitro, in vivo activity, is proposed.
11
Thapa, Shankar, Shachindra L. Nargund, and Mahalakshmi Suresha Biradar. "Molecular Design and In-Silico Analysis of Trisubstituted Benzimidazole Derivatives as Ftsz Inhibitor." Journal of Chemistry 2023 (March 1, 2023): 1–9. http://dx.doi.org/10.1155/2023/9307613.
Full textAbstract:
Tuberculosis (TB) is the fastest spreading infectious disease and one of the top ten diseases that kill millions of people annually. The rapid spread of a multidrug-resistant strain of Mycobacterium tuberculosis leads to multidrug-resistance tuberculosis (MDR-TB), which is very difficult to treat. Filament temperature-sensitive protein ring-Z (Ftsz) protein could be the best target to inhibit bacterial cytokinesis. This research is conducted to predict the antitubercular activity of trisubstituted benzimidazole derivatives targeting FtsZ protein by an in-silico approach (molecular docking, pharmacokinetic parameter, drug likeliness, toxicity prediction, and biological activity prediction). Amine and aldehyde substitutions are used as primary scaffolds to design 20 trisubstituted benzimidazole derivatives for molecular docking. AutoDock vina v.1.2.0 software was used to predict the binding interaction between ligand and receptor (FtsZ, PDB ID : 1RQ7). The drug-likeliness properties and toxicity of ligands were predicted from SwissADMET and ToxiM web servers, respectively. Compound A15 (2,3,5,6-tetrafluoro-N1-{6-fluoro-5-[4-(1H-imidazole-1-yl) phenoxy]-1H-1,3-benzodiazol-2-yl} benzene-1,4-diamine) showed the best binding energy (ΔG = −10.2 kcal/mol/) along with four hydrogen bond interactions (GLY107, PHE180, ASP 184). Similarly, compounds A19 and A20 have the best binding score of −9.8 kcal/mol, with excellent pharmacokinetic parameters. It is found that the binding energy of all ligands (ΔG = −8.0 to −10.2 kcal/mol) is better than the reference compound Moxifloxacin (ΔG = −7.7 kcal/mol). None of the ligands violate Lipinski’s rule, but all ligands’ toxicity is slightly high (>0.8 score). It is reported that the amine-substituted benzimidazole derivatives have better binding energy than the aldehyde substitution. Therefore, it is concluded that compounds A19 and A20 can be the best candidate as Ftsz protein inhibitors but an in-vitro animal study and toxicity study are necessary to validate these data.
12
Tanbin, Suriyea, Fazia Adyani Ahmad Fuad, and Azzmer Azzar Abdul Hamid. "Virtual Screening for Potential Inhibitors of Human Hexokinase II for the Development of Anti-Dengue Therapeutics." BioTech 10, no. 1 (2020): 1. http://dx.doi.org/10.3390/biotech10010001.
Full textAbstract:
Dengue fever, which is a disease caused by the dengue virus (DENV), is a major unsolved issue in many tropical and sub-tropical regions of the world. The absence of treatment that effectively prevent further viral propagation inside the human’s body resulted in a high number of deaths globally each year. Thus, novel anti-dengue therapies are required for effective treatment. Human hexokinase II (HKII), which is the first enzyme in the glycolytic pathway, is an important drug target due to its significant impact on viral replication and survival in host cells. In this study, 23.1 million compounds were computationally-screened against HKII using the Ultrafast Shape Recognition with a CREDO Atom Types (USRCAT) algorithm. In total, 300 compounds with the highest similarity scores relative to three reference molecules, known as Alpha-D-glucose (GLC), Beta-D-glucose-6-phosphate (BG6), and 2-deoxyglucose (2DG), were aligned. Of these 300 compounds, 165 were chosen for further structure-based screening, based on their similarity scores, ADME analysis, the Lipinski’s Rule of Five, and virtual toxicity test results. The selected analogues were subsequently docked against each domain of the HKII structure (PDB ID: 2NZT) using AutoDock Vina programme. The three top-ranked compounds for each query were then selected from the docking results based on their binding energy, the number of hydrogen bonds formed, and the specific catalytic residues. The best docking results for each analogue were observed for the C-terminus of Chain B. The top-ranked analogues of GLC, compound 10, compound 26, and compound 58, showed predicted binding energies of −7.2, −7.0, and −6.10 kcal/mol and 7, 5, and 2 hydrogen bonds, respectively. The analogues of BG6, compound 30, compound 36, and compound 38, showed predicted binding energies of −7.8, −7.4, and −7.0 kcal/mol and 11, 9, and 5 hydrogen bonds, while the top three analogues of 2DG, known as compound 1, compound 4, and compound 31, showed predicted binding energies of −6.8, −6.3, and −6.3 kcal/mol and 4, 3, and 1 hydrogen bonds, sequentially. The highest-ranked compounds in the docking analysis were then selected for molecular dynamics simulation, where compound 10, compound 30, and compound 1, which are the analogues of GLC, BG6, and 2DG, have shown strong protein-ligand stability with an RMSD value of ±5.0 A° with a 5 H bond, ±4.0 A° with an 8 H bond, and ±0.5 A° with a 2 H bond, respectively, compared to the reference molecules throughout the 20 ns simulation time. Therefore, by using the computational studies, we proposed novel compounds, which may act as potential drugs against DENV by inhibiting HKII’s activity.
13
Rajapaksha, HKK, MN Fernando, NRM Nelumdeniya, AWMKK Bandara, and ARN Silva. "Evaluation of In vitro anti-inflammatory activity and In-silico pharmacokinetics and molecular docking study of Horsfieldia iryaghedhi." Journal of Phytopharmacology 13, no. 2 (2024): 143–53. http://dx.doi.org/10.31254/phyto.2024.13208.
Full textAbstract:
Background: Phytochemicals are still a valuable source to develop clinically important drugs in treating chronic and acute diseases. Inflammation is a response to an injurious stimulus of the body and novel therapeutic agents are needed to alleviate the condition with minimum side effects. Aims and Objectives: To investigate in vitro anti-inflammatory activity of methanol and aqueous leaf, bark, and combination extracts of plant Horsfieldia iryaghedhi by heat-induced egg albumin denaturation method and to analyze the phytochemicals of Horsfieldia iryaghedhi for their anti-inflammatory potential against cyclooxygenase- 2 (COX-2) using molecular docking. Methodology: Matured and fully expanded fresh leaves and barks of H. iryaghedhi were collected, and the extractions were obtained cold maceration using 99.9% methanol and distilled water as solvents. A concentration series was then developed, and the anti-inflammatory activity was evaluated against Diclofenac sodium as the positive control, using the heat-induced egg albumin denaturation method. Further, selected phytochemicals were tested against COX-2 enzyme (PDB ID: 5IKR) using site-specific molecular docking with autodock vina and the binding energies and pharmacokinetic and toxicity parameters were evaluated. Results: The methanol and aqueous extracts have shown a moderate to strong concentration-dependent anti-inflammatory activity with reference to standard Diclofenac sodium (IC50 116.4 μg/ml) and Methanol bark extract exhibited potent anti-inflammatory activity compared to other extracts (IC50 293 μg/ml). Further, Methanol and aqueous extracts showed a statistically significant correlation between concentration and percentage inhibition (p<0.05, R2 ≈1). The molecular docking results suggest that the phytochemicals available on the plant have possible COX-2 inhibitory activity and the compounds selected (Methyl 2,4-dihydroxy-6-methylbenzoate and N, N-Dimethyl-5-methoxy tryptamine) even got favourable toxicity and pharmacokinetic parameters confirming their drugability. Conclusion: Methanol bark extract of Horsfieldia iryaghedhi have marked in vitro anti-inflammatory activity. The results indicate a solid possibility of lead discovery of anti- inflammatory agents from the bark and leaves of Horsfieldia iryaghedhi. However, further molecular dynamics studies and in vivo tests may be required to confirm the findings.
14
Safithri, Mega, Eko Budi Koendhori, Dimas Andrianto, et al. "Analysis of Bioactive Compounds Piper crocatum as Inhibitors of Acetylcholinesterase In Silico and In Vitro." Trends in Sciences 22, no. 4 (2025): 9437. https://doi.org/10.48048/tis.2025.9437.
Full textAbstract:
Alzheimer’s disease, the leading cause of dementia in older adults, involves memory loss and cognitive decline, with β-amyloid plaques and neurofibrillary tangles (NFTs) as key features. Acetylcholinesterase (AChE), an enzyme that breaks down acetylcholine, plays a role in the formation of these plaques and tangles. AChE is a promising target for the development of small molecule inhibitors in Alzheimer’s disease (AD) treatment. Indonesia’s native red betel (Piper crocatum) contains bioactive compounds that inhibit AChE activity, as shown in previous research. This study aims to evaluate the AChE inhibitory potential of bioactive compounds from P. crocatum extracts (water, n-hexane and ethyl acetate) using an in silico approach (molecular docking) with 3 different docking software programs. Donepezil served as the reference compound, and the results were compared with in vitro AChE inhibition assays. The potential AChE inhibitors, based on molecular docking using PyRx, Autodock Vina and YASARA Structure, from each extract are SM05 (n-hexane extract), SM15 (water extract) and SM18 (ethyl acetate extract), with the most negative ΔGbind values, measuring −8.8, −9.2 and −11.2 kcal/mol (more negative than Donepezil’s ΔGbind values). SM15 and SM18 Compounds show promise, based on its ΔGbind values, interactions with AChE, favorable pharmacokinetic properties, bioavailability, bioactivity and toxicity positioning both compounds as strong candidates for AD therapy. Both compounds were docked to the AChE substrate binding pockets (6O4W), forming hydrogen bonds with His447 and Phe297 at the “gorge” active site, and hydrophobic interactions with key amino acids in the peripheral anionic site (PAS) and substrate-binding sites (Tyr124, Phe297 and Phe338). This is consistent with in vitro assay results, which show that the ethyl acetate extract has strong inhibition, with an IC50 of 16.7908 ppm, while the water infusion extract yields a 26.621 % inhibition of AChE enzyme activity. In addition, the DIY extract exhibited the strongest AChE inhibitory activity with an IC50 of 40.799 ppm. HIGHLIGHTS Piper crocatum (red betel leaf) shows potential as a natural acetylcholinesterase (AChE) inhibitor, with compounds SM05 (2-(3,4-Dimethoxyphenyl)-6-ethoxy-7-methoxy-1-naphthol), SM15 (Columbin) and SM18 (Flemiphilippinin A) identified as promising candidates through in silico molecular modeling, as indicated by the most negative binding free energy values generated through 3 molecular docking methods (Virtual Screening with PyRx, Autodock Vina and YASARA Structure), especially compound SM18 (Flemiphilippinin A) from ethyl acetate extract (−11.2 kcal/mol). This aligns with the in vitro assay results, which show that the ethyl acetate extract has the strong inhibition, with an IC50 of 16.7908 ppm, as provided by Nurinsani et al. [10]. The red betel leaves water extract from DIY exhibited the most potent acetylcholinesterase (AChE) inhibitory activity with the lowest IC50 value (40.799 ppm), highlighting the significant inhibitory activity of the extract. Flemiphilippinin A (SM18) showed the strongest binding affinity to AChE (ΔGbind −2 kcal/mol), supported by favorable pharmacokinetic properties and bioavailability, as indicated by the fulfillment of Lipinski’s Rule of 5, ADME and bioactivity scores. It acts as a Nuclear receptor ligand (0.53), while Columbin (SM15) exhibits bioactivity as a Nuclear receptor ligand [0.66] and as an Enzyme inhibitor (0.57), suggesting that both compounds have potential as therapeutic candidates for Alzheimer’s disease (AD). Virtual screening and molecular docking revealed robust interactions of SM05, SM15 and SM18 with critical AChE active site residues, indicating their capability to inhibit AChE activity and potentially prevent AD progression. The 3 compounds from red betel leaf fractions are safe and have potential as oral drugs for Alzheimer’s therapy, with oral toxicity similar to donepezil (toxicity class IV, LD50 505 mg/kg) based on ProTox3 Prediction (with toxicity class IV for SM15, toxicity class V for SM05 and SM18). Pharmacokinetic evaluation confirmed the 3 compounds met Lipinski’s rule of 5 and showed high gastrointestinal absorption, with SM15 excelling in drug-likeness and bioactivity parameters critical for AD therapy. GRAPHICAL ABSTRACT
15
Pires, Y. M. D. S., J. T. Ciecilinsky, L. D. S. Gomes, F. D. A. Oliveira, and F. R. D. C. Almeida. "POS0498 MOLECULAR DOCKING AND PHARMACOLOGICAL ANALYSIS OF ALPHA-PHELLANDRENE IN CHRONIC PAIN: THE ROLE OF SEROTONINERGIC SYSTEM." Annals of the Rheumatic Diseases 81, Suppl 1 (2022): 503.1–503. http://dx.doi.org/10.1136/annrheumdis-2022-eular.1652.
Full textAbstract:
BackgroundPain is an unpleasant sensory and emotional experience that causes human suffering.1 Its prevalence has increased, as well as the abuse and dependence on strong opioids.2,3 The α-phellandrene is a terpene that exerts antinociceptive and immunostimulant effects,4 however, its mechanisms remain to be elucidated. In this way, bioinformatics may assist in developing new therapeutic approaches for pain management.ObjectivesTo investigate the action of a-PHEL in chronic pain, focusing on the role of the serotoninergic system, to develop a new therapeutic tool without the side effects of conventional drugs.MethodsMolecular docking is an important method for the investigation of the mechanism of action of natural compounds. It is possible to evaluate the molecular dynamics, elucidating the stability of complexes. The software PyMOL and AutoDock Vina 1.5.7 were used to predict interactions of a-PHEL and 5-HT2AR.The mechanism of action of a-PHEL in chronic pain was analyzed in vivo as well. The Ethics Committee of UFPI approved this project (protocol n° 305/17). Female Swiss mice (25-30 g) underwent partial sciatic nerve ligation surgery to induce neuropathy. The neuropathic mice (N=6) were pre-treated with 5-HT2A receptor antagonist Ketanserin (0,3 mg/kg, i.p.) or Saline (10 mL/kg, p.o.). After 20min, they were treated with α-phel (6,25 mg/kg, p.o.) and after 1h they were evaluated by the Von Frey test.ResultsThe serotoninergic system has a complex and important role in pain modulation especially through descending inhibitory pathways. The Molecular docking predicted the positioning of a-PHEL in the 5-HT2AR, aiding the understanding of its biological activity. The analysis identified 9 key positions for the ligand binding in 5-HT2AR. The lowest Gibbs free energy ΔG= -6.9 kcal/mol. The negative binding energy indicates a strong and stable bond, therefore, α-PHEL has a high affinity for the receptor (Figure 1).Figure 1.Graphical 3D representation of the binding mode of α-PHEL with 5-HT2AR. A - The ligand (orange) is shown surrounded by a molecular surface of the receptor (green). B – Representation of the best-scoring docked pose (-6.9 kcal/mol) of a-PHEL (orange).Excellent in vivo therapeutic effects were observed in the animal model of neuropathic pain. Regarding the pharmacological in vivo analysis, the a-PHEL significantly decreased the pain threshold (P<0.05), exhibiting an anti-hypersensitive effect. The inhibition of serotonergic transmission by pretreatment with Ketanserin significantly reduced the antinociceptive effect of a-PHEL in mice.The data indicate that a-PHEL exerts its antinociceptive effect on chronic neuropathic pain model by activation of the 5-HT2AR receptor. Its analgesic effect seems to be mediated by descending inhibitory serotonin system interfering with pain impulse transduction.ConclusionChronic pain is often resistant to medical treatment and the cheminformatics techniques may facilitate the discovery of new compounds, guiding towards specific molecular targets.The a-PHEL may act as a serotoninergic agonist, reducing mechanical sensitivity. It is a promising compound for chronic pain treatment, with lower cost and fewer adverse effects than opioids. Future investigations are expected to highlight the in-depth effects of the interaction of a-PHEL with other receptor subtypes.References[1]Raja SN, et al. The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises. Pain. 2020;161(9):1976-1982.[2]Xie J, et al. Temporal trends of opioid use among incident osteoarthritis patients in Catalonia, 2007-2016: a population-based cohort study. Annals of The Rheumatic Disease. 2020; 79 (sl. 1): 174.[3]Liktor-Busa E, et al. Analgesic Potential of Terpenes Derived from Cannabis sativa. Pharmac Rev. 2021, 73(4):98-126.[4]Pinheiro FR, et al. α-Phellandrene exhibits antinociceptive and tumor-reducing effects in a mouse model of oncologic pain. Tox Appl Pharmacol. 418(1), 2021Disclosure of InterestsNone declared.
16
Diyan, Diyan Sakti Purwanto, Hari Susanti, and Nining Sugihartini. "MOLECULAR DOCKING AS POTENTIAL ANTI-INFLAMMED QUERSETIN OF MORINGA LEAVES (Moringa oleifera L.) WITH AUTODOCK-VINA." Jurnal Ilmiah Manusia Dan Kesehatan 4, no. 2 (2021): 309–13. http://dx.doi.org/10.31850/makes.v4i2.818.
Full textAbstract:
Inflammation is a response to tissue injury that involves a physiological process in the form of activation of the cyclooxygenase (COX) enzyme which has two isoforms, namely the cyclooxygenase-1 (COX-1) and cyclooxygenase-2 (COX-2) enzymes. The leaves of Moringa (Moringa oleifera L.) contain quercetin which has shown anti-inflammatory activity by blocking the synthesis and release of histamine and other inflammatory allergic mediators. This study aims to determine the role of quercetin in Moringa leaves as an anti-inflammatory ligand 6 COX cyclooxigenase-2 (COX-2) with the application of autodock vina. The method used was that all ligands were docking molecularly using the AutoDock Vina program. The results obtained are the binding affinity (kcal / mol) of the ligand to protein. The Ligplot + program is used to visualize the 3D conformation of molecules and ligand-protein interactions. The hardware used by ASUS notebooks with Windows 10 64 bit specifications. Based on molecular docking, quercetin has a potential activity as an anti-inflammatory because it has affinity and forms hydrogen cox 6 bonds in-silico and can be continued with in vitro activity tests in the laboratory to get results as anti-inflammatory.
17
Sun, Xiuling, Zhiwei Jiang, Qihua Wang, Wenjie Hu, and Litao Zhang. "Investigating the active components and molecular mechanism of alpinia officinarum hance therapy against depression by network pharmacology and molecular docking combined with neuroprotective effects in PC12 cells." Arabian Journal of Chemistry 18 (April 10, 2025): 272024. https://doi.org/10.25259/ajc_27_2024.
Full textAbstract:
Depression is a common chronic mood-related disorder characterized by depressed mood, loss of interest, and fatigue. Extract from alpinia officinarum hance (AOH) has shown anti-depressant properties in Bagg Albino/C (BALB/c) mice with depression induced by chronic unanticipated stress. However, the molecular mechanisms underlying the anti-depressant effects of AOH remained unclear. The active ingredients of AOH were acquired via the Traditional Chinese Medicine Systems Pharmacology database and analysis platform (TCMSP), and their corresponding targets were collected from the high-throughput experiment- and reference-guided database of traditional Chinese medicine (HERB). Moreover, the targets associated with depression were identified using the GeneCards database. Common targets between the databases were identified as the anti-depressant targets of AOH. The Search Tool for the Retrieval of Interacting Genes/Proteins (STRING) was used to build the Protein-Protein Interaction (PPI) network. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway and Gene Ontology (GO) enrichment analyses were performed using Database for Annotation, Visualization, and Integrated Discovery (DAVID). Using AutoDock Vina and PyMOL software, molecular docking technology was employed to verify whether the main active components in AOH could bind to central targets. Finally, the CCK8 assay was used to analyze the activity of AOH extract on PC12 cells and depression model cells induced by corticosterone (CORT). The expression was checked via the Quantitative Real - Time Polymerase Chain Reaction (qRT-PCR) of key target molecules. After a successful screening of 10 active components in AOH, it was demonstrated that these compounds had strong relationships with 115 targets associated with depression, among which Interleukin - 6 (IL6), RAC - alpha serine/threonine - protein kinase (AKT1), Interleukin - 1 beta (IL1B), tumor necrosis factor (TNF), Epidermal Growth Factor Receptor (EGFR), and Tumor protein p53 (TP53) could be the potential targets for treating depression. GO and KEGG enrichment pathway analysis yielded 416 terms and 153 pathways, respectively. Quercetin, kaempferol, sitosterol, medicarpin, and galangin were the key active components of AOH involved in treating depression. Molecular docking indicated the screened target proteins had good binding activity with active components with affinity values < 5 kcal/mol. AOH extract was non-cytotoxic to PC12 cells and had a good protective effect on the depression cell model. The qRT-PCR analysis showed that the AOH extract can restore EGFR, TP53, and IL1B levels in CORT-induced PC12 cells to normal. Totally Quercetin, kaempferol, sitosterol, medicarpin, and galangin were identified as possible active ingredients in AOH that could potentially treat depression. The antidepressant benefits of AOH may stem from its capacity to modulate neuroinflammation.
18
Zhang, Huyang, and Wenjuan Hou. "The Investigation of LPA Binding Sites on LPA 1 And LPA 4." Highlights in Science, Engineering and Technology 45 (April 18, 2023): 151–59. http://dx.doi.org/10.54097/hset.v45i.7337.
Full textAbstract:
Lysophosphatidic acid (LPA) is a class of biologically active lipid molecules with important biological functions. LPA can induce various cellular responses through six LPA receptors (LPA1-6) on cell membranes to achieve its biological functions. This study utilized computer simulation tools such as AutoDock Vina and RosettaFold to investigate the binding sites of LPA1 and LPA4 to LPA molecules. Based on these results, this study could provide new insights for the subsequent development of extracellular antagonists and agonists, and facilitate drug formation for the treatment of cancer invasion.
19
Lokesh, D., and R. M. R. Charan. "Comparative Study of Molecular Interactions of Thymol and B4S with Kinesin-5 In-Silico for the Selective Anti-cancer Activity of Thymol." CARDIOMETRY, no. 25 (February 14, 2023): 1654–60. http://dx.doi.org/10.18137/cardiometry.2022.25.16541660.
Full textAbstract:
Aim: To study the comparative molecular interactions of Thymol and 3’-fluoro-4’-(trifluoromethyl)biphenyl-4-sulfonamide (B4S) with the active sites of Kinesin-5 protein using molecular docking analysis for the selective anti-cancer activity. Materials and Methods: In this study, Group 1 is the binding affinity of B4S with Kinesin-5 protein and Group 2 is the binding affinity of Thymol with Kinesin-5 protein. The sample size was calculated with a pretest power of 80%. The sample size per group is 10 and the total sample size is 20. The protein structure of Kinesin-5 protein was collected from the protein data bank (PDB) website and the ligand structures were collected from the NCBI-PubChem website. The binding energy (kcal/mol) was calculated using Autodock Vina Software.The structure of the protein was obtained from the PDB (protein data bank) database and the structures of ligand were obtained from the NCBI-PubChem database. The binding energy (kcal/mol) was calculated using Novel Autodock Vina Software. Results: The mean binding affinity of Thymol (-7.89 kcal/mol) was significantly (p=0.007, p<0.05, 2-tailed t-test) higher than the standard inhibitor B4S (-7.19 kcal/mol) towards the active sites of Kinesin-5 protein. Conclusion: The results suggest that thymol may bind selectively to the cancerous cells and inhibit their proliferation and can act as a novel anti-cancer agent.
20
Saji, Christy, Rajeswary K. Balachandran, Aneeza M. Nizar, et al. "MOLECULAR DOCKING STUDIES WITH PHYTOCONSTITUENTS OF TINOSPORA SINENSIS TARGETING SARS-COV-2 PROTEIN USING AUTODOCK VINA." INDIAN DRUGS 62, no. 05 (2025): 22–27. https://doi.org/10.53879/id.62.06.15489.
Full textAbstract:
Drug discovery is time-consuming and resource-intensive, but computational approaches offer a more efficient alternative. The urgency for antiviral treatments became evident during the SARS-CoV-2 pandemic due to the virus’s rapid spread and mutations. This study utilizes computational drug design techniques to assess the antiviral potential of Tinospora sinensis constituents against the SARS-CoV-2 main protease (PDB ID: 6LU7). The target protein was prepared using AutoDock tools, and molecular docking was conducted with AutoDock Vina. Of 37 compounds, 5 exhibited a binding affinity below -7 kcal mol-1, with tinosporaside showing the highest affinity and low toxicity. These results suggest that tinosporaside is a promising candidate for further development. By streamlining drug discovery, computational methods accelerate the identification of potential treatments, reducing costs and waste. This study underscores the value of computational methods in antiviral research and supports further investigation into combating SARS-CoV-2 and future viral threats.
21
Adeoye, Moriam Dasola, Abel Kolawole Oyebamiji, Mojeed Ayoola Ashiru, Rasheed Adewale Adigun, Olabisi Hadijat Olalere, and Banjo Semire. "Biological evaluation of selected metronidazole derivatives as anti-nitroreductase via in silico approach." Ecl�tica Qu�mica Journal 47, no. 4 (2022): 27–36. http://dx.doi.org/10.26850/1678-4618eqj.v47.4.2022.p27-36.
Full textAbstract:
The 1-(2-hydroxyethyl)-2-methyl-5-nitroimidazole (2HMN) is a powerful antibacterial and antiparasitic drug used alongside other drugs against Helicobacter pylori infection and was investigated the effects of substituents: –OH (A), H (B), –SPh (C), –COOH (D), –NO2 (E) and –OCH3 (F) on the interactions of 2HMN with the target nitroreductase Rdxa protein for the treatment of the infection. Spartan 14 (optimization), PyMOL 1.7.4.4 (to treat downloaded protein), Autodock Tool (locate protein binding site), Autodock vina 1.1.2 (docking calculation) were used to discover the nonbonding interaction between docked complexes using SWISSADME and Pre-ADMET software. The band gaps order for the studied compounds were C < A < F < B < D < E, a probability of highest charge distribution and activity for SPh substituted derivatives and the ligands conformed to the Lipinski’s rule of five. Compounds D and E are noninhibitors and nonsubstrate for cytochrome P450 2C9, P450 2D6, P450 2C19 with the same efficient calculated binding affinity (–21.3 kJ mol–1) and inhibition constant (7.8) comparable to the standard compound A.
22
Omer, Ejlal A., Sara Abdelfatah, Max Riedl, Christian Meesters, Andreas Hildebrandt, and Thomas Efferth. "Coronavirus Inhibitors Targeting nsp16." Molecules 28, no. 3 (2023): 988. http://dx.doi.org/10.3390/molecules28030988.
Full textAbstract:
During the past three decades, humans have been confronted with different new coronavirus outbreaks. Since the end of the year 2019, COVID-19 threatens the world as a rapidly spreading infectious disease. For this work, we targeted the non-structural protein 16 (nsp16) as a key protein of SARS-CoV-2, SARS-CoV-1 and MERS-CoV to develop broad-spectrum inhibitors of nsp16. Computational methods were used to filter candidates from a natural product-based library of 224,205 compounds obtained from the ZINC database. The binding of the candidates to nsp16 was assessed using virtual screening with VINA LC, and molecular docking with AutoDock 4.2.6. The top 9 compounds were bound to the nsp16 protein of SARS-CoV-2, SARS-CoV-1, and MERS-CoV with the lowest binding energies (LBEs) in the range of −9.0 to −13.0 kcal with VINA LC. The AutoDock-based LBEs for nsp16 of SARS-CoV-2 ranged from −11.42 to −16.11 kcal/mol with predicted inhibition constants (pKi) from 0.002 to 4.51 nM, the natural substrate S-adenosyl methionine (SAM) was used as control. In silico results were verified by microscale thermophoresis as in vitro assay. The candidates were investigated further for their cytotoxicity in normal MRC-5 lung fibroblasts to determine their therapeutic indices. Here, the IC50 values of all three compounds were >10 µM. In summary, we identified three novel SARS-CoV-2 inhibitors, two of which showed broad-spectrum activity to nsp16 in SARS-CoV-2, SARS-CoV-1, and MERS-CoV. All three compounds are coumarin derivatives that contain chromen-2-one in their scaffolds.
23
Fajrin, Fifteen Aprila, Agung Endro Nugroho, Rina Susilowati, and Arief Nurrochmad. "Molecular Docking Analysis of Ginger Active Compound on Transient Receptor Potential Cation Channel Subfamily V Member 1 (TRPV1)." Indonesian Journal of Chemistry 18, no. 1 (2018): 179. http://dx.doi.org/10.22146/ijc.28172.
Full textAbstract:
Ginger had been reported to ameliorate painful diabetic neuropathy (PDN) in an animal model. Gingerol and shogaol were active compounds of ginger that potentially act on transient receptor potential cation channel subfamily V member 1 (TRPV1), a key receptor in PDN. This study aims to predict the binding of gingerol and shogaol to TRPV1 using an in silico model. The ligands of the docking study were 3 chemical compounds of each gingerol and shogaol, i.e. 6-shogaol, 8-shogaol, 10-shogaol, 6-gingerol, 8 gingerol and 10-gingerol. Capsaicin, a TRPV1 agonist, was used as a native ligand. The TRPV1 structure was taken from Protein Data Bank (ID 3J9J). The docking analysis was performed using Autodock Vina. The result showed that among the ginger active compounds, 6-shogaol had the strongest binding energy (-7.10 kcal/mol) to TRPV1. The 6-shogaol lacked the potential hydrogen bond to Ile265 of TRPV1 protein, which capsacin had. However, it's binding energy towards TRPV1 was not significantly different compared to capsaicin. Therefore, 6-shogaol had potential to be developed as a treatment for PDN.
24
Panchal, Viswaskumar, Zakirhusen Gadhawala, Arun Malaviya, and Shreekant Prajapati. "Synthesis, Characterization and In Silico Studies of Novel (E)-4-(((3-(substituted phenyl)-1-phenyl-1H-pyrazol-5-yl)methylene)amino)benzenesulfonamide as Diuretic Agents." Oriental Journal Of Chemistry 40, no. 2 (2024): 413–21. http://dx.doi.org/10.13005/ojc/400212.
Full textAbstract:
This research delves into the examination of benzene sulphonamide derivatives featuring pyrazole rings as potential diuretics. Concentrating on their role as human carbonic anhydrase inhibitors (hCA), the investigation aims to unveil a groundbreaking diuretic drug. Six innovative benzenesulfonamide derivatives are synthesized utilizing a conventional heating process. Subsequently, employing AutoDock Vina 1.2.3, these compounds undergo molecular docking assessments and pharmacokinetic predictions at the active sites of hCA I and hCA II, while the SwissADME program is employed for pharmacokinetic forecasting. Notably, Compounds 17 and 19 exhibit robust binding affinities with hCA I and II, respectively, as evidenced by the docking study. ADME studies reveal favorable bioavailability and adherence to PAINS alerts, as well as Lipinski's rule of five requirements. Consequently, based on the findings, these compounds exhibit significant potential as diuretics in comparison to well-established acetazolamide medications.
25
Aziz, Husna Abdul, Yeremiah Rubin Camin, and Vivitri Dewi Prasasty. "Therapeutic Potential of Quercetin Derivatives: In Silico Investigation of HIV-1 Protease Inhibition." Journal of Tropical Biodiversity 4, no. 2 (2024): 67–82. http://dx.doi.org/10.59689/bio.v4i2.215.
Full textAbstract:
Human Immunodeficiency Virus (HIV) type 1 is the predominant strain known for its impact on the immune system and its propensity for mutation. According to the World Health Organization (WHO), the global infection count reached 37.9 million in 2018, with alarming rates of mortality and morbidity. Ongoing drug discovery endeavors encompass various facets, including investigations into HIV protease—a key enzyme in the cleavage process of gag and gag-pol polyprotein chains essential for the genesis of new virions. While numerous studies suggest the inhibitory potential of quercetin against HIV-1, comprehensive exploration regarding its interaction with the HIV-1 protease receptor remains limited. This study aimed to elucidate the therapeutic potential of quercetin derivative compounds as viable candidates for HIV protease inhibition. Employing in silico analysis, molecular docking of 36 quercetin derivative compounds with the HIV-1 protease receptor (code 3SO9) using the Pyrx-Autodock Vina-Open Babel platform was conducted. Prior to docking, ligand preparation was meticulously performed using Autodock Tools 1.5.6, with geometry optimization utilizing Avogadro software. The interaction was assessed through Gibbs free energy (∆G) scoring, where a more negative ∆G value indicated a stronger binding propensity between the ligand and receptor. The docking results revealed that 22 quercetin derivative compounds exhibited Gibbs energy (∆G) values lower than the original ligand, darunavir. However, 5 compounds deviated from Lipinski's rule, while 17 compounds adhered to Lipinski's criteria. Consequently, these 17 quercetin derivative compounds exhibit promising potential as candidate drugs for HIV-1 protease inhibition.
26
Frimayanti, Neni, Enda Mora, and Rizki Anugrah. "Study of Molecular Docking of Chalcone Analoque Compound as Inhibitors for Liver Cancer Cells HepG2." Computer Engineering and Applications Journal 7, no. 2 (2018): 147–58. http://dx.doi.org/10.18495/comengapp.v7i2.260.
Full textAbstract:
Molecular docking study using chalcone analogue compounds with proteins target from modeling crystallographic structure of Tyrosine kinase enzymes with code 1T46 was carried out with the aid of a computer using the AutoDock Vina program. The aim this study to determine the activity of 5 chalcone analogue compounds obtained from previous studies and 3 chalcone analogues which were modified as inhibitors of liver cancer using 5-fluorouracil as a positive control. Based on the docking results, it has been carried out and shown those compounds 1, 2, and 3 have the potential as the active inhibitors againts HepG2 liver cancer with a successive affinity of -10.1 kcal/mol, -9.7 kcal/mol, and - 9.6 kcal/mol, respectively. For the modified chalcone analogue compounds, compound 8 has the best results with an affinity value of -8.3 kcal/mol and this compound also has six amino acid residues which are the same as 5-flourouracyl (i.e. positive control).
27
Lin, Ying-Tong, Xiao-Wei Yao, Zheng-Wu Luo, et al. "Polyketides with Cardioprotective Bioactivities from Sponge-Associated Fungus Aspergillus giganteus MA46-5." Molecules 30, no. 7 (2025): 1632. https://doi.org/10.3390/molecules30071632.
Full textAbstract:
One pair of novel enantiomers, gigantdioxin A (+)-1 and B (−)-1, with a skeleton of benzo[d][1,3]dioxin; a new acetophenone gigantone A (3); a known 3-chlorogentisyl alcohol (2), which is the bioprecursor of 1; acetophenone (4); and chromone derivative (5) were obtained from the sponge-associated fungus Aspergillus giganteus MA46-5. Their structures were established by extensive and in-depth spectral analysis, such as UV, 1D and 2D NMR, and HRESIMS. The absolute configurations of (±)-1 were deduced by ORD, chiral separation, and experimental and computational ECD. Meanwhile, we proposed a possible biosynthetic pathway of (±)-1. Fortunately, the pathway was proved by biomimetic synthesis through 2, as a bioprecursor, reacted with n-butyraldehyde. Myocardial protection assays showed that 3 and 4 possessed stronger protective effects than a positive control against myocardial cell H9c2 ischemia–reperfusion injury in low concentrations, and the effect of (−)-1 was almost equal to that of the positive control. Further, we explored the possible mechanism of myocardial protection through network pharmacology. Adenosine A2a receptor (ADORA2A) and serum albumin (ALB) represent potential targets for myocardial protection associated with (−)-1 and 4, respectively. Based on the network pharmacology, we docked the predicted proteins with bioactive compounds using Autodock Vina.
28
Dahikar, Girish D., and Rajendra O. Ganjiwale. "Synthesis and molecular docking of some new quinazoline analogues as anticonvulsants." INDIAN JOURNAL OF HETEROCYCLIC CHEMISTRY 35, no. 02 (2025): 487. https://doi.org/10.59467/ijhc.2025.35.487.
Full textAbstract:
Two series of new compounds, namely, 6-substituted-2-ethyl-3-(6-substituted-benzothiazol-2-yl)-3H-quinazolin-4-ones (De1-De10) and 6-substituted-2-ethyl-3-(pyridin-4-yl-formamide)-3H-quinazolin-4-ones (Ee1-Ee2) were prepared by condensing 6-substituted-2-ethyl-4-oxo-4H-3,1-benzoxazines (A1-2) with 6-substituted-2-aminobenzothiazoles (B1-5) and hydrazide of isonicotinic acid (C), respectively. The anticonvulsant activity of six derivatives was assessed against the Maximal Electroshock induced convulsions model in albino mice. All compounds were administered by the intraperitoneal route at a dose of 20 mg/kg body weight and TD50, ED50, and PI values were determined. Among the tested compounds, the compounds (De4, De8, De10) possessing electron-withdrawing groups (NO2, Br) exhibited better potency than the compounds bearing electron-releasing groups. The activity was confirmed to be significant at P &lt; 0.05 with respect to the standard drug diazepam. Similarly, the compounds (De4, De7, De8, De9, and De10) bearing electron-withdrawing groups (NO2, Br) showed good docking score against the protein 6X3X. The docking study was executed using AutoDock Vina software.. KEYWORDS :Anticonvulsant, Quinazoline, Benzothiazole, 6X3X protein and maximal electroshock.
29
Anderson, Shane D., Asna Tabassum, Jae Kyung Yeon, et al. "In silico prediction of ARB resistance: A first step in creating personalized ARB therapy." PLOS Computational Biology 16, no. 11 (2020): e1007719. http://dx.doi.org/10.1371/journal.pcbi.1007719.
Full textAbstract:
Angiotensin II type 1 receptor (AT1R) blockers (ARBs) are among the most prescribed drugs. However, ARB effectiveness varies widely, which may be due to non-synonymous single nucleotide polymorphisms (nsSNPs) within the AT1R gene. The AT1R coding sequence contains over 100 nsSNPs; therefore, this study embarked on determining which nsSNPs may abrogate the binding of selective ARBs. The crystal structure of olmesartan-bound human AT1R (PDB:4ZUD) served as a template to create an inactive apo-AT1R via molecular dynamics simulation (n = 3). All simulations resulted in a water accessible ligand-binding pocket that lacked sodium ions. The model remained inactive displaying little movement in the receptor core; however, helix 8 showed considerable flexibility. A single frame representing the average stable AT1R was used as a template to dock Olmesartan via AutoDock 4.2, MOE, and AutoDock Vina to obtain predicted binding poses and mean Boltzmann weighted average affinity. The docking results did not match the known pose and affinity of Olmesartan. Thus, an optimization protocol was initiated using AutoDock 4.2 that provided more accurate poses and affinity for Olmesartan (n = 6). Atomic models of 103 of the known human AT1R polymorphisms were constructed using the molecular dynamics equilibrated apo-AT1R. Each of the eight ARBs was then docked, using ARB-optimized parameters, to each polymorphic AT1R (n = 6). Although each nsSNP has a negligible effect on the global AT1R structure, most nsSNPs drastically alter a sub-set of ARBs affinity to the AT1R. Alterations within N298 –L314 strongly effected predicted ARB affinity, which aligns with early mutagenesis studies. The current study demonstrates the potential of utilizing in silico approaches towards personalized ARB therapy. The results presented here will guide further biochemical studies and refinement of the model to increase the accuracy of the prediction of ARB resistance in order to increase overall ARB effectiveness.
30
Pavlova, V. V., P. V. Zadorozhnii, V. V. Kiselev, A. V. Kharchenko, and O. V. Okhtina. "Modeling of new potential inhibitors of dihydrofolate reductase based on 1,3,4-thiadiazole amidoalkyl derivatives." Voprosy Khimii i Khimicheskoi Tekhnologii, no. 5 (October 2023): 91–97. http://dx.doi.org/10.32434/0321-4095-2023-150-5-91-97.
Full textAbstract:
Derivatives of 1,3,4-thiadiazole are very important for medical chemistry and pharmacy as potential drug substances. In this work, we carried out molecular docking studies of amidoalkyl derivatives of 1,3,4-thiadiazole: N-(2,2,2-trichloro-1-((5-aryl-1,3,4-thiadiazol-2-yl)amino)ethyl)carboxamides and N-(2,2,2-trichloro-1-((5-(arylamino)-1,3,4-thiadiazol-2-yl)amino)ethyl)carboxamides with dihydrofolate reductase (DHFR). The AutoDock Vina program based on the PyRx 0.8 platform was used for docking. Before docking, the enzyme structure (PDB ID: 1DLS) was prepared using the Chimera 1.14 program, and the structures of potential inhibitors and reference preparations were optimized by the PM3 method in the ArgusLab 4.0.1 program. According to the results of molecular docking, the analyzed compounds effectively interact with the active site of DHFR. It is shown that the introduction of an NH group between the 1,3,4-thiadiazole and aromatic rings leads to stronger binding of ligands to DHFR. Based on the results of molecular docking, the following hit compounds were selected: 4-methyl-N-(2,2,2-trichloro-1-((5-(phenylamino)-1,3,4-thiadiazol-2-yl)amino)ethyl)benzamide and 4-methyl-N-(2,2,2-trichloro-1-((5-(p-tolylamino)-1,3,4-thiadiazol-2-yl)amino)ethyl)benzamide, which are superior to the reference compounds according to the strength of the formed complex.
31
Cai, Meng, Yongjing Xiang, Zhengsheng Li, Juan Xie, and Fulong Wen. "Network pharmacology and molecular docking predictions of the active compounds and mechanism of action of Huangkui capsule for the treatment of idiopathic membranous nephropathy." Medicine 102, no. 37 (2023): e35214. http://dx.doi.org/10.1097/md.0000000000035214.
Full textAbstract:
Background: Huangkui Capsule is a single herbal concoction prepared from the flower of Abelmoschus manihot, which is used to treat idiopathic membranous nephropathy (IMN), a frequent pathologically damaging kidney condition. It has been widely utilized to treat a variety of renal disorders, including IMN, in clinical practice. However, the active compounds and mechanism of action underlying the anti-IMN effects of Huangkui Capsule remain unclear. In this study, we aimed to predict the potential active compounds and molecular targets of Huangkui Capsule for the treatment of IMN. Methods: The possible active components of Huangkui were located using the SymMap v2 database. The targets of these drugs were predicted using Swiss Target Prediction, while IMN-related genes with association scores under 5 were gathered from the GeneCards and DisGeNET databases. The common targets of the disease and the components were determined using VENNY 2.1. Using Cytoscape 3.8.0, a drug-disease network diagram was created. Molecular docking was carried out with Pymol, AutoDock Tools, and AutoDock Vina. Results: With 1260 IMN-related illness genes gathered from GeneCards and DisGeNET databases, we were able to identify 5 potentially active chemicals and their 169 target proteins in Huangkui. Based on degree value, the top 6 targets for Huangkui treatment of IMN were chosen, including AKT, MAPK3, PPARG, MMP9, ESR1, and KDR. Conclusion: This work theoretically explains the mechanism of action of Huangkui Capsule in treating IMN and offers a foundation for using Huangkui Capsule in treating IMN in clinical settings. The findings require additional experimental validation.
32
Gani, Maria Apriliani, Ahmad Dzulfikri Nurhan, Aniek Setiya Budiatin, Siswandono Siswodihardjo, and Junaidi Khotib. "Predicting the molecular mechanism of glucosamine in accelerating bone defect repair by stimulating osteogenic proteins." Journal of Basic and Clinical Physiology and Pharmacology 32, no. 4 (2021): 373–77. http://dx.doi.org/10.1515/jbcpp-2020-0403.
Full textAbstract:
Abstract Objectives Bone defect is serious condition that is usually caused by traffic accident. Chitosan is a polymer developed as a scaffold to treat bone defect. However, the mechanism by which chitosan can accelerate bone growth in defect area is still unclear. This study aims to identify proteins which are crucial to the osteogenic properties of chitosan monomer using an in silico study. Methods Molecular docking was carried out on chitosan monomer, which are d-glucosamine and glucosamine 6-phosphate units against bone morphogenetic protein 2 (BMP-2), fibronectin, fibroblast growth factor (Fgf), and phosphate transporter (PiT) using AutoDock Vina. Ligand preparation was carried out using Chem3D version 15.0.0.106, while protein preparation was performed using AutoDockTools version 1.5.6. Results The results showed that glucosamine 6-phosphate had the best binding affinity with fibronectin and PiT, which was −5.7 kcal mol−1 on both proteins, while d-glucosamine had the best binding affinity with PiT (−5.2 kcal mol−1). Conclusions This study suggests that the osteogenic properties of chitosan may be due to the presence of bonds between glucosamine units and fibronectin and/or PiT. However, in vitro studies need to be done to prove this.
33
M, Dr Karthikeyan, and Praveen B M. "In Silico Molecular Docking of Aminoglycosides as Topoisomerase 1 Inhibitors: A Computational approach." South Asian Journal of Experimental Biology 14, no. 5 (2025): 232–41. https://doi.org/10.38150/sajeb.14(5).p232-241.
Full textAbstract:
Cancer remains a leading cause of mortality worldwide, necessitating the discovery of novel therapeutic agents to combat this disease. The present study focuses on identifying drug-like molecules with anticancer properties through an in silico approach, targeting the human topoisomerase I-DNA complex (PDB ID: 1A35), a critical enzyme in DNA replication and repair. The primary objectives were to evaluate the binding affinity and drug-likeness of selected ligands, including antibiotics (gentamicin and amikacin) and chemotherapeutic agents (irinotecan and topotecan), using computational tools. The protein structure was prepared and energy-minimized, while ligands were sketched using ChemDraw Ultra 8.0, converted to 3D forms, and energy-minimized using Chem3D Pro 8.0. Molecular docking was performed using AutoDock Vina PyRx, and interactions were visualized with Biovia Discovery Studio 2024 Client. The results revealed binding energies of -6.2 and -6.7 kcal/mol for amikacin and gentamicin, respectively, and -8.4 and -7.6 kcal/mol for irinotecan and topotecan, respectively, indicating strong interactions with the target protein. These findings underscore the potential of these compounds as promising candidates for anticancer drug development, particularly due to their favorable binding affinities and adherence to Lipinski’s Rule of Five. This study highlights the significance of computational approaches in accelerating drug discovery and provides a foundation for further experimental validation of these molecules as potential anticancer agents.
34
Widyaningrum, D., R. A. Oktafika, and D. Cecilia. "Microalgae pigments as a promising immunomodulating food ingredient: In silico study." IOP Conference Series: Earth and Environmental Science 998, no. 1 (2022): 012056. http://dx.doi.org/10.1088/1755-1315/998/1/012056.
Full textAbstract:
Abstract Microalgae pigments attract the commercial market as functional food ingredients because of their potential as an antioxidant and anti-inflammatory agents. Through in vitro and in vivo studies, microalgae pigments showed a potential therapeutic effect to reduce the expression of pro-inflammatory cytokines by inhibiting inflammation signaling. Our study explored the potency of microalgae pigments as an immunomodulator by modeling the direct interaction between pigments and pro-inflammatory proteins by molecular docking. The docking study was carried out using AutoDock Vina. At the same time, the binding visualization was obtained by using Discovery Studio Visualizer. The result showed all investigated microalgae pigments (i.e., phycocyanobilin, astaxanthin, β-carotene, 9-cis- (β-carotene, and violaxanthin) docked to pro-inflammatory proteins (i.e., IL-6, TNF-α, and NIK), respectively in various binding energy. The binding between pigment compounds and the target protein is mostly attributed to the Van der Waals interaction. Notably, the pigments docked in crucial residues in proinflammatory proteins, suggesting the effect of the protein interaction on its receptor and cytokines activity. The results showed a therapeutic potency of microalgae pigment to support immune system modulation that could prevent and attenuate chronic inflammation.
35
Saleem, Muhammad, Sumaira Hareem, Ajmal Khan, et al. "Dual inhibitors of urease and carbonic anhydrase-II from Iris species." Pure and Applied Chemistry 91, no. 10 (2019): 1695–707. http://dx.doi.org/10.1515/pac-2019-0407.
Full textAbstract:
Abstract Twenty seven (1–27) known natural organic compounds were isolated for first time from two species of Iris, i.e. loczyi and Iris unguicularis. The structures of these compounds were deduced from the spectral data of NMR, IR, and mass spectrogram. These were evaluated against urease and carbonic anhydrase inhibition studies. For carbonic anhydrase-II inhibition studies, these compounds were evaluated by biochemical mechanism based in vitro bio-assay. Some compounds showed significant inhibition against CA-II enzyme. Compartively, compound (12) showed IC50 value of 17.60 ± 0.08 μM against urease enzyme, while compound (3) was found to be most active against carbonic anhydrase-II, having an IC50 value of 66.27 ± 0.89 μM. Izalpinin (3), 5,7-dihydroxy-2′,6-dimethoxyisoflavone (9), 4′,5,7-trihydroxy-6-methoxyflavanone (16), 4′,5,7-trihydroxy-3′,8-dimethoxyflavanone (20), 8-methoxyeriodictyol (21), and mangiferin (26) were found to be dual inhibitors of both the enyzmes. The most active compounds were docked using Autodock Vina and i-GEMDOCK softwares. The docking and in-vitro results are in agreement which showed secondary interactions with the enzymes. The compounds can serve as therapeutic agents to treat urease and carbonic anhydrase associated disorders.
36
Wu, Jiadai, Helen Power, Monica Miranda-Saksena, et al. "Identifying HSV-1 Inhibitors from Natural Compounds via Virtual Screening Targeting Surface Glycoprotein D." Pharmaceuticals 15, no. 3 (2022): 361. http://dx.doi.org/10.3390/ph15030361.
Full textAbstract:
Herpes simplex virus (HSV) infections are a worldwide health problem in need of new effective treatments. Of particular interest is the identification of antiviral agents that act via different mechanisms compared to current drugs, as these could interact synergistically with first-line antiherpetic agents to accelerate the resolution of HSV-1-associated lesions. For this study, we applied a structure-based molecular docking approach targeting the nectin-1 and herpesvirus entry mediator (HVEM) binding interfaces of the viral glycoprotein D (gD). More than 527,000 natural compounds were virtually screened using Autodock Vina and then filtered for favorable ADMET profiles. Eight top hits were evaluated experimentally in African green monkey kidney cell line (VERO) cells, which yielded two compounds with potential antiherpetic activity. One active compound (1-(1-benzofuran-2-yl)-2-[(5Z)-2H,6H,7H,8H-[1,3] dioxolo[4,5-g]isoquinoline-5-ylidene]ethenone) showed weak but significant antiviral activity. Although less potent than antiherpetic agents, such as acyclovir, it acted at the viral inactivation stage in a dose-dependent manner, suggesting a novel mode of action. These results highlight the feasibility of in silico approaches for identifying new antiviral compounds, which may be further optimized by medicinal chemistry approaches.
37
Devgan, Manish. "STRUCTURE PREDICTION AND IN SILICO DESIGNING OF DRUGS AGAINST KALLIKREIN PROTEIN 12." International Journal of Current Pharmaceutical Research 9, no. 2 (2017): 64. http://dx.doi.org/10.22159/ijcpr.2017v9i2.17387.
Full textAbstract:
Objective: Human Kallikrein protein 12 (hK12) might serve as a novel diagnostic and prognostic biomarker, as well as a potential therapeutic target, in gastric cancer.Methods: In this work, a theoretical model of hK12 receptor protein was generated using the concepts of homology modeling and loop modeling. The resulting model was validated with Ramachandran plot analysis. The ligands generated with the help of Drug bank were docked against hK12 receptor protein using AutoDock Vina in PyRx 0.8. The structure of ligand DB04786 (Suramin), with least binding energy, was varied by using ACD/ChemSketch 8.0 and the docking was done for the resulting 16 new ligands.Results: The results indicated that the ligand10 bears the minimum binding energy (-12.3 Kcal/mol) with the target protein and thus the prospects of binding are high. The results also clearly demonstrated that the in silico molecular docking studies of selected ligands, i.e., suramin, ligands 5, 6, 10 and 16 with hK12 protein exhibited favourable binding interactions and warranted.Conclusion: Further studies needed for the development of potent inhibitors for the overexpression of hK12 protein making the management of gastric cancer more efficient.
38
Alsanie, Walaa F., Abdulhakeem S. Alamri, Hussain Alyami, et al. "Increasing the Efficacy of Seproxetine as an Antidepressant Using Charge–Transfer Complexes." Molecules 27, no. 10 (2022): 3290. http://dx.doi.org/10.3390/molecules27103290.
Full textAbstract:
The charge transfer interactions between the seproxetine (SRX) donor and π-electron acceptors [picric acid (PA), dinitrobenzene (DNB), p-nitrobenzoic acid (p-NBA), 2,6-dichloroquinone-4-chloroimide (DCQ), 2,6-dibromoquinone-4-chloroimide (DBQ), and 7,7′,8,8′-tetracyanoquinodi methane (TCNQ)] were studied in a liquid medium, and the solid form was isolated and characterized. The spectrophotometric analysis confirmed that the charge–transfer interactions between the electrons of the donor and acceptors were 1:1 (SRX: π-acceptor). To study the comparative interactions between SRX and the other π-electron acceptors, molecular docking calculations were performed between SRX and the charge transfer (CT) complexes against three receptors (serotonin, dopamine, and TrkB kinase receptor). According to molecular docking, the CT complex [(SRX)(TCNQ)] binds with all three receptors more efficiently than SRX alone, and [(SRX)(TCNQ)]-dopamine (CTcD) has the highest binding energy value. The results of AutoDock Vina revealed that the molecular dynamics simulation of the 100 ns run revealed that both the SRX-dopamine and CTcD complexes had a stable conformation; however, the CTcD complex was more stable. The optimized structure of the CT complexes was obtained using density functional theory (B-3LYP/6-311G++) and was compared.
39
Zhou, Boqian, Yongguang Zhang, Wanyun Jiang, and Haiyang Zhang. "Virtual Screening of FDA-Approved Drugs for Enhanced Binding with Mitochondrial Aldehyde Dehydrogenase." Molecules 27, no. 24 (2022): 8773. http://dx.doi.org/10.3390/molecules27248773.
Full textAbstract:
Mitochondrial aldehyde dehydrogenase (ALDH2) is a potential target for the treatment of substance use disorders such as alcohol addiction. Here, we adopted computational methods of molecular dynamics (MD) simulation, docking, and molecular mechanics Poisson–Boltzmann surface area (MM-PBSA) analysis to perform a virtual screening of FDA-approved drugs, hitting potent inhibitors against ALDH2. Using MD-derived conformations as receptors, butenafine (net charge q = +1 e) and olaparib (q = 0) were selected as promising compounds with a low toxicity and a binding strength equal to or stronger than previously reported potent inhibitors of daidzin and CVT-10216. A few negatively charged compounds were also hit from the docking with the Autodock Vina software, while the MM-PBSA analysis yielded positive binding energies (unfavorable binding) for these compounds, mainly owing to electrostatic repulsion in association with a negatively charged receptor (q = −6 e for ALDH2 plus the cofactor NAD+). This revealed a deficiency of the Vina scoring in dealing with strong charge–charge interactions between binding partners, due to its built-in protocol of not using atomic charges for electrostatic interactions. These observations indicated a requirement of further verification using MD and/or MM-PBSA after docking prediction. The identification of key residues for the binding implied that the receptor residues at the bottom and entrance of the substrate-binding hydrophobic tunnel were able to offer additional interactions with different inhibitors such as π-π, π-alkyl, van der Waals contacts, and polar interactions, and that the rational use of these interactions is beneficial to the design of potent inhibitors against ALDH2.
40
Hassanzadeh, Elham, Shahram Khademvatan, Behzad Jafari, Abbas Jafari, and Elham Yousefi. "In vitro and in silico scolicidal effect of sanguinarine on the hydatid cyst protoscoleces." PLOS ONE 18, no. 10 (2023): e0290947. http://dx.doi.org/10.1371/journal.pone.0290947.
Full textAbstract:
We aimed to investigate the scolicidal effects of sanguinarine on hydatid cyst protoscoleces (PSCs) in vitro and in silico. Different targets were docked into the active sites of sanguinarine. Molecular docking processes and visualization of interactions were performed using AutoDock Vina and Discovery Studio Visualizer. Binding energy was calculated and compared (kcal/mol). PSCs were aspirated from the hydatid cysts and washed. The sediments of PSCs were then exposed to various concentrations (50, 25, 12, 6, 3, and 1 μg/mL) of sanguinarine. The viability test was finally evaluated by the Trypan blue solution 4%. Levels of malondialdehyde (MDA), superoxide dismutase (SOD), glutathione (GSH), glutathione peroxidase (GPX), and catalase were analyzed to assess the level of oxidative stress-treated PSCs. Caspase-3 activity rate was determined to evaluate cell apoptosis in treated PSCs. Among the receptors, acetylcholinesterase was identified as the excellent target, with Vina score of -11.8. Sanguinarine showed high scolicidal effects after 12, 24, and 48 h. Also, in the first hour of exposure to the drug, caspase-3 activity and MDA level significantly increased, but the levels of GSH and GPx had a significant reduction after 12, 24, and 48 h (P < 0.05). The findings of this study revealed that sanguinarine have potent scolicidal effects in vitro and in silico and could be considered an opportunity for the introduction of a novel and safe therapeutic agent for the treatment of cystic echinococcosis. However, supplementary studies will be desired to prove the current findings by examining sanguinarine in a clinical setting.
41
Ahadini, Putri Aliya, Adhyatma Ismu Reihan, Muhamad Bagus Wira Utama, Siti Khaerunnisa, and Fadilah Fadilah. "In-Silico Study: Potential Inhibitor of Cyclin-Dependent Kinase 6 (CDK6) from Natural Plant Compounds for Melanoma Treatment." JUXTA: Jurnal Ilmiah Mahasiswa Kedokteran Universitas Airlangga 13, no. 2 (2022): 93–99. http://dx.doi.org/10.20473/juxta.v13i22022.93-99.
Full textAbstract:
Highlights:1. Melanoma is the most aggressive and dangerous type of skin cancer. 2. Cyclin-dependent kinase 6 (CDK6) had a role in melanoma progression.3. Chlorogenic acid, guattegaumerine, luteolin, and acronycine were potential natural compounds in plants as CDK6 inhibitors. AbstractIntroduction: Melanoma is the most aggressive and dangerous type of skin cancer. It usually occurs in the skin because melanocytes originate from the neural crest cells that migrate. A previous study stated misregulation of cyclin-dependent kinase 6 (CDK6) had a role in melanoma progression. This study aimed to identify the potential natural compound targeting and modulating the CDK6.Methods: This was an investigative study using in-silico docking analysis to search for compatible ligands and potential inhibitors to CDK6 protein. This study screened 46 natural compounds based on the drug-likeliness based on Lipinski’s rules of five and used PyRx (AutoDock Vina) software for the initial screening. 10 compounds with the highest binding energy underwent docking simulation using Molecular Operating Environment (MOE) software.Results: Chlorogenic acid, guattegaumerine, luteolin, and acronycine were potential natural compounds in plants as CDK6 inhibitors.Conclusion: This study found that chlorogenic acid was the most potential to be an inhibitor of CDK6 compared to other compounds screened.
42
Layla, Athiyah, Sri Widyarti, and Sutiman Bambang Sumitro. "IN SILICO STUDY OF HYDROGEN PEROXIDE (H2O2) BINDING EFFECT TO EXTRACELLULAR SIGNAL-REGULATED KINASES (ERK)." Berkala Penelitian Hayati 30, no. 2 (2024): 1–9. http://dx.doi.org/10.23869/bphjbr.30.2.20245.
Full textAbstract:
H2O2 can provide a physiological response by activating Mitogen activated protein kinase (MAPK) signaling components, it can phosphorylate and activate several regulatory proteins, which are closely related to gene expression, and growth promotion. H2O2 has neuroprotective abilities and potential to be a complementary therapy. It can be implemented in Parkinson Disease (PD) therapy, by activating Extracellular signal-regulated kinases (ERK/1/2/5) play central role in the control of endothel cell proliferation and activate apoptosis signal-regulating kinase 1 (ASK1), key modulators of the apoptosis cell or death balance. The main pathology of PD is amyloid fibrils composed of αSyn (α-Synuclein), can cause disruption of the blood-brain barrier (BBB.) Aggregate of αSyn caused mitochondrial dysfunction, dysregulation and apoptosis in barrier-type brain endothelial cells (BECs), it leads BBB leakage, increase BBB permeability and disrupt L-DOPA transport. Therefore, treatments that prevent vascular degeneration may be new targets for the of PD. This research used in silico method. The 3D structures of ligand and protein target was retrieved from PubChem and protein data bank (PDB). Ligand was converted using the Open Babel and molecular docking program used AutoDock Vina, as a plug-in in PyRx. Results were analysed using PyMOL and Discovery Studio. Molecular dynamics simulation used YASARA. From this study, H2O2 lowering RMSD and RMSF value of ERK 1/2/5 and ASK1. It is known that H2O2 can stabilize ERK 1/2/5 and ASK1.
43
Ezebuo, Fortunatus Chidolue, Colin B. Lukong, Ikemefuna C. Uzochukwu, and Irene N. Okafor. "In silico investigations revealed four potential colon cancer drugs from phytochemicals in Zingiber officinale." International Journal of Phytomedicine 8, no. 3 (2016): 435. http://dx.doi.org/10.5138/09750185.1886.
Full textAbstract:
<p align="left">Cancer is a difficult disease to treat, and few effective drugs are available. Hence, it is of great importance to develop effective anti-cancer therapeutic agents with well-defined pharmacokinetic properties.<strong> </strong>Although, ginger (<em>Zingiber officinale</em>) has a number of proven pharmacological activities, its effect on colon cancer has not received much attention. This study therefore investigated the potential colon cancer drug of compounds found in ginger. Dihydropyrimidine dehydrogenase was modeled using comparative homology modeling and virtual screening was performed locally on a Linux platform using AutoDock Vina<sup>®</sup>. The results showed that human dihydropyrimidine dehydrogenase is a homolog of pig dihydropyrimidine dehydrogenase. The leads of potential colon cancer drugs were beta-sitosterol, 6-Shogoal, Alloaromadedrene, and Zingiberol. They had similar binding site with levamisole for tumor necrosis factor ligand superfamily member 6 with His 148 and Tyr 192 common at their binding site whereas they had different binding sites from 5-fluorouracil for dihydropyrimidine dehydrogenase. The leads had better bioactivities compared with reference drugs (5-flourouracil and Levamisole) approved clinically for the treatment of colon cancer. <em>In vitro</em>, <em>ex vivo</em> and/or <em>in vivo</em> validations of the leads against colon cancer are recommended. <strong></strong></p>
44
Iheagwam, Franklyn Nonso, Olubanke Olujoke Ogunlana, and Shalom Nwodo Chinedu. "Model Optimization and In Silico Analysis of Potential Dipeptidyl Peptidase IV Antagonists from GC-MS Identified Compounds in Nauclea latifolia Leaf Extracts." International Journal of Molecular Sciences 20, no. 23 (2019): 5913. http://dx.doi.org/10.3390/ijms20235913.
Full textAbstract:
Dipeptidyl peptidase IV (DPP-IV) is a pharmacotherapeutic target in type 2 diabetes. Inhibitors of this enzyme constitute a new class of drugs used in the treatment and management of type 2 diabetes. In this study, phytocompounds in Nauclea latifolia (NL) leaf extracts, identified using gas chromatography–mass spectroscopy (GC-MS), were tested for potential antagonists of DPP-IV via in silico techniques. Phytocompounds present in N. latifolia aqueous (NLA) and ethanol (NLE) leaf extracts were identified using GC–MS. DPP-IV model optimization and molecular docking of the identified compounds/standard inhibitors in the binding pocket was simulated. Drug-likeness, pharmacokinetic and pharmacodynamic properties of promising docked leads were also predicted. Results showed the presence of 50 phytocompounds in NL extracts of which only 2-O-p-methylphenyl-1-thio-β-d-glucoside, 3-tosylsedoheptulose, 4-benzyloxy-6-hydroxymethyl-tetrahydropyran-2,3,5-triol and vitamin E exhibited comparable or better binding iGEMDOCK and AutoDock Vina scores than the clinically prescribed standards. These four compounds exhibited promising drug-likeness as well as absorption, distribution, metabolism, excretion and toxicity (ADMET) properties suggesting their candidature as novel leads for developing DPP-IV inhibitors.
45
Omoboyowa, Damilola Alex, Toheeb Adewale Balogun, Oluwaseun Motunrayo Omomule, and Oluwatosin A. Saibu. "Identification of Terpenoids From Abrus precatorius Against Parkinson’s Disease Proteins Using In Silico Approach." Bioinformatics and Biology Insights 15 (January 2021): 117793222110507. http://dx.doi.org/10.1177/11779322211050757.
Full textAbstract:
Parkinson’s disease (PD) is the second major neuro-degenrative disorder that causes morbidity and mortality among older populations. Terpenoids were reported as potential neuro-protective agents. Therefore, this study seeks to unlock the inhibitory potential of terpenoids from Abrus precatorius seeds against proteins involve in PD pathogenesis. In this study, in silico molecular docking of 5 terpenoids derived from high-performance liquid chromatography (HPLC) analysis of A. precatorius seeds against α-synuclein, catechol-o-methyltransferase, and monoamine oxidase B which are markers of PD was performed using Autodock vina. The absorption, distribution, metabolism, excretion, and toxicity (ADME/Tox) of the hits were done using Swiss ADME predictor and molecular dynamic (MD) simulation of the hit-protein complex was performed using Desmond Schrodinger software. Five out of 6 compounds satisfied the ADME/Tox parameters and showed varying degrees of binding affinities with selected proteins. Drimenin-α-synuclein complex showed the lowest binding energy of −9.1 kcal/mol followed by interaction with key amino acid residues necessary for α-synuclein inhibition. The selection of this complex was justified by its stability in MD simulation conducted for 10 ns and exhibited stable interaction in terms of root mean square deviation (RMSD) and root mean square deviation error fluctuation (RMSF) values.
46
Luo, Xiaowei, Lipeng Zhou, Shukai Wang, et al. "The Therapeutic Effect and the Potential Mechanism of Flavonoids and Phenolics of Moringa oleifera Lam. Leaves against Hyperuricemia Mice." Molecules 27, no. 23 (2022): 8237. http://dx.doi.org/10.3390/molecules27238237.
Full textAbstract:
The aim of this study is to evaluate the anti-hyperuricemia effect and clarify the possible mechanisms of flavonoids and phenolics of MOL (MOL-FP) in mice. Hyperuricemia mice were generated via intraperitoneal (i.p.) administration of potassium oxonate (PO) and oral gavage (p.o.) of hypoxanthine (HX). Serum uric acid (UA), weight, serum XO activity, hepatic XO activity, urea nitrogen (BUN), creatinine (CRE), serum AST level, serum ALT level, mRNA expression of renal urate-anion transporter 1 (URAT1), glucose transporter 9 (GLUT9), organic anion transporters 1 (OAT1), organic anion transporters 3 (OAT3), and ATP-binding cassette transporter G2 (ABCG2) were determined. The molecular docking was conducted using AutoDock Vina 1.2.0 to screen potential XO inhibitors in MOL-FP. Serum metabolomics was established to collect the metabolic profiles of mice and explore the metabolic changes that occurred after MOL-FP treatment. MOL-FP could notably reduce the serum UA level of hyperuricemia mice by inhibiting XO activity and regulating renal urate transporters. Molecular docking studies indicated that 5-p-coumaroylquinic acid, 3-p-coumaroylquinic acid, and catechin could be potential XO inhibitors. Besides, MOL-FP prevented the pathological process of hyperuricemia by regulating biomarkers associated with purine metabolism, amino acid metabolism, and lipid metabolism.
47
Côrtes Filho, Aldo Barbosa, Danyo Maia Lima, Pâmala Évelin Pires Cedro, et al. "In silico screening of brazilian semiarid compounds to identify potential drugs with glucocorticoid receptor interaction." Research, Society and Development 9, no. 9 (2020): e734997865. http://dx.doi.org/10.33448/rsd-v9i9.7865.
Full textAbstract:
The glucocorticoid receptor regulates the anti-inflammatory response, and prevents transcription of anti-inflammatory substances such as nuclear factor kB and lipocortin-1, IL-2, IL-6, TNF and prostaglandins. Thus, a search for new molecules with potential interaction with the glucocorticoid receptor is an interesting strategy for the treatment of inflammatory diseases. Virtual screening has proven to be a viable tool for discovering new products at lower cost and practicality. Thus, the aim of this study is to identify and evaluate brazilian semiarid compounds with anti-inflammatory potential with glucocorticoid receptor action through molecular coupling. Protein selection was performed by searching the 3D structure database, Protein Data Bank. A total of 382 semi-arid molecules available in the ZINC database of State University of Feira de Santana (UEFS) were used. Molecular docking was performed using Autodock Vina and as interaction clouds analyzed by the Discovery Studio Visualizer program. Mometasone furoate shows a binding energy of -12.7 Kcal.mol-1. A ZINC 69481862 molecule fits Lipinski and Veber rules, however, the best interaction was the ZINC 69482012 molecule, evidenced by the binding energy -11.2 Kcal.mol-1. Analyses of intermolecular interactions have shown that Van der Waals interactions and electrostatic bonds are crucial for the binding of the molecule at the receptor's active site. It is necessary to test in vitro to verify the viability and toxicity of the potential drug.
48
Nguyen, Xuan Ha, Thi Thu Le Vu, Tien Lam Do, Minh Quan Pham, and Thanh Dat Vu. "Evaluation of anti-inflammatory compounds isolated from Millettia dielsiana Harms ex Diels by molecular docking method." Vietnam Journal of Science and Technology 60, no. 5 (2022): 785–93. http://dx.doi.org/10.15625/2525-2518/16469.
Full textAbstract:
In this study, we focused on screening and simulating the interaction between anti-inflammatory proteins and 50 compounds isolated from Millettia dielsiana Harms ex Diels. 39 out of 50 compounds that violated no of Lipinski’s rule of five were sorted out as favorable for drug development and selected for studies further. Then, a molecular docking study of compounds into the binding sites of COX-1 and COX-2 allowed shedding light on the binding mode of these potential COX inhibitors performed using Autodock Vina software. Our results showed that 6 compounds, including millesianin E (D32), barbigerone (D18), millesianin D (D31), (+)-epicatechin (D11), durallone (D17), and ichthynone (D19) exhibited good binding energy with the cyclooxygenase-2 (COX-2) enzyme meanwhile all of the selected compounds exhibited poor binding energy to the cyclooxygenase-1 (COX-1) enzyme. The binding energies of these compounds range from -8.6 kcal/mol to -9.0 kcal/mol better than the standard compounds Valdecoxib and Lumiracoxib. In addition, an analysis of the COX-2 enzyme and selected compounds binding was also presented. The important binding modes shown at the active site of the COX-2 enzyme through hydrogen bonds compared with standard compounds showed this as potential candidates against this enzyme. Therefore, these results might give a positive signal in finding anti-inflammatory drugs from Millettia dielsiana.
49
Tambe, Siddhi S., Rohini R. Pujari, Vishnu P. Chaudhari, and Sandesh Lodha. "MOLECULAR DOCKING AND ADMET BASED MINING OF NATURAL COMPOUNDS FROM PTEROCARPUS MARSUPIUM AGAINST PRIME TARGETS OF DIABETES MELLITUS." INDIAN DRUGS 61, no. 04 (2024): 16–29. http://dx.doi.org/10.53879/id.61.04.14318.
Full textAbstract:
In the Ayurvedic system of medicine, Pterocarpus marsupium Linn bark extract is used for the treatment of diabetes. It has a rich profile of chemical constituents. However, phytochemicals with antidiabetic activity are not reported yet. To comprehend more about this plant’s antidiabetic mechanism of action, 26 reported phytochemicals, namely, pterostilbene, marsupsin/ carpusin, 7-O-α-L-rhamnopyranosyloxy4′-methoxy-5-hydroxy isoflavone, (-)-epicatechin, pterosupin, liquiritigenin, vijayoside, pteroside, propterol-b, beta-eudesmol, pseudobaptigenin, isoliquiritigenin, garbanzol, 5-de-oxykaempferol, catechol, gallic acid, 3,4-dihydroxybenzoic acid, naringetol, 4-hydroxybenzaldehyde, trans-stilbene, 3,7,4’-trihydroxyflavone, 7,4’-dihydroxyflavone, (2S)-7-hydroxyflavanone, oleanolic acid, lupeol and marsupol/ebanol, were subjected to molecular docking studies using six targets of diabetes, namely, C and N-terminal subunits of human maltase-glucoamylase, glucagon like peptide-1, N-terminal sucraseisomaltase, human peroxisome proliferator-activated receptor –α and ϒ. The docking studies were carried out using PyRx and AutoDock Vina 1.1.2 software. Compounds with optimum binding affinity were subjected to evaluate drug likeliness and toxicity using SwissADME and admetSAR web tools. Vijayoside was found to have maximum affinity (-8.5 Kcal mol-1) with N-terminal subunit of human maltaseglucoamylase. The binding energies of O-α-L-rhamnopyranosyloxy-4'-methoxy-5-hydroxy isoflavone was found to be maximum with C-terminal (-10.0 Kcal mol-1). Danugliprion, a standard, was found to have maximum binding affinity (-11.4 Kcal mol-1) with glucagon-like peptide-1. Pteroside was found to bind favorably (-7.5 Kcal mol-1) with N-terminal sucrase-isomaltase.7-O-α-L-rhamnopyranosyloxy4′-methoxy-5-hydroxy isoflavone has exhibited stable interactions with other receptors (-10.2 and -8.2 Kcal mol-1 for human peroxisome proliferator-activated receptor–α and ϒ). These three phytochemicals also exhibited druggability properties. Further in vitro and in vivo studies may fully validate the results.
50
Đào, Thị Hồng Loan, Thị Mai Hương Nguyễn, Trung Kiên Trần, Thu Nhung Trần, Doãn Phú Nguyễn та Thụy Việt Phương Nguyễn. "Nghiên cứu tìm kiếm các hợp chất tự nhiên tiềm năng ức chế protein E1 của Human papilloma virus 18". Y HOC TP. HO CHI MINH 27, № 3 (2024): 1–8. http://dx.doi.org/10.32895/hcjm.p.2024.03.01.
Full textAbstract:
Mục tiêu: Tìm kiếm các hợp chất tự nhiên (HCTN) có tiềm năng ức chế protein E1 của Human papillomavirus 18 (HPV 18) hướng điều trị ung thư cổ tử cung thông qua các phương pháp như gắn kết phân tử, mô phỏng động lực học phân tử (MDs) và tính toán năng lượng gắn kết. Đối tượng và phương pháp nghiên cứu: Xác định ái lực gắn kết của các HCTN với E1 thông qua gắn kết phân tử sử dụng AutoDock Vina, khảo sát độ ổn định của phức hợp E1 với phối tử bằng MDs và tính toán năng lượng gắn kết tương đối (MM/PBSA, MM/GBSA) và tuyệt đối (LIE) bằng GROMACS. Kết quả: 5 HCTN có điểm số gắn kết tốt trên E1 và tương tác với acid amin quan trọng (Lys237 và Thr238) gồm E157 (neobudofficid: -13,88 kcal.mol-1), E176 (epimedin C: -11,44 kcal.mol-1), E186 (hispidulin-7-O-rutinosid: -15,32 kcal.mol-1), E221 (limonin: -19,88 kcal.mol-1) và E254 (cucurbitacin E: -8,75 kcal.mol-1). Cả 5 HCTN ổn định trong 100 ns của MDs. Năng lượng gắn kết của 5 HCTN bằng MM/PBSA và MM/GBSA đều tương tự kết quả gắn kết phân tử, trong đó E186 và E221 có năng lượng tốt nhất. Phương pháp LIE cho thấy chỉ có E186 gắn kết tốt với E1. Kết luận: Nghiên cứu cho thấy tiềm năng phát triển các HCTN trên tác dụng ức chế E1 của HPV 18. Từ khóa: ung thư cổ tử cung, HPV 18, E1, gắn kết phân tử, mô phỏng động lực học phân tử, năng lượng liên kết