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1
Albu, Paul Constantin, Szidonia-Katalin Tanczos, Andreea Ferencz (Dinu), et al. "pH and Design on n–Alkyl Alcohol Bulk Liquid Membranes for Improving Phenol Derivative Transport and Separation." Membranes 12, no. 4 (2022): 365. http://dx.doi.org/10.3390/membranes12040365.
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Regardless of the type of liquid membrane (LM) (Bulk Liquid Membranes (BLM), Supported Liquid Membranes (SLM) or Emulsion Liquid Membranes (ELM)), transport and separation of chemical species are conditioned by the operational (OP) and constructive design parameters (DP) of the permeation module. In the present study, the pH of the aqueous source phase (SP) and receiving phase (RP) of the proposed membrane system were selected as operational parameters. The mode of contacting the phases was chosen as the convective transport generator. The experiments used BLM-type membranes with spheres in free rotation as film contact elements of the aqueous phases with the membrane. The target chemical species were selected in the range of phenol derivatives (PD), 4–nitrophenol (NP), 2,4–dichlorophenol (DCP) and 2,4–dinitrophenol (DNP), all being substances of technical-economic and environmental interest. Due to their acid character, they allow the evaluation of the influence of pH as a determining operational parameter of transport and separation through a membrane consisting of n–octanol or n–decanol (n–AlcM). The comparative study performed for the transport of 4–nitrophenol (NP) showed that the module based on spheres (Ms) was more performant than the one with phase dispersion under the form of droplets (Md). The sphere material influenced the transport of 4–nitrophenol (NP). The transport module with glass spheres (Gl) was superior to the one using copper spheres (Cu), but especially with the one with steel spheres (St). In all the studied cases, the sphere-based module (Ms) had superior transport results compared to the module with droplets (Md). The extraction efficiency (EE) and the transport of 2,4–dichlorophenol (DCP) and 2,4–dinitrophenol (DNP), studied in the module with glass spheres, showed that the two phenolic derivatives could be separated by adjusting the pH of the source phase. At the acidic pH of the source phase (pH = 2), the two derivatives were extracted with good results (EE > 90%), while for pH values ranging from 4 to 6, they could be separated, with DCP having doubled separation efficiency compared to DNP. At a pH of 8 in the source phase, the extraction efficiency halved for both phenolic compounds.
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Knight, C. G. "A quenched fluorescent substrate for thimet peptidase containing a new fluorescent amino acid, DL-2-amino-3-(7-methoxy-4-coumaryl)propionic acid." Biochemical Journal 274, no. 1 (1991): 45–48. http://dx.doi.org/10.1042/bj2740045.
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DL-2-Amino-3-(7-methoxy-4-coumaryl)propionic acid, a new fluorescent amino acid (abbreviated to Amp), has been synthesized to provide an alternative to tryptophan in quenched fluorescent peptide substrates for peptidases. The model compound Ac-DL-Amp-NH2 was intensely fluorescent with an excitation maximum at 328 nm and an emission maximum at 392 nm. Fmoc (fluoren-9-ylmethoxycarbonyl)-DL-Amp was made to allow the solid-phase synthesis of Amp-containing peptides by the Fmoc-polyamide method. The peptide derivative Dnp (2,4-dinitrophenyl)-Pro-Leu-Gly-Pro-DL-Amp-D-Lys was cleaved by thimet peptidase at the Leu-Gly bond, with a 20-fold enhancement of fluorescence. The value of kcat./Km for thimet peptidase was 6.7 x 10(5) M-1.s-1, compared with the value of 2.4 x 10(5) M-1.s-1 for the tryptophan-containing analogue, Dnp-Pro-Leu-Gly-Pro-Trp-D-Lys.
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Li, Dongmi, Panpan Lv, Xiao-Wen Han, Zhilei Jia, Min Zheng, and Hai-Tao Feng. "A Highly Efficient Fluorescent Sensor Based on AIEgen for Detection of Nitrophenolic Explosives." Molecules 28, no. 1 (2022): 181. http://dx.doi.org/10.3390/molecules28010181.
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The detection of nitrophenolic explosives is important in counterterrorism and environmental protection, but it is still a challenge to identify the nitroaromatic compounds among those with a similar structure. Herein, a simple tetraphenylethene (TPE) derivative with aggregation-induced emission (AIE) characteristics was synthesized and used as a fluorescent sensor for the detection of nitrophenolic explosives (2, 4, 6-trinitrophenol, TNP and 2, 4-dinitrophenol, DNP) in water solution and in a solid state with a high selectivity. Meanwhile, it was found that only hydroxyl containing nitrophenolic explosives caused obvious fluorescence quenching. The sensing mechanism was investigated by using fluorescence titration and 1H NMR spectra. This simple AIE-active probe can potentially be applied to the construction of portable detection devices for explosives.
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MOHD., ALI, and SHARMA NlRMAL. "Characterisation of Chemical Constituents of Gliricidia meculata Leaves." Journal of Indian Chemical Society Vol. 74, Aug 1997 (1997): 658–59. https://doi.org/10.5281/zenodo.5895292.
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Faculty of Pharmacy, Jarnia Hamdard (Hamdard University), Hamdard Nagar, New Delhi-110 062 <em>Manuscript received 16 June 1994, revised 15 February 1996, accepted 24 June 1996</em> Characterisation of Chemical Constituents of Gliricidia meculata Leaves.
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Dust, Julian M., and Richard A. Manderville. "Carbon versus oxygen nucleophilic selectivity in the reaction of the aryloxide ions, 2,6- and 3,5-di-tert-butylphenoxide, with the 2-[(nitro)\dn6 xaryl]-4,6-dinitrobenzotriazole 1-oxide series of super-electrophiles. Stereoelectronic factors on C-7 Meisenheimer complex formation versus C-1' SNAr displacement." Canadian Journal of Chemistry 76, no. 6 (1998): 662–71. http://dx.doi.org/10.1139/v98-028.
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The 2-[(nitro)xaryl]-4,6-dinitrobenzotriazole 1-oxides (1, Pi-DNBT (x = 3); 2, DNP-DNBT (x = 2); 3, NP-DNBT (x = 1)) are electron-deficient nitro-substituted heteroaromatic substrates that possess two sites for nucleophilic attachment: C-7 and C-1'. Generally, attack at the super-electrophilic C-7 site yields spectroscopically observable anionic sigma -bonded adducts, whereas attack at C-1' leads to displacement products in an overall process of nucleophilic aromatic substitution (SNAr). To gain an understanding of the factors affecting C-1' versus C-7 attack by potentially ambident aryloxide (C- and O-)nucleophiles, we have monitored the reactions of 1-3 with 2,6-di-tert-butylphenoxide (2,6-ArO-) and 3,5-di-tert-butylphenoxide (3,5-ArO-) using 400 MHz 1H NMR spectroscopy (deuterated dimethyl sulfoxide solvent at ambient temperature). The results indicate that 2,6-ArO- acts only as a C-nucleophile with O-attack precluded, presumably by the sterically demanding tert-butyl groups flanking the O-nucleophilic centre. Although 2,6-ArO- reacts preferentially at C-7 of 1-3, the biphenyl derivative that arises from C-1' attack is also observed with 1, the first time that C-nucleophilic attack has been seen at this electrophilic site. In contrast, 3,5-ArO- acts only as an O-nucleophile, also as a consequence of the steric hindrance to the C-4 position; this aryloxide reacts entirely at C-1' of Pi-DNBT but also exclusively at C-7 of 3. However, with DNP-DNBT, 2, both the C-7 O-adduct and C-1' displacement products are noted; attack at C-1' is dominant. The selectivity (C-7 versus C-1') found in these reactions is discussed with emphasis given to stereoelectronic factors that may stabilize the putative C-1' O-adducts.Key words: aryloxides, super-electrophiles, Meisenheimer complexes, 2-[(nitro)xaryl]-4,6-dinitrobenzotriazole 1-oxides.
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Panwar, Ritik, Vikash Jakhmola, Supriyo Saha, Sunil Jawla, and Ravinesh Mishra. "Molecular Docking, MD Simulation, and Antiproliferative Activity of Pyridazine Derivatives." International Journal of Drug Delivery Technology 15, no. 02 (2025): 01–09. https://doi.org/10.25258/ijddt.15.2.48.
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Pyridazine derivative showed much diversified activity. Previously 77 pyridazine derivatives were synthesized and evaluated the antihypertensive property. Pyridazine derivatives also showed antitumor and antiproliferative behavior. By kept this idea in mind we repurposed those pyridazine derivatives towards antiproliferation using in silico, and in vitro methods. Molecular docking analysis of pyridazine derivatives against DNA (PDB id: 6BNA) were performed and top4 molecules (R45, R60, R67, R70) were identified based on their docking scores. Then 100 ns MD simulation and MMPBSA analysis of these molecules were performed using GROMACS software. MD simulation data showed good RMSD, radius of gyration, SASA, and hydrogen bond analysis. Pyridazine derivative (R67) showed good simulation behavior with very minimum fluctuation within the receptor. Free binding energy of R67 was (-) 42.683 kJ/mol. R67 showed marked GI50 value against MCF7 cell line using sulphorhodamine assay. Among the pyridazine derivatives Among the synthesized molecules 6-([1,1'-biphenyl]-4-yl)-2-(4-([1,1'-biphenyl]-4-yl)-5-thioxo-4,5-dihydro-1H-1,2,4- triazol-3-yl)-4,5-dihydropyridazin-3(2H)-one (R67) showed best antiproliferative activity with in silico insights.
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Nicolás, Álvaro, Julia G. Quero, Marta Barroso, Zoila Gándara, and Lourdes Gude. "DNA Interactions and Biological Activity of 2,9-Disubstituted 1,10-Phenanthroline Thiosemicarbazone-Based Ligands and a 4-Phenylthiazole Derivative." Biology 13, no. 1 (2024): 60. http://dx.doi.org/10.3390/biology13010060.
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Four 1,10-phenanthroline derivatives (1–4) were synthesized as potential telomeric DNA binders, three substituted in their chains with thiosemicarbazones (TSCs) and one 4-phenylthiazole derivative. The compounds were characterized using NMR, HRMS, FTIR-spectroscopy and combustion elemental analysis. Quadruplex and dsDNA interactions were preliminarily studied, especially for neutral derivative 1, using FRET-based DNA melting assays, equilibrium dialysis (both competitive and non-competitive), circular dichroism and viscosity titrations. The TSC derivatives bind and stabilize the telomeric Tel22 quadruplex more efficiently than dsDNA, with an estimated 24-fold selectivity determined through equilibrium dialysis for compound 1. In addition, cytotoxic activity against various tumor cells (PC-3, DU145, HeLa, MCF-7 and HT29) and two normal cell lines (HFF-1 and RWPE-1) was evaluated. Except for the 4-phenylthiazole derivative, which was inactive, the compounds showed moderate cytotoxic properties, with the salts displaying lower IC50 values (30–80 μM), compared to the neutral TSC, except in PC-3 cells (IC50 (1) = 18 μM). However, the neutral derivative was the only compound that exhibited a modest selectivity in the case of prostate cells (tumor PC-3 versus healthy RWPE-1). Cell cycle analysis and Annexin V/PI assays revealed that the compounds can produce cell death by apoptosis, an effect that has proven to be similar to that demonstrated by other known 1,10-phenanthroline G4 ligands endowed with antitumor properties, such as PhenDC3 and PhenQE8.
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Aleo, Danilo, Venera Cardile, Rosa Chillemi, Giuseppe Granata, and Sebastiano Sciuto. "Chemoenzymatic Synthesis and Some Biological Properties of O-phosphoryl Derivatives of (E)-resveratrol." Natural Product Communications 3, no. 10 (2008): 1934578X0800301. http://dx.doi.org/10.1177/1934578x0800301023.
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3- O-, 3,5-di- O- and 4′- O-phosphoryl derivatives of ( E)-resveratrol have been obtained following a chemoenzymatic strategy. Variedly acylated resveratrol derivatives have been obtained first by exploiting regioselective properties of Pseudomonas cepacea or Candida antarctica lipases in organic solvents. Each acyl-resveratrol was then phosphorylated by the phosphoramidite chemistry protocol and in sequence freed of protective groups, affording the desired O-phosphoryl derivative. Following UV-absorption spectroscopic investigation on the interaction of the newly synthesized compounds with DNA, 4′- O-phosphorylresveratrol exhibited the best binding affinity. As a result of cytotoxicity tests, 3- O-phosphorylresveratrol was more active than resveratrol against DU 145 prostate cancer cells.
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Stolarczyk, Marcin, Agnieszka Matera-Witkiewicz, Aleksandra Wolska, et al. "Synthesis, Crystal Structure, and Biological Evaluation of Novel 5-Hydroxymethylpyrimidines." Materials 14, no. 22 (2021): 6916. http://dx.doi.org/10.3390/ma14226916.
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Pyrimidine displays a wide array of bioactivities, and thence, it is still considered a potent unit of new drug research. Its derivative, 5-hydroxymethylpyrimidine, can be found as a scaffold of nontypical nitrogen bases in DNA and as a core of some natural bioactive compounds. In this study, we obtained a series of 5-hydroxymethylpyrimidines that vary in the 4-position by the reduction of proper esters. All compounds were characterized by spectroscopic analysis, and single-crystal X-ray diffraction was performed for some of them. Biological investigations estimated cytotoxic properties against normal (RPTEC) and cancer (HeLa, HepaRG, Caco-2, AGS, A172) cell lines. It was found that the derivatives with an aliphatic amino group at the 4-position are generally less toxic to normal cells than those with a benzylsulfanyl group. Moreover, compounds with bulky constituents exhibit better anticancer properties, though at a moderate level. The specific compounds were chosen due to their most promising IC50 concentration for in silico study. Furthermore, antimicrobial activity tests were performed against six strains of bacteria and one fungus. They demonstrated that only derivatives with at least three carbon chain amino groups at the 4-position have weak antibacterial properties, and only the derivative with 4-benzylsulfanyl constituent exhibits any antifungal action.
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Orchel, Arkadiusz, Ewa Chodurek, Marzena Jaworska-Kik, et al. "Anticancer Activity of the Acetylenic Derivative of Betulin Phosphate Involves Induction of Necrotic-Like Death in Breast Cancer Cells In Vitro." Molecules 26, no. 3 (2021): 615. http://dx.doi.org/10.3390/molecules26030615.
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Betulin (BT) is a natural pentacyclic lupane-type triterpene exhibiting anticancer activity. Betulin derivatives bearing propynoyloxy and phosphate groups were prepared in an effort to improve the availability and efficacy of the drug. In this study, a comparative assessment of the in vitro anticancer activity of betulin and its four derivatives was carried out using two human breast cancer cell lines: SK-BR-3 and MCF-7. In both studied cell lines, 30-diethoxyphosphoryl-28-propynoylbetulin (compound 4) turned out to be the most powerful inhibitor of growth and inducer of cellular death. Detailed examination of that derivative pertained to the mechanisms underlying its anticancer action. Treatment with compound 4 decreased DNA synthesis and up-regulated p21WAF1/Cip1 mRNA and protein levels in both cell lines. On the other hand, that derivative caused a significant increase in cell death, as evidenced by increased lactate dehydrogenase (LDH) release and ethidium homodimer uptake. Shortly after the compound addition, an increased generation of reactive oxygen species and loss of mitochondrial membrane potential were detected. The activation of caspase-3 and fragmentation of genomic DNA suggested an apoptotic type of cell death. However, analysis of cellular morphology did not reveal any nuclear features typical of apoptosis. Despite necrosis-like morphology, dead cells exhibited activation of the cascade of caspases. These observations have led to the conclusion that compound 4 pushed cells to undergo a form of necrotic-like regulated cell demise.
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Ayudha, Vety Sri Harlinda, and Mokhamat Ariefin. "Synthesis and Characterization of Pyrazine Derived Compounds as Potential Materials for Hole Transporting Layer (HTL)." Jurnal Kimia Sains dan Aplikasi 23, no. 6 (2020): 228–33. http://dx.doi.org/10.14710/jksa.23.6.228-233.
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Three simple compounds that have the potential as a hole transporting layer (HTL) based on pyrazine derivatives conjugated with electron donor groups in the form of triphenylamine have been successfully synthesized and characterized. The synthesis began with a substitution reaction at high temperatures between 4-bromoaniline and 4-iodoanisole to produce 4-bromo-N,N-bis(methoxyphenyl)-aniline, followed by substitution of bromo atoms with tributylstanum at low temperatures and inert atmosphere (N2) producing 4-methoxy-N-(4-(tributylstanyl)phenyl)aniline. The conjugation reaction was carried out through a Stille coupling reaction between 1,2-bis (4-bromophenyl)ethane-1,2-dione with 4-methoxy-N-(4-(tributylstanyl)phenyl) aniline at high temperatures with the aid of a Pd(PPh3)4 catalyst in an inert atmosphere (N2). The reaction was continued with the imination reaction with 3 compounds, i.e., 1,2-diaminobenzene, 3,3-diaminobenzidine and 2,3-diaminopiridin to produce three HTL compounds that were namely 4’,4”-(quinoxaline-2,3-diyl)bis (N,N-bis(4(methoxyphenyl)-[1,1’-biphenyl]-4-amine) (DNB), 4’,4’’’,4’’’’’,4’’’’’’’-([6,6’-biquinoxaline]-2,2’,3,3’-tetrayl) tetrakis(N,N-bis(4-methoxyphenyl)- [1,1’-biphenyl] -4-amine) (bDNB), and 4’,4’’’-(pyrido[2,3-b]pyrazine-2,3-diyl)bis(N,N-bis (4-methoxyphenyl)-[1,1’-biphenyl]-4-amine) (DNP). The optical and electrochemical properties of DNB, bDNB, and DNP were analyzed by UV-Vis and Differential Pulse Voltammetry (DPV). The optical and electrochemical properties show the energy levels of the HOMO and LUMO of the three compounds. Hence their potential can be estimated as HTL compounds. The three compounds show λmax of 348 nm, 356 nm, and 350 nm for DNB, bDNB, and DNP. Based on DPV results, the HOMO values for DNB, bDNB, and DNP are -5.03 eV, -5.02 eV, and -4.98 eV and LUMO values of -2.46 eV, -2.76 eV and -2.87 eV, respectively. The three compounds' thermal properties were analyzed using TGA, with the results showing that the three compounds had good thermal resistance with a decomposition point above 400°C. Based on optical, electrochemical, and thermal analysis, DNB and bDNB have almost the same properties. Thus, it is expected that the three compounds have the potential as HTL material, with DNB and bDNB better than DNP.
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B. Bakare, S. "Synthesis and biological evaluation of some hybrid 2-quinolinone derivatives containing cinnamic acid as anti-breast cancer drugs." Bulletin of the Chemical Society of Ethiopia 35, no. 3 (2022): 551–64. http://dx.doi.org/10.4314/bcse.v35i3.7.
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ABSTRACT. A new series of hybrid 2-quinolinone derivatives were synthesized by using 7-hydroxy-4-methyl-1-amino-quinolin-2-one (2) and cinnamic acid. Hybrid halogenated 2-quinolinone derivatives (3-(7-hydroxy-4-methyl-3,6,8-tribromo-2-oxo-2H-quinolin-1-ylamino)-3-phenyl acrylic acid (4) and 3-(7-acetoxy-4-methyl-3,6,8-tribromo-2-oxo-1H-quinolin-1-ylamino)-3-phenyl acrylic acid (7)) were prepared via the halogenation of 3-(7-hydroxy-4-methyl-2-oxo-2H-quinolin-1-ylamino)-3-phenyl acrylic acid (3) with bromine to give compound 4 with acetic anhydride led to the formation of hydride halogenated 2-quinolinone derivative (7). All the synthesized hybrid 2-quinolinone and hybrid halogenated 2-quinolinone derivatives were tested for their cytotoxicity against MCF-7 cell line. DNA flow cytometric analysis of compounds 3 showed cell cycle arrest at G2/M phase with concomitant increase of cells in apoptotic phase. Dual annexin-V/propidium iodide staining assay of compound 3 revealed that, the selected molecule increases the apoptosis of MCF-7 cells more than control.
 
 KEY WORDS: Quinolinone, Hybrid, Cinnamic acid, Apoptosis, MCF-7 cells
 
 Bull. Chem. Soc. Ethiop. 2021, 35(3), 551-564.
 DOI: https://dx.doi.org/10.4314/bcse.v35i3.7
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Szostek, Tomasz, Daniel Szulczyk, Jolanta Szymańska-Majchrzak, et al. "Design and Synthesis of Menthol and Thymol Derived Ciprofloxacin: Influence of Structural Modifications on the Antibacterial Activity and Anticancer Properties." International Journal of Molecular Sciences 23, no. 12 (2022): 6600. http://dx.doi.org/10.3390/ijms23126600.
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Sixteen new Ciprofloxacin derivatives were designed and successfully synthesized. In an in silico experiment, lipophilicity was established for obtained compounds. All compounds were screened for antimicrobial activity using standard and clinical strains. As for Gram-positive hospital microorganisms, all tested derivatives were active. Measured MICs were in the range 1–16 µg/mL, confirming high antimicrobial potency. Derivative 12 demonstrated activity against all standard Gram-positive Staphylococci, within the range of 0.8–1.6 µg/mL and was confirmed as the leading structure with MICs 1 µg/mL for S. pasteuri KR 4358 and S. aureus T 5591 (clinical strains). All compounds were screened for their in vitro cytotoxic properties via the MTT method. Three of the examined compounds (3, 11 and 16) showed good activity against cancer cells, and in parallel were found not to be cytotoxic toward normal cells. Doxorubicin SI ranged 0.14–1.11 while the mentioned three ranged 1.9–3.4. Selected Ciprofloxacin derivatives were docked into the crystal structure of topoisomerase II (DNA gyrase) in complex with DNA (PDB ID: 5BTC). In summary, leading structures were established (3, 11, 12 and 16). We have observed poor results in preformed studies for disubstituted derivatives, suggesting that 3-oxo-4-carboxylic acid core is the active DNA-gyrase binding site, and when structural changes were made in this fragment, there was an observed decrease in antibacterial potency.
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Rucins, Martins, Pavels Dimitrijevs, Klavs Pajuste, et al. "Contribution of Molecular Structure to Self-Assembling and Biological Properties of Bifunctional Lipid-Like 4-(N-Alkylpyridinium)-1,4-Dihydropyridines." Pharmaceutics 11, no. 3 (2019): 115. http://dx.doi.org/10.3390/pharmaceutics11030115.
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The design of nanoparticle delivery materials possessing biological activities is an attractive strategy for the development of various therapies. In this study, 11 cationic amphiphilic 4-(N-alkylpyridinium)-1,4-dihydropyridine (1,4-DHP) derivatives differing in alkyl chain length and propargyl moiety/ties number and position were selected for the study of their self-assembling properties, evaluation of their cytotoxicity in vitro and toxicity on microorganisms, and the characterisation of their interaction with phospholipids. These lipid-like 1,4-DHPs have been earlier proposed as promising nanocarriers for DNA delivery. We have revealed that the mean diameter of freshly prepared nanoparticles varied from 58 to 513 nm, depending upon the 4-(N-alkylpyridinium)-1,4-DHP structure. Additionally, we have confirmed that only nanoparticles formed by 4-(N-dodecylpyridinium)-1,4-DHP derivatives 3 and 6, and by 4-(N-hexadecylpyridinium)-1,4-DHP derivatives 10 and 11 were stable after two weeks of storage. The nanoparticles of these compounds were found to be homogenous in size distribution, ranging from 124 to 221 nm. The polydispersity index (PDI) values of 1,4-DHPs samples 3, 6, 10, and 11 were in the range of 0.10 to 0.37. We also demonstrated that the nanoparticles formed by 4-(N-dodecylpyridinium)-1,4-DHP derivatives 3, 6, and 9, and 4-(N-hexadecylpyridinium)-1,4-DHP derivatives 10 and 11 had zeta-potentials from +26.07 mV (compound 6) to +62.80 mV (compound 11), indicating a strongly positive surface charge and confirming the relative electrostatic stability of these nanoparticle solutions. Transmission electron microscopy (TEM) images of nanoaggregates formed by 1,4-DHPs 3 and 11 confirmed liposome-like structures with diameters around 70 to 170 nm. The critical aggregation concentration (CAC) value interval for 4-(N-alkylpyridinium)-1,4-DHP was from 7.6 µM (compound 11) to 43.3 µM (compound 6). The tested 4-(N-alkylpyridinium)-1,4-DHP derivatives were able to quench the fluorescence of the binary 1,6-diphenyl-1,3,5-hexatriene (DPH)—1,2-dipalmitoyl-sn-glycero-3-phosphocholine (DPPC) system, demonstrating hydrophobic interactions of 1,4-DHPs with phospholipids. Thus, 4-(N-dodecylpyridinium)-1,4-DHP derivative 3 quenched the fluorescence of the DPH–DPPC system more efficiently than the other 4-(N-alkylpyridinium)-1,4-DHP derivatives. Likewise the compound 3, also 4-(N-dodecylpyridinium)-1,4-DHP derivative 9 interacted with the phospholipids. Moreover, we have established that increasing the length of the alkyl chain at the quaternised nitrogen of the 4-(N-alkylpyridinium)-1,4-DHP molecule or the introduction of propargyl moieties in the 1,4-DHP molecule significantly influences the cytotoxicity on HT-1080 (human fibrosarcoma) and MH-22A (mouse hepatocarcinoma) cell lines, as well as the estimated basal cytotoxicity. Additionally, it was demonstrated that the toxicity of the 4-(N-alkylpyridinium)-1,4-DHP derivatives on the Gram-positive and Gram-negative bacteria species and eukaryotic microorganism depended on the presence of the alkyl chain length at the N-alkyl pyridinium moiety, as well as the number of propargyl groups. These lipid-like compounds may be proposed for the further development of drug formulations to be used in cancer treatment.
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Akrami, Hamidreza, Bibi Fatemeh Mirjalili, Omidreza Firuzi, et al. "Cytotoxic Activity and DNA Binding Property of New Aminopyrimidine Derivatives." Letters in Drug Design & Discovery 17, no. 5 (2020): 640–54. http://dx.doi.org/10.2174/1570180816666190712102119.
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Background: Chromene and anilinopyrimidine heterocyclics are attractive anticancer compounds that have inspired many researchers to design novel derivatives bearing improved anticancer activity. Methods: A series of pyrimidine-fused benzo[f]chromene derivatives 6a-x were synthesized as anticancer hybrids of 1H-benzo[f]chromenes and anilinopyrimidines. The inhibitory activity of the synthesized compounds 6a-x against cell viability of human chronic myelogenous leukemia (K562), human acute lymphoblastic leukemia (MOLT-4) and human breast adenocarcinoma (MCF-7) cell lines was evaluated using MTT assay. The interaction of the most promising compound with calf-thymus DNA was also studied using spectrometric titrations and Circular Dichroism (CD) spectroscopy. Results: Most compounds showed promising activity against tested cell lines. Among them, 2,4- dimethoxyanilino derivative 6g exhibited the best profile of activity against tested cell lines (IC50s = 1.6-6.1 μM) with no toxicity against NIH3T3 normal cell (IC50 >200 μM). The spectrometric studies exhibited that compound 6g binds to DNA strongly and may change DNA conformation significantly, presumably via a groove binding mechanism. Conclusion: The results of this study suggest that the prototype compound 6g can be considered as a novel lead compound for the design and discovery of novel anticancer agents.
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Hikisz, Pawel, Piotr Wawrzyniak, Angelika A. Adamus-Grabicka, Damian Jacenik, and Elzbieta Budzisz. "Evaluation of In Vitro Biological Activity of Flavanone/Chromanone Derivatives: Molecular Analysis of Anticancer Mechanisms in Colorectal Cancer." International Journal of Molecular Sciences 25, no. 23 (2024): 12985. https://doi.org/10.3390/ijms252312985.
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The primary objective of this study was to evaluate the anticancer activity of six flavanone/chromanone derivatives: 3-benzylideneflavanones/3-benzylidenechroman-4-ones and their 3-spiro-1-pirazolines analogs. We employed five colon cancer cell lines with varying degrees of metastasis and genetic profiles as our research model. Our investigation focused primarily on assessing the pro-oxidant properties of the tested derivatives and their impact on overall antiproliferative activity. To comprehensively evaluate the cytotoxic properties of these compounds, we analyzed their genotoxic, pro-apoptotic, and autophagy-inducing effects. Our findings indicate that three of the six analyzed derivatives exhibited promising antiproliferative activity against cancer cells, with IC50 values ranging from 10 to 30 μM. Strong pro-oxidant properties were identified as a key mechanism underlying their cytotoxic activity. The generation of oxidative stress, which varied depending on the specific flavanone/chromanone derivative, resulted from increased intracellular reactive oxygen species (ROS) levels and decreased glutathione (GSH) concentrations. Furthermore, oxidative stress likely contributed to the induction of apoptosis/autophagy in cancer cells and the emergence of significant DNA damage.
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Kopru, Semiha, Fatma Ozturk Küp, Nazmiye Sabanci, et al. "DNA Cleavage Properties, Antimicrobial and Cytotoxic Activity and 4D-QSAR Analysis of Some Pyrazole Derivatives." Letters in Drug Design & Discovery 16, no. 8 (2019): 904–18. http://dx.doi.org/10.2174/1570180815666180926104319.
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Background:An extensive study of 19 pyrazole derivatives were carried out based on the evaluation of DNA cleavage properties, antimicrobial and cytotoxic activities and 4D-QSAR analysis including pharmacophore modelling and bioactivity prediction by the Electron Conformational-Genetic Algorithm (EC-GA) method.Methods:The pyrazole derivatives were tested for their antimicrobial activity against certain human pathogenic organisms using the agar diffusion procedure. Binding of compounds with DNA was studied by gel electrophoresis using plasmid pBR322 DNA. The compounds were investigated for their properties as cytotoxic agents by brine shrimp lethality bioassay. To identify the pharmacophoric elements and find out the most important molecular properties which govern cytotoxic activity, multiple conformations of the compounds were used.Results:The urea derivatives of pyrazole had higher antibacterial activities against Gram-negative bacteria than against Gram-positive bacteria. Many of the compounds were found to cleave plasmid pBR322 DNA from the supercoiled form to the nicked circular. The cytotoxicity values of the compounds ranged from 13.87 to 84.1 µg/mL. The generated QSAR model was evaluated through the use of the Leave-One-Out Cross Validation (LOO-CV) method. A statistically significant and considerably predictive QSAR model was obtained with 4- descriptors resulting in R2 training =0.8223, R2 test =0.9346, q2=0.6201, q2 ext1=0.8672, q2 ext2= 0.8662 and q2 ext3=0.9511.Discussion:The generated model demonstrates that geometrical parameters are more correlated with cytotoxic activity. The resulting EC-GA model would provide benefits to design novel bioactive pyrazole derivatives which are more potent and have less side effects.Conclusion:It is believed that the generated QSAR model gives insight into developing new more potent pyrazole derivative drugs.
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Izadi, Farhad, Adrian Szczyrba, Magdalena Datta, et al. "Electron-Induced Decomposition of 5-Bromo-4-thiouracil and 5-Bromo-4-thio-2′-deoxyuridine: The Effect of the Deoxyribose Moiety on Dissociative Electron Attachment." International Journal of Molecular Sciences 24, no. 10 (2023): 8706. http://dx.doi.org/10.3390/ijms24108706.
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When modified uridine derivatives are incorporated into DNA, radical species may form that cause DNA damage. This category of molecules has been proposed as radiosensitizers and is currently being researched. Here, we study electron attachment to 5-bromo-4-thiouracil (BrSU), a uracil derivative, and 5-bromo-4-thio-2′-deoxyuridine (BrSdU), with an attached deoxyribose moiety via the N-glycosidic (N1-C) bond. Quadrupole mass spectrometry was used to detect the anionic products of dissociative electron attachment (DEA), and the experimental results were supported by quantum chemical calculations performed at the M062X/aug-cc-pVTZ level of theory. Experimentally, we found that BrSU predominantly captures low-energy electrons with kinetic energies near 0 eV, though the abundance of bromine anions was rather low compared to a similar experiment with bromouracil. We suggest that, for this reaction channel, proton-transfer reactions in the transient negative ions limit the release of bromine anions.
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Rakas, Anja, Leentje Persoons, Dirk Daelemans, Dajana Kučić Grgić, and Tatjana Gazivoda Kraljević. "A Sustainable Synthesis of Novel 2-(3,4-Disubstituted phenyl)benzoxazole Derivatives and Their Antiproliferative and Antibacterial Evaluation." Molecules 30, no. 8 (2025): 1767. https://doi.org/10.3390/molecules30081767.
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This study describes the synthesis of O-alkylated benzaldehydes 1–8, Schiff bases 9–28, and benzoxazole derivatives 29–48 using microwave, ultrasound, and mechanochemical reactions, as well as reactions in deep eutectic solvents in excellent yields, and their antiproliferative and antibacterial activities. The in vitro evaluation of antiproliferative activity for the newly synthesised benzoxazole derivatives 29–48 against a diverse panel of human cancer cell lines, such as LN-229, Capan-1, HCT-116, NCI-H460, DND-41, HL-60, K-562, and Z-138 demonstrated that the majority of these benzoxazole derivatives displayed promising anticancer activity, particularly against non-small cell lung cancer (NSCLC) cells (NCI-H460). Notably, several derivatives showed enhanced activity compared to the included reference drug, etoposide. Considering the influence of substituents at position 5 of the benzoxazole ring and positions 3 and 4 of the phenyl ring on the antiproliferative activity, it is evident that derivatives 41–48 bearing a methoxy group at position 3 generally exhibit higher activity compared to compounds 29–40, which lack substitution at position 3. Furthermore, derivatives substituted at position 4 with a morpholine substituent, as well as those with an N,N-diethyl group, exhibited higher activity compared to other evaluated benzoxazole derivatives. The in vitro antibacterial evaluation against Gram-positive and Gram-negative bacteria revealed that benzoxazole derivative 47 exhibited notable activity, against the Gram-negative bacterium Pseudomonas aeruginosa (MIC = 0.25 μg/mL) and the Gram-positive bacterium Enterococcus faecalis (MIC = 0.5 μg/mL). The results point out that this class of benzoxazoles can be efficiently synthesized using eco-friendly methods and represent promising candidates for further design and optimization aimed at developing potent antiproliferative agents.
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Panagopoulos, Anastasios, Konstantina Alipranti, Kyriaki Mylona, et al. "Exploration of the DNA Photocleavage Activity of O-Halo-phenyl Carbamoyl Amidoximes: Studies of the UVA-Induced Effects on a Major Crop Pest, the Whitefly Bemisia tabaci." DNA 3, no. 2 (2023): 85–100. http://dx.doi.org/10.3390/dna3020006.
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The DNA photocleavage effect of halogenated O-carbamoyl derivatives of 4-MeO-benzamidoxime under UVB and UVA irradiation was studied in order to identify the nature, position, and number of halogens on the carbamoyl moiety that ensure photoactivity. F, Cl, and Br-phenyl carbamate esters (PCME) exhibited activity with the p-Cl-phenyl derivative to show excellent photocleavage against pBR322 plasmid DNA. m-Cl-PCME has diminished activity, whereas the presence of two halogen atoms reduced DNA photocleavage. The substitution on the benzamidoxime scaffold was irrelevant to the activity. The mechanism of action indicated function in the absence of oxygen, probably via radicals derived from the N-O bond homolysis of the carbamates and in air via hydroxyl radicals and partially singlet oxygen. The UVA-vis area of absorption of the nitro-benzamidoxime p-Cl-PCMEs allowed for the investigation of their potential efficacy as photopesticides under UVA irradiation against the whitefly Bemisia tabaci, a major pest of numerous crops. The m-nitro derivative exhibited a moderate specificity against the adult population. Nymphs were not affected. The compound was inactive in the dark. This result may allow for the development of lead compounds for the control of agricultural insect pests that can cause significant economic damage in crop production.
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Chandrasekar, Kamatchi, Bhawani Kumar, Arunkumar Saravanan, et al. "Evalution and Molecular Docking of Benzimidazole and its Derivatives as a Potent Antibacterial Agent." Biomedical and Pharmacology Journal 12, no. 04 (2019): 1835–47. http://dx.doi.org/10.13005/bpj/1814.
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The study was performed to identify a potent antibacterial benzimidazole derivative using in vitro and in silico techniques. Benzimidazole and its derivatives were synthesized by reflux process. The derivatives were screened for antibiotic susceptibility test (AST) and minimum inhibitory concentration (MIC) against Gram-negative and Gram-positive clinical isolates and compared with the positive control Norfloxacin. Insilico molecular docking was performed to screen the binding potential of the derivatives with target enzymes topoisomerase II /DNA gyraseof Escherichia coli (E.coli) and Staphylococcus aureus (S.aureus) along with the control Norfloxacin.Totally fifty-four isolates were screened for antimicrobial supectibility test (AST) and minimum inhibitory concentration (MIC) and 35 clinical isolates of Gram-negative showed 86% resistance to Norfloxacin and 19 isolates of Gram-positive showed 90% resistance to Norfloxacin. However, these isolates were found to be sensitive to 1-(4-((1H–benzimidazol-1-yl) methylamino) phenyl) ethanone (3) (C2), and 2-methyl-1H-benzimidazole (C4) compounds, with MIC ranges from 6.25- 12.5 µg/ml. Molecular docking analysis revealed that the compound C2 exhibited better binding affinity towards topoisomerase II / DNA gyrase of E.coli and S.aureus when compared with C4 and control Norfloxacin. The antibacterial activity of these may due to the inactivation of these enzymes which is supported by the MIC results.The obtained in vitro and in silico results suggested that C2 showed better antimicrobial activity.
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N., Raman, Baskaran T., Jeyaveeramadhavi S., and Dhaveethu Raja J. "DNA cleavage efficiency of transition metal(II) Schiff base cmnplexes of 4-aminoantipyrine derivative : Synthesis, characterization and antimicrobial study." Journal of Indian Chemical Society Vol. 84, Jul 2007 (2007): 652–57. https://doi.org/10.5281/zenodo.5823912.
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Department of Chemistry, VHNSN College, Virudhunagar-626 001, Tamilnadu, India <em>E-mail</em> : drn_raman@yahoo.co.in <em>Manuscript received 18 May 2007, accepted 21 May 2007</em> A new bidentate Schiff base ligand derived from 4-aminoantipyrine and <em>o</em>-acetoacetotoluidide and its Cu<sup>ll</sup>, Co<sup>II</sup>, Ni<sup>II</sup> and Zn<sup>II</sup> metal complexes have been synthesized and characterized by microanalytical data, IR, UV-Vis, <sup>1</sup>H NMR and mass spectra. The conductance measurements indicate that all the complexes are electrolytes. The IR spectra indicate the coordination of azomethine nitrogen atom of the Schiff base and cyclic carbonyl group of the pyrazolone ring. The UV-Vis spectral data demonstrate that the complexes have square-planar geometry. The FAB mass spectra confirm ·the composition of the complexes of the type ML<sub>2</sub> where M = Cu<sup>II</sup> , Co<sup>II</sup> , Ni<sup>II</sup> and Zn<sup>II</sup> • Their magnetic susceptibility values provide evidence for the monomeric nature. The gel electrophoresis experiment has been carried out on the interaction of the complexes with CT-DNA. The nuclease activity of the above metal complexes shows that only the copper complex cleaves DNA in the presence of oxidant. Antimicrobial activities of the compounds are tested <em>vitro</em> against four bacteria and three fungi by the disc diffusion method. The MIC value against the growth of microorganisms is much larger for metal chelates than the ligand.
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Drzewiecka-Antonik, Aleksandra, Marta Struga, Agnieszka Głogowska, et al. "Synthesis, Structural Characterization and Biological Activity Evaluation of Novel Cu(II) Complexes with 3-(trifluoromethyl)phenylthiourea Derivatives." International Journal of Molecular Sciences 23, no. 24 (2022): 15694. http://dx.doi.org/10.3390/ijms232415694.
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Copper complexes with 1,3-disubstituted thiourea derivatives, all containing 3-(trifluoromethyl)phenyl tail and 1-alkyl/halogen-phenyl substituent, were synthesized. The experimental spectroscopic studies and theoretical calculation revealed that two ligands coordinate to Cu(II) in a bidentate fashion via thiocarbonyl S and deprotonated N atoms of thiourea moiety. Such monomers are characteristic of alkylphenylthiourea complexes, whereas the formation of a sandwich-type dimer is observed for halogeno derivatives. For the first time, the structural identifications of CuN2S2-based complexes using experimental and theoretical X-ray absorption near edge structure are demonstrated. The dimeric halogeno derivatives showed higher antimicrobial activity in comparison with alkylphenylthiourea complexes. The Cu(II) complex of 1-(4-chloro-3-nitrophenyl)-3-[3-(trifluoromethyl)phenyl]thiourea was active against 19 strains of methicillin-resistant Staphylococci (MIC = 2 µg/mL). This derivative acted as a dual inhibitor of DNA gyrase and topoisomerase IV isolated from Staphylococcus aureus. Additionally, complexes of halogenphenylthiourea strongly inhibited the growth of mycobacteria isolated from tuberculosis patients, even fourfold stronger than the reference isoniazid. The complexes exerted weak to moderate antitumor activity (towards SW480, SW620, and PC3) being non-toxic towards normal HaCaT cells.
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Mandal, Tripti, Arka Dey, Sudipta Pathak, et al. "Structures, photoresponse properties and DNA binding abilities of 4-(4-pyridinyl)-2-pyridone salts." RSC Advances 9, no. 17 (2019): 9663–77. http://dx.doi.org/10.1039/c9ra00666d.
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The optical band gap energies in several 2-pyridone derivatives have been measured using solid state UV to explore their semiconductor behavior. The electric current measurements for the four compounds exhibit enhanced photoconduction properties under irradiation of light.
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Uwabagira, Nadine, Balladka K. Sarojini, and Ashwini Prabhu. "Synthesis, In Vitro Anticancer, Anti-Inflammatory and DNA Binding Activity of Thiazolidinedione Derivatives." Anti-Cancer Agents in Medicinal Chemistry 20, no. 14 (2020): 1704–13. http://dx.doi.org/10.2174/1871520620666200424102615.
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Background: Cancer is the second leading cause of mortality worldwide. Despite several advances made in the treatment strategies, the cure for cancer remains still a challenge. Currently used treatment modalities pose several side effects and remain ineffective in the later stages. Thiazolidinediones (TZDs) have been shown to possess anti-cancer activity in several in vitro models. Objectives: The objective of this study was to assess the effect of novel synthesized thiazolidinedione derivatives on three selected cancer cell lines viz., human breast adenocarcinoma cell line (MCF-7), lung adenocarcinoma (A549) and colorectal carcinoma (HT29). This study also aimed to evaluate the anti-inflammatory and DNA binding activity of the synthesized derivatives. Methods: The synthesized thiazolidinedione derivatives were screened for their in vitro anti-cancer activity on the human breast adenocarcinoma cell line (MCF-7), lung adenocarcinoma (A549) and colorectal carcinoma (HT29) using the Methyl Thaizolyl Tetrazolium (MTT) Assay. They were also evaluated for in vitro antiinflammatory activity using albumin denaturation method, DNA binding activity and hemocompatibility. Results: Compounds 5a, 5b, 5d, 6c and 6d showed IC50 of 30.19, 41.56, 65.97, 60.16 and 50.41μM respectively on breast adenocarcinoma (MCF-7), IC50 of 49.75, 51.42, 65.43, 61.94 and 56.80μM on lung adenocarcinoma (A549) and 38.11, 45.58, 71.24, 53.15 and 51.25μM on colorectal carcinoma (HT29). In the hemolysis assay, compounds 5a and 5b were found to be nontoxic and nonhemolytic to human erythrocytes. Five compounds possessed significant anticancer and anti-inflammatory activity. Three of them are Mannich bases, whereas the remaining two are aryl acyl derivatives. Conclusion: The in vitro results (anticancer and anti-inflammatory) showed that the 4-chloro anilinomethyl substitution at third position and thiophenoethenyl at the fifth position of thiozolidinedione (5a) emerged as the most effective derivative on all the tested cancer cell lines. A higher DNA binding affinity of the test compounds was also found.
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Liang, Dinghua, Xing Wu, Brian B. Hasinoff, David E. Herbert, and Geoffrey K. Tranmer. "Evaluation of Nitrobenzyl Derivatives of Camptothecin as Anti-Cancer Agents and Potential Hypoxia Targeting Prodrugs." Molecules 23, no. 8 (2018): 2041. http://dx.doi.org/10.3390/molecules23082041.
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As part of our initial efforts into developing a tumor-targeting therapy, C-10 substituted derivatives of a camptothecin analog (SN-38) have been synthesized (2-, 3- and 4-nitrobenzyl) for use as potential hypoxia-activated prodrugs and evaluated for their cytotoxicity, topoisomerase I inhibition and electrochemical (reductive) properties. All three derivatives were found to possess reduced toxicity towards human leukemia K562 cells compared to SN-38, validating a condition for prodrug action. Using an MTS assay, IC50’s were found to be 3.0, 25.9, 12.2 and 58.0 nM for SN-38, 2-nitro-, 3-nitro- and 4-nitrobenzyl-C10-substituted-SN-38, respectively, representing an 8-, 4- and 19-fold decrease in cytotoxicity. Using a topoisomerase I assay, one of the analogs (4-nitrobenzyl) was shown to inhibit the ability of this enzyme to relax supercoiled pBR322 DNA, at a similar concentration to the clinically-approved active metabolite SN-38. Cyclic voltammetry detailed the reductive nature of the analogs, and was used to infer the potential of these compounds to serve as hypoxia-targeting prodrugs. The electrochemical results also validated the quasi-reversible nature of the first reduction step, and served as a proof-of-principle that hypoxia-targeting prodrugs of SN-38 can participate in a redox-futile cycle, the proposed mechanism of activation and targeting. Chemical reduction of the 4-nitrobenzyl analog led to the formation/release of SN-38 and validated the prodrug ability of the C-10 substituted derivative.
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A. Al-Salmi, Fawziah, Abdulmohsen H Alrohaimi, Mohammed El Behery, et al. "Anticancer Studies of Newly Synthesized Thiazole Derivatives: Synthesis, Characterization, Biological Activity, and Molecular Docking." Crystals 13, no. 11 (2023): 1546. http://dx.doi.org/10.3390/cryst13111546.
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Thiazole and its derivatives have received a lot of attention from researchers due to its wide biological, pharmacological, and anticancer properties. A novel series of 2-[2-[4-Hydroxy-3-substituted benzylidene hydrazinyl]-thiazole-4[5H]-ones (4a–c) and acetoxy derivative (5) were synthesized via using thiosemicarbazones (2a–c). The structure of the thiazole derivatives (4a–c) and 5 in these compounds was confirmed by spectroscopic techniques (IR and NMR), as well as elemental investigations. The synthesized derivatives biological activity was assessed based on their capacity to suppress the growth of the cancer cell lines MCF-7 and HepG2, as well as to halt the cell cycle and trigger apoptosis. Among the synthesized thiazole derivatives, compound 4c was found the most active derivative, with inhibitory concentrations IC50 = 2.57 ± 0.16 and 7.26 ± 0.44 µM in MCF-7 and HepG2, respectively, compared to Staurosporine as the standard drug with IC50 6.77 ± 0.41 and 8.4 ± 0.51 µM, respectively. Additionally, compound 4c blocked vesicular endothelial growth factor receptor-2 (VEGFR-2), according to our results (IC50 = 0.15 µM), compared to Sorafenib (IC50 = 0.059 µM) as the standard drug. Moreover, compound 4c induced cell cycle arrest at the G1/S phase, increasing the percentage and accumulation of cancer cells (DNA content) in the pre-G1 phase by 37.36% in MCF-7 cancer cells compared to untreated MCF-7 cells at 2.02%. Also, compound 4c increased the percentage of early and late apoptosis from 0.51% and 0.29%, respectively, in the case of the MCF-7 untreated control sample to 22.39% and 9.51%, respectively, in the MCF-7 treated sample. Furthermore, molecular docking studies of compounds 4a–c and 5 were conducted with four key proteins (aromatase, epidermal growth factor receptor (EGFR), cyclin-dependent kinase 2 (CDK2), and B-cell lymphoma 2 (Bcl-2)) that stimulate the growth, proliferation, and development of cancer cells. Compound 4c exhibited good docking scores with a promising and potential binding affinity toward the active site of selected docked proteins. According to these results, compound 4c showed efficient cytotoxic activity against the tested cancer cells.
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Mikra, Chrysoula, Maria Bairaktari, Marina-Theodora Petridi, Anastasia Detsi, and Konstantina C. Fylaktakidou. "Green Process for the Synthesis of 3-Amino-2-methyl-quinazolin-4(3H)-one Synthones and Amides Thereof:DNA Photo-Disruptive and Molecular Docking Studies." Processes 10, no. 2 (2022): 384. http://dx.doi.org/10.3390/pr10020384.
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Eleven 3-amino-2-methyl-quinazolin-4(3H)-ones have been synthesized, in good to excellent yields, via their corresponding benzoxazinones using an efficient tandem microwave-assisted green process. Representative acetamides have been thermally derived from their functional free 3-amino group, whereas for the synthesis of various arylamides, a novel green microwave-assisted protocol has been developed, which involved the attack of hydrazides on benzoxazinones. Eight out of the eleven 3-amino-2-methyl-quinazolin-4(3H)-ones were found photo-active towards plasmid DNA under UVB, and four under UVA irradiation. Amongst all acetamides, only the 6-nitro derivative retained activity both under UVB and UVA irradiation, whereas the 6-bromo-substituted one was active only under UVB. 3-arylamido-6-bromo derivatives exhibited dramatically decreased photo-activity; however, all 3-arylamido-6-nitro compounds developed extraordinary activity, even at concentrations as low as 1μM, which was enhanced compared to their parent 3-amino-2-methyl-6-nitro-quinazolinone. Molecular docking studies were indicative of satisfactory binding to DNA and correlated to the presented photo-activity. Since quinazolinones are known “privileged” pharmacophores for anticancer and antimicrobial activities, the present study gives information on turning “on” and “off” photosensitization on various derivatives which are often used as synthones for drug development, when chromophores and auxochromes are incorporated or being functionalized. Thus, certain compounds may lead to the development of novel photo-chemo or photodynamic therapeutics.
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Kulikova, Tatjana, Igor Shiabiev, Pavel Padnya, et al. "Impedimetric DNA Sensor Based on Electropolymerized N-Phenylaminophenothiazine and Thiacalix[4]arene Tetraacids for Doxorubicin Determination." Biosensors 13, no. 5 (2023): 513. http://dx.doi.org/10.3390/bios13050513.
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Electrochemical DNA sensors are highly demanded for fast and reliable determination of antitumor drugs and chemotherapy monitoring. In this work, an impedimetric DNA sensor has been developed on the base of a phenylamino derivative of phenothiazine (PhTz). A glassy carbon electrode was covered with electrodeposited product of PhTz oxidation obtained through multiple scans of the potential. The addition of thiacalix[4]arene derivatives bearing four terminal carboxylic groups in the substituents of the lower rim improved the conditions of electropolymerization and affected the performance of the electrochemical sensor depending on the configuration of the macrocyclic core and molar ratio with PhTz molecules in the reaction medium. Following that, the deposition of DNA by physical adsorption was confirmed by atomic force microscopy and electrochemical impedance spectroscopy. The redox properties of the surface layer obtained changed the electron transfer resistance in the presence of doxorubicin due to its intercalating DNA helix and influencing charge distribution on the electrode interface. This made it possible to determine 3 pM–1 nM doxorubicin in 20 min incubation (limit of detection 1.0 pM). The DNA sensor developed was tested on a bovine serum protein solution, Ringer–Locke’s solution mimicking plasma electrolytes and commercial medication (doxorubicin-LANS) and showed a satisfactory recovery rate of 90–105%. The sensor could find applications in pharmacy and medical diagnostics for the assessment of drugs able to specifically bind to DNA.
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Xi, Wenli, Hua Sun, Kenneth F. Bastow, Zhiyan Xiao, and Kuo-Hsiung Lee. "Identification of Novel 4′-O-Demethyl-epipodophyllotoxin Derivatives as Antitumor Agents Targeting Topoisomerase II." Molecules 27, no. 15 (2022): 5029. http://dx.doi.org/10.3390/molecules27155029.
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C4 variation of 4′-O-demethyl-epipodophyllotoxin (DMEP) is an effective approach to optimize the antitumor spectra of this compound class. Accordingly, two series of novel DMEP derivatives were synthesized, and as expected, the antitumor spectra of these derivatives varied with different C4 substituents. Notably, most compounds showed significant inhibition against the etoposide (2)-resistant KBvin cells. Four of the compounds (11, 18, 27 and 28) induced protein-linked DNA break (PLDB) levels higher than those of GL-331 (6) and 2, and are assumed to be topoisomerase II (topo II) poisons more potent than 6 and 2. Compound 28, a potent topo II poison highly effective against KBvin cells, was further evaluated with a panel of tumor cells and was most active against HepG2. This compound also exhibited apparent in vivo antitumor efficacy in hepatoma 22 (H22) mouse model. The results indicated that C4 derivation of DMEP is a feasible approach to identify potent topo II inhibitors with optimized antitumor profiles.
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FERREIRA, PAULO MICHEL PINHEIRO, PATRICIA MARÇAL DA COSTA, ARINICE DE MENEZES COSTA, et al. "Cytotoxic and toxicological effects of phthalimide derivatives on tumor and normal murine cells." Anais da Academia Brasileira de Ciências 87, no. 1 (2015): 313–30. http://dx.doi.org/10.1590/0001-3765201520130345.
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Eleven phthalimide derivatives were evaluated with regards to their antiproliferative activity on tumor and normal cells and possible toxic effects. Cytotoxic analyses were performed against murine tumors (Sarcoma 180 and B-16/F-10 cells) and peripheral blood mononuclear cells (PBMC) using MTT and Alamar Blue assays. Following, the investigation of cytotoxicity was executed by flow cytometry analysis and antitumoral and toxicological potential by in vivo techniques. The molecules 3b, 3c, 4 and 5 revealed in vitro cytotoxicity against Sarcoma 180, B-16/F-10 and PBMC. Since compound 4 was the most effective derivative, it was chosen to detail the mechanism of action after 24, 48 and 72 h exposure (22.5 and 45 µM). Sarcoma 180 cells treated with compound 4 showed membrane disruption, DNA fragmentation and mitochondrial depolarization in a time- and dose-dependent way. Compounds 3c, 4 and 5 (50 mg/kg/day) did not inhibit in vivotumor growth. Compound 4-treated animals exhibited an increase in total leukocytes, lymphocytes and spleen relative weight, a decreasing in neutrophils and hyperplasia of spleen white pulp. Treated animals presented reversible histological changes. Molecule 4 had in vitro antiproliferative action possibly triggered by apoptosis, reversible toxic effects on kidneys, spleen and livers and exhibited immunostimulant properties that can be explored to attack neoplasic cells.
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Bateman, Stuart A., David P. Kelly, Jonathan M. White, and Roger F. Martin. "DNA Binding Compounds. VII. Synthesis, Characterization and DNA Binding Capacity of 1,2-Dicarba-closo-dodecaborane Bibenzimidazoles Related to the DNA Minor Groove Binder Hoechst 33258." Australian Journal of Chemistry 52, no. 4 (1999): 291. http://dx.doi.org/10.1071/c98148.
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A series of bibenzimidazole derivatives based on the known DNA minor groove binder Hoechst 33258 have been prepared to include a 1,2-dicarba-closo-dodecaborane cage for potential use in boron neutron capture therapy (BNCT). The carborane derivatives (5){(7) were chosen to reduce the steric inhibition of minor groove DNA binding displayed by the previously prepared carborane ligand (4). The synthesis and preliminary DNA binding studies of these bibenzimidazole derivatives are presented herein.
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Ramakrishna, C., and G. V. Subbareddy. "Synthesis Docking Studies and Antitubercular Activity of Ofloxacin Scaffold using Blanc Reaction." Asian Journal of Chemistry 34, no. 3 (2022): 644–50. http://dx.doi.org/10.14233/ajchem.2022.23584.
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Synthesis, molecular docking and characterization of ofloxacin derivatives and in vitro evaluation for their antitubercular action were carried out. Synthesis ofloxacin derivatives viz. O+TRI, O+MEL, O+NAP, O+SUL, O+METF, O+IBU, O+ASP, O+DNP, O+SSA, O+PH, O+MC (where TRI = trimethoprim, MEL = meloxicam, NAP = naproxen, SUL = sulfamethoxazole, METF = metformin, IBU = ibuprofen, ASP = aspirin, DNP = 2,4-dinitrophenyl hydrazine, SSA = 5-sulpho salicylic acid, PH = phenyl hydrazine, MC = 7-hydroxy-4-methyl coumarin) were carried using Blanc reaction and purified by using of ethanol by recrystallization. The reaction products consist of methylene group linkage between two moieties and the molecules were characterized by analytical methods TLC, solubility, melting point, spectroscopic methods (FT-IR, mass and 1H NMR, 13C NMR). In silico methods were adopted for synthetic derivatives by Autodock vina software. Determined physico-chemical parameters (in silico studies) and docking studies have been performed using protein (5BS8) with designed ligands, binding energy scores were noted for different derivatives. Derivatives O+TRI, O+NAP shown good activity at 0.8 μg/mL. In docking studies, all the compounds shown promising results when compared to standard drugs.
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Mohamed, Heba A. E., and Hossa F. Al-Shareef. "Design, Synthesis, Anti-Proliferative Evaluation and Cell Cycle Analysis of Hybrid 2-Quinolones." Anti-Cancer Agents in Medicinal Chemistry 19, no. 9 (2019): 1132–40. http://dx.doi.org/10.2174/1871520619666190319142934.
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Background: Quinolones are a significant group of nitrogen heterocyclic compounds that exist in therapeutic agents, alkaloids, and synthetic small molecules that have important biological activities. A wide range of quinolones have been used as antituberculosis, antibacterial, anti-malarial, antifungal, anticonvulsant, anticancer agents and urease inhibitors. Methods: Ethyl 3,3-disubstituted-2-cyano propionates containing hybride quinolones derivatives were synthesized by the reaction of 1-amino-7-hydroxy-4-methylquinolin-2(1H)-one and its dibromo derivative with α, β-unsaturated carbonyl in ethanol. Results: A novel series of hybrid 2-quinolone derivatives was designed and synthesized. The compounds structures were confirmed using different spectroscopic methods and elemental analysis. The cytotoxic activities of all the compounds were assessed against HepG2 cell line in comparison with doxorubicin as a standard drug. Conclusion: Most compounds revealed superior anti-proliferative activity than the standard. Compound 4b, is the most active compound (IC50 = 0.39mM) compared with doxorubicin (IC50 = 9.23mM). DNA flow cytometric analysis of compound 4b showed cell cycle arrest at G2/M phase with a concomitant increase of cells in apoptotic phase. Dual annexin-V/ propidium iodide staining assay of compound 4b revealed that the selected candidate increased the apoptosis of HepG-2 cells more than control.
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Durchschein, Christin, Antje Hufner, Beate Rinner, et al. "Synthesis of Novel Shikonin Derivatives and Pharmacological Effects of Cyclopropylacetylshikonin on Melanoma Cells." Molecules 23, no. 11 (2018): 2820. http://dx.doi.org/10.3390/molecules23112820.
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Despite much research in the last centuries, treatment of malignant melanoma is still challenging because of its mostly unnoticeable metastatic spreading and aggressive growth rate. Therefore, the discovery of novel drug leads is an important goal. In a previous study, we have isolated several shikonin derivatives from the roots of Onosma paniculata Bureau & Franchet (Boraginaceae) which evolved as promising anticancer candidates. β,β-Dimethylacrylshikonin (1) was the most cytotoxic derivative and exhibited strong tumor growth inhibitory activity, in particular, towards melanoma cells. In this study, we synthesized eighteen novel shikonin derivatives in order to obtain compounds which exhibit a higher cytotoxicity than 1. We investigated their cytotoxic potential against various melanoma cell lines and juvenile skin fibroblasts. The most active compound was (R)-1-(1,4-dihydro-5,8-dihydroxy-1,4-dioxonaphthalen-2-yl)-4-methylpent-3-enyl cyclopropylacetate (cyclopropylacetylshikonin) (6). It revealed significant stronger tumor growth inhibitory activity towards two melanoma cell lines derived from metastatic lesions (WM164 and MUG-Mel2). Further investigations have shown that 6 induced apoptosis caspase-dependently, increased the protein levels of cleaved PARP, and led to double-stranded DNA breaks as shown by phosphorylation of H2AX. Cell membrane damage and cell cycle arrest were not observed.
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Melo, P. S., N. Durán, and M. Haun. "Derivatives of dehydrocrotonin, a diterpene lactone isolated fromCroton cajucara: cytotoxicity in rat cultured hepatocytes and in V79 cells." Human & Experimental Toxicology 21, no. 5 (2002): 281–88. http://dx.doi.org/10.1191/0960327102ht246oa.
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Derivatives of dehydrocrotonin (DHC; Compound I) with different anti-ulcerogenic properties but less toxicity were produced by reducing the cyclohexenone moiety of DHC with NaBH4 (Compound II), reducing the cyclohexenone and lactone moieties with LiAlH4 (Compound III) and transforming the lactone moiety into an amide (Compound IV) using dimethylamine. Derivatives of DHC were assayed in cultured hepatocytes and V79 fibroblasts. Three independent endpoints assays for cytotoxicity were used, namely, the DNA content, tetrazolium reduction (MTT) and neutral red uptake (NRU). Compound III was less toxic than the other DHC derivatives in both cell cultures. IC50values ranging from 250 to 600 m M were obtained for Compounds II and IV in the NRU and DNA content tests evaluated in 4-hour hepatocyte cultures. Although Compound II showed relatively low cytotoxicity in rat hepatocytes based on the NRU and DNA content assays, a very high toxicity (IC50=10 m M) was observed in the MTT test. Metabolites of Compound II in conditioned medium from 4-hour old hepatocyte cultures enhanced the MTT-reducing ability of V79 fibroblasts. The cytotoxicity of the derivatives was greater in recently isolated hepatocytes (only a 4-hour incubation for cell attachment prior to treating with the derivatives) than in hepatocytes previously cultured (24-hour incubation) before the treatment. Thus, aging reduced the cytotoxic effects of DHC derivatives in isolated hepatocytes, suggesting that P450-mediated biotransformation of such derivatives may lead to the formation of more toxic metabolites.
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Lee, Kuo-Hsiung, Makoto Miyahara, Yoshiki Kashiwada, Xin Guo, Hong-Xing Chen, and Yung-Chi Cheng. "Nitrosourea Derivatives of 3',4'-Didemethoxy-3',4'-dioxo-4-deoxypodophyllotoxin and Urea Derivatives of 4'-O-Demethylpodophyllotoxin as Potent Inhibitors of Human DNA Topoisomerase." HETEROCYCLES 39, no. 1 (1994): 361. http://dx.doi.org/10.3987/com-94-s(b)41.
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Tang, Bikui, Meili Wei, Qun Niu, et al. "Antimicrobial Activity of Quinazolin Derivatives of 1,2-Di(quinazolin-4-yl)diselane against Mycobacteria." BioMed Research International 2017 (2017): 1–7. http://dx.doi.org/10.1155/2017/5791781.
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Mycobacterium tuberculosis (M. tuberculosis) is one of the leading causes of morbidity and mortality. Currently, the emergence of drug resistance has an urgent need for new drugs. In previous study, we found that 1,2-di(quinazolin-4-yl)diselane (DQYD), a quinazoline derivative, has anticancer activities against many cancers. However, whether DQYD has the activity of antimycobacterium is still little known. Here our results show that DQYD has a similar value of the minimum inhibitory concentration with clinical drugs against mycobacteria and also has the ability of bacteriostatic activity with dose-dependent and time-dependent manner. Furthermore, the activities of DQYD against M. tuberculosis are associated with intracellular ATP homeostasis. Meanwhile, mycobacterium DNA damage level was increased after DQYD treatment. But there was no correlation between survival of mycobacteria in the presence of DQYD and intercellular reactive oxygen species. This study enlightens the possible benefits of quinazoline derivatives as potential antimycobacterium compounds and furtherly suggests a new strategy to develop new methods for searching antituberculosis drugs.
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Munir, Samman, Mohsin Khurshid, Matloob Ahmad, Usman Ali Ashfaq, and Magdi E. A. Zaki. "Exploring the Antimicrobial and Pharmacological Potential of NF22 as a Potent Inhibitor of E. coli DNA Gyrase: An In Vitro and In Silico Study." Pharmaceutics 14, no. 12 (2022): 2768. http://dx.doi.org/10.3390/pharmaceutics14122768.
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Toward the search for novel antimicrobial agents to control pathogenic E. coli-associated infections, a series of novel norfloxacin derivatives were screened for antimicrobial activities. The norfloxacin derivative, 1-ethyl-6-fluoro-7-(4-(2-(2-(3-hydroxybenzylidene)hydrazinyl)-2-oxoethyl)piperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid (NF22) demonstrated excellent antibacterial activities against E. coli ATCC 25922 (MIC = 0.0625 μg/mL) and MDR E. coli 1–3 (MIC = 1, 2 and 1 µg/mL). The time-kill kinetic studies have demonstrated that the NF22 was advantageous over norfloxacin and ciprofloxacin in killing the control and MDR E. coli strains. The checkerboard assay showed that NF22 in combination with tetracycline had a synergistic effect against the E. coli strains. The experimental findings are supported by molecular modeling studies on DNA gyrase, explaining the interactions involved for compound NF22, compared to norfloxacin and ciprofloxacin. Further, the compound was also evaluated for various pharmacokinetics (absorption, metabolism, distribution, toxicity and excretion) as well as drug-likeness properties. Our data have highlighted the potential of norfloxacin by restoring its efficacy against E. coli which could lead to the development of new antimicrobial agents.
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El-Metwally, Souad A., Ali K. Khalil, Abeer M. El-Naggar, and Wael M. El-Sayed. "Novel Tetrahydrobenzo [b] Thiophene Compounds Exhibit Anticancer Activity through Enhancing Apoptosis and Inhibiting Tyrosine Kinase." Anti-Cancer Agents in Medicinal Chemistry 18, no. 12 (2019): 1761–69. http://dx.doi.org/10.2174/1871520618666180813120558.
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Background: Developing new chemotherapeutic agents with molecular targets, larger margin of safety against normal cells and low cost is the target many scientists try to achieve. Objective: The present study was undertaken to investigate the anticancer activity of a novel series of thiophene compounds and the molecular mechanisms associated. Method: A series of novel heterocyclic compounds including pyrimidine derivatives (2, 3, 4, 5 8, 11, 12, 13, 14, and 15), thiophene derivatives (6, 7, and 10) and oxoisothiazolidine derivative (9) was synthesized from 4,5,6,7- tetrahydrobenzo[b] thiophene (1). The newly synthesized derivatives along with the parent compound were evaluated for their anticancer activity against human HepG2, MCF7 and HCT116 cell lines and compared to doxorubicin as a reference drug. Results: Compound 7 was very selective in targeting only the colon cells. Compounds 1, 5, and 12 showed strong cytotoxic activities against the 3 cell lines at 6-16 µM without any apparent toxicity to the normal fibroblasts WI-38. They had DNA affinity at 29-36 µM. The three compounds enhanced apoptosis to varying degrees elevating the expression of Bax, caspase 9 and caspase 3 in HepG2. Compound 5 was the most potent analogue and was superior to the standard drug used in upregulating the apoptotic genes and inhibiting tyrosine kinase at 1 µM. The IC50 value for compound 5 against TK was 296 nM. Conclusion: Taken together, this study presents some thiophene scaffolds as auspicious hits for further optimization as specific antiproliferative agents against cancer cells and promising tyrosine kinase inhibitors at nanomolar concentrations.
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Garozzo, Adriana, Christian CC Cutri, Christophe Pannecouque, Angelo Castro, Francesco Guerrera, and Erik De Clercq. "Isothiazole Derivatives as Antiviral Agents." Antiviral Chemistry and Chemotherapy 18, no. 5 (2007): 277–83. http://dx.doi.org/10.1177/095632020701800503.
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We recently described the synthesis and antiviral activity of the compounds 5-phenyl-3-(4-cyano-5-phenylisothiazol-3-yl) disulphanyl-4-isothiazole-carbonitrile and S-(4-cyano-5-phenylisothiazol-3-yl)- O-ethyl thiocarbonate, which were found to be effective against both HIV-1 (IIIB) and HIV-2 (ROD). We have now evaluated these compounds against both RNA and DNA viruses, obtaining high selectivity indexes for poliovirus 1 (SI: 223 and 828, respectively) and Echovirus 9 (SI: 334 and 200, respectively). In our previous studies, 3-methylthio-5-(4- OBn-phenyl)-4-isothiazolecarbo-nitrile was found to exhibit a broad spectrum of action against picornaviruses, we therefore selected this compound and S-(4-cyano-5-phenylisothiazol-3-yl)- O-ethyl thiocarbonate as the model for the synthesis of a new isothiazole derivative, S-[4-cyano-5-(4- OBn-phenyl)isothiazol-3-yl]- O-ethyl thiocarbonate. This compound was evaluated against picornaviruses, measles virus, HIV-1 (IIIB) and HIV-2 (ROD), and some DNA viruses (adenovirus type 2 and herpes simplex virus type 1). The compound was shown to be active against rhinoviruses 2, 39, 86 and 89, Coxsackie B1 and measles virus.
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Nikšić-Franjić, Ivana, Dijana Pavlović Saftić, Vilko Smrečki, et al. "Transition Metals Coordination by Bis-imidazole-calix[4]arene Ligands with and Without Pyrene Units Grafted at the Large Rim." International Journal of Molecular Sciences 25, no. 20 (2024): 11314. http://dx.doi.org/10.3390/ijms252011314.
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Herein, the presented results show that previously studied DNA/RNA-interacting bis-imidazole-calix[4]arene systems can, in aqueous solutions, efficiently bind a series of biorelevant transition metal cations by coordination with the two imidazole arms at the small rim of their macrocyclic basket. The SCXRD and NMR results structurally characterised the complexes formed by referent bis-imidazole-calix[4]arene with Cu2+ and Zn2+. In solid-state (crystal), the bis-anilino derivative/Cu2+ complex, only upon exposure to the air, undergoes intramolecular dehydrogenative coupling of two neighbouring aniline units, yielding an azo bridge at the large rim of the calix[4]arene basket. In the biorelevant aqueous solution, the comparison of fluorometric titrations of referent calix[4]arene, with its analogues having one or two pyrene units grafted at the opposite (large) rim, revealed moderate-to-strong affinity towards transition metal cations, and, more importantly, a strong impact of pyrene on the binding affinity towards some cations. The pyrene arm(s) significantly diminished the affinity of the calix[4]arene-imidazole ligand towards Cu+ and strongly increased the affinity towards divalent Co2+ and Cd2+ cations. Moreover, the fluorometric response of some studied derivatives was strappingly sensitive to cation type. Since the counter-anion plays only a marginal role, such a change in selectivity is attributed to the intramolecular interaction of pyrene(s) with the calix[4]arene-imidazole system, sterically controlling the metal cation binding site.
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Gutiérrez, Joyce E., Esteban Fernandez-Moreira, Miguel A. Rodríguez, et al. "Novel 7-Chloro-(4-thioalkylquinoline) Derivatives: Synthesis and Antiproliferative Activity through Inducing Apoptosis and DNA/RNA Damage." Pharmaceuticals 15, no. 10 (2022): 1234. http://dx.doi.org/10.3390/ph15101234.
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A series of 78 synthetic 7-chloro-(4-thioalkylquinoline) derivatives were investigated for cytotoxic activity against eight human cancer as well as 4 non-tumor cell lines. The results showed, with some exceptions, that sulfanyl 5–40 and sulfinyl 41–62 derivatives exhibited lower cytotoxicity for cancer cell lines than those of well-described sulfonyl N-oxide derivatives 63–82. As for compound 81, the most pronounced selectivity (compared against BJ and MRC-5 cells) was observed for human cancer cells from HCT116 (human colorectal cancer with wild-type p53) and HCT116p53−/− (human colorectal cancer with deleted p53), as well as leukemia cell lines (CCRF-CEM, CEM-DNR, K562, and K562-TAX), lung (A549), and osteosarcoma cells (U2OS). A good selectivity was also detected for compounds 73 and 74 for leukemic and colorectal (with and without p53 deletion) cancer cells (compared to MRC-5). At higher concentrations (5 × IC50) against the CCRF-CEM cancer cell line, we observe the accumulation of the cells in the G0/G1 cell phase, inhibition of DNA and RNA synthesis, and induction of apoptosis. In addition, X-ray data for compound 15 is being reported. These results provide useful scientific data for the development of 4-thioalkylquinoline derivatives as a new class of anticancer candidates.
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Rozmer, Zsuzsanna, Aline Bernardes, Caridad N. Pérez, and Pál Perjési. "Study on the Interaction of 4'-Hydroxychalcones and their Mannich Derivatives with Calf Thymus DNA by TLC and Spectroscopic Methods, a DNA Cleavage Study." Open Medicinal Chemistry Journal 14, no. 1 (2020): 122–31. http://dx.doi.org/10.2174/1874104502014010122.
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Background: Phenolic Mannich bases derived from hydroxychalcones show remarkable cytotoxic potencies towards cancer cell lines. However, the exact mechanism of action is still partially uncleared. Objective: Interaction of two hydroxychalcones and their Mannich derivatives with calf thymus DNA (ctDNA) has been investigated. Methods: Thin-layer chromatography and UV-Vis spectroscopic method were used for studying the interaction. The binding constant has been determined by UV-Vis spectrophotometric titration. The DNA cleavage activity of the compounds was studied by agarose gel electrophoresis. Results: Interaction of the compounds with ctDNA exhibited relatively high intrinsic binding constant (4-5x104 M-1). The results indicate existence of weak, non-covalent interactions between the investigated derivatives with ctDNA. Some compounds showed a slight DNA cleavage activity with pBR322. Conclusion: The obtained results provide additional knowledge on the previously documented cytotoxicity against tumor cell lines of the hydroxychalcones and their Mannich-derivatives.
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Finiuk, N. S., I. I. Ivasechko, O. Yu Klyuchivska, H. M. Kuznietsova, V. K. Rybalchenko, and R. S. Stoika. "Cytotoxic action of maleimide derivative 1-(4-Cl-benzyl)-3-chloro-4-(CF(3)-phenylamino)-1H-pyrrole-2,5-dione toward mammalian tumor cells and its capability to interact with DNA." Ukrainian Biochemical Journal 92, no. 4 (2020): 55–62. http://dx.doi.org/10.15407/ubj92.04.055.
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Barut, Burak, Ayşenur Sofuoğlu, Zekeriya Biyiklioglu, and Arzu Özel. "The water soluble peripherally tetra-substituted zinc(ii), manganese(iii) and copper(ii) phthalocyanines as new potential anticancer agents." Dalton Transactions 45, no. 36 (2016): 14301–10. http://dx.doi.org/10.1039/c6dt02720b.
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In this study, [2-(2-morpholin-4-ylethoxy)ethoxy] group substituted zinc(ii), manganese(iii) and copper(ii) phthalocyanines 2–4 and their water soluble derivatives 2a, 3a and 4a were synthesized and the interactions of compounds 2a, 3a and 4a with CT-DNA and supercoiled pBR322 plasmid DNA were investigated.
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Locatelli, Giada A., Monica Savio, Luca Forti, et al. "Inhibition of mammalian DNA polymerases by resveratrol: mechanism and structural determinants." Biochemical Journal 389, no. 2 (2005): 259–68. http://dx.doi.org/10.1042/bj20050094.
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Resveratrol, a natural compound found in many dietary plants and in red wine, plays an important role in the prevention of many human pathological processes, including inflammation, atherosclerosis and carcinogenesis. We have shown that the antiproliferative activity of resveratrol correlated with its ability to inhibit the replicative pols (DNA polymerases) α and δ in vitro [Stivala, Savio, Carafoli, Perucca, Bianchi, Maga, Forti, Pagnoni, Albini, Prosperi and Vannini (2001) J. Biol. Chem. 276, 22586–22594]. In this paper, we present the first detailed biochemical investigation on the mechanism of action of resveratrol towards mammalian pols. Our results suggest that specific structural determinants of the resveratrol molecule are responsible for selective inhibition of different mammalian pols, such as the family B pol α and the family X pol λ. Moreover, the resveratrol derivative trans-3,5-dimethoxy-4-hydroxystilbene, which is endowed with a strong antiproliferative activity (Stivala et al., 2001), can inhibit pols α and λ and also suppress the in vitro SV40 DNA replication. The potency of inhibition is similar to that of aphidicolin, an inhibitor of the three replicative pols α, δ and ε. Our findings establish the necessary background for the synthesis of resveratrol derivatives having more selective and potent antiproliferative activity.
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Wang, Jun, Guan-Cheng Xu, Yan-Ping Zhang, et al. "Copper(ii) complexes with 4-acyl pyrazolone derivatives and diimine coligands: synthesis, structural characterization, DNA binding and antitumor activity." New Journal of Chemistry 43, no. 6 (2019): 2529–39. http://dx.doi.org/10.1039/c8nj02695e.
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Kubota, Yutaka, Nobuhide Ishizaki, Yuri Kaneda та ін. "Synthesis and Antiviral Evaluation of 4'-alkoxy Analogues of 9-(β-D-xylofuranosyl)adenine". Antiviral Chemistry and Chemotherapy 19, № 5 (2009): 201–12. http://dx.doi.org/10.1177/095632020901900503.
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Background: Motivated by the reported biological activity of 9-(β-D-xylofuranosyl)adenine (xylo-A), the synthesis of its 4'-alkoxy analogues was carried out. Methods: The starting material 9-(3-deoxy-β-D-glycero-pento–3-enofuranosyl)adenine (1) was prepared from adenosine. Compound 1 was converted to the 2',5'-bis-0–(tert-butyldimethylsilyl) derivative (2) and then to the N6-pivaloyl derivative (3). When 3 was reacted with meta- chloroperbenzoic acid in the presence of a series of alcohols, the β-D-isomer of the respective 4'-alkoxy derivative was obtained exclusively in high yield. Deprotection of these products led to the isolation of the desired 4'alkoxy analogues (8a-I) of xylo-A. Results: Antiviral evaluation revealed that none of these analogues showed inhibitory activity against a wide variety of DNA and RNA viruses. Conclusions: We assume that conformational difference of the sugar moiety of 8a-1 from that of xylo-A could be attributable to their inactivity.
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Ananto, Agus Dwi, Harno Dwi Pranowo, Winarto Haryadi, and Niko Prasetyo. "Exploring The Inhibition of SARS-COV-2 PLpro: Docking and Molecular Dynamics Simulation of Flavonoid in Red Fruit Papua and Its Derivatives." Molekul 19, no. 3 (2024): 581. https://doi.org/10.20884/1.jm.2024.19.3.11717.
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In early 2024, Covid-19 witnessed a substantial decline in cases. Nevertheless, with lingering cases and fatalities persisting, it remains crucial to focus on research to develop patented medicines to inhibit the spread of this virus effectively. This study focuses on the Papain-like protease (PLpro) of SARS-CoV-2 because of its crucial role in the viral life cycle, where it is vital for processing precursor proteins into functional components required for viral replication and propagation. This study investigated the inhibitory potential of flavonoid compounds derived from red fruit (Pandanus conoideus Lam) and their derivatives against SARS-CoV-2 PLpro. Employing an in silico approach through molecular docking and MD simulation, internal validation was conducted by redocking the native ligand 100 times, resulting in an average RMSD of 0.228. The Molecular Docking stage conducted for all flavonoid compounds found in red fruit revealed that Quercetin 3′-glucoside exhibited a binding energy of -8.2440 Kcal/mol, surpassing its comparators, remdesivir and paxlovid, which recorded binding energies of -8.2590 Kcal/mol and -7.2170 Kcal/mol, respectively. Consequently, Quercetin 3′-glucoside was selected as a reference compound for identifying derivative compounds. Subsequently, a derivative compound coded DN5 (2-hydroxy-5-(3,5,7-trihydroxy-4-oxo-4H-chromen-2-yl)phenyl 2-methoxybenzoate) was obtained, demonstrating a higher binding energy than the reference compound, remdesivir, and paxlovid, with a value of -8.9300 Kcal/mol. Molecular dynamic simulations over 100 ns at 300 K further validated the stability of DN5's structure, supported by the presence of hydrogen bonds, van der Waals bonds, and several other bonds, underscoring its potential to inhibit SARS-CoV-2 PLpro and positioning it as a promising candidate for drug development. Keywords: Docking, MD Simulation, red fruit, SARS-CoV-2 PLpro