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Aksic, Jelena, Marija Gencic, and Niko Radulovic. "Recent updates in the development of mettallocenes with antimalarial activity." Facta universitatis - series: Physics, Chemistry and Technology 18, no. 1 (2020): 1–37. http://dx.doi.org/10.2298/fupct2001001a.
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Great progress in the fight against malaria has been made in the last decade. Nevertheless, the development of resistance to almost all commonly used antimalarial drugs poses a major threat to the sustainability of this progress and highlights the need for the discovery of novel potent and inexpensive antimalarials to stay one step ahead. After the finding of ferrocene-containing analog of chloroquine - ferroquine, that can overcome Plasmodium resistance, a ?big-bang? in the metallocene antimalarials research has occurred. This review describes in detail the most recent advances in this important field of medicinal chemistry. Even though it is quite hard to beat ferroquine, it seems that this could be succeeded by suitable modifications in the structure of ferroquine, by the introduction of ? second metal center or through joining metallocenes with two or more proven antimalarial motifs into a single molecule.
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SMITH, PAUL W., THIERRY T. DIAGANA, and BRYAN K. S. YEUNG. "Progressing the global antimalarial portfolio: finding drugs which target multiple Plasmodium life stages." Parasitology 141, no. 1 (June 10, 2013): 66–76. http://dx.doi.org/10.1017/s0031182013000747.
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SUMMARYThe number of novel antimalarial candidates entering preclinical development has seen an increase over the last several years. Most of these drug candidates were originally identified as hits coming from screening large chemical libraries specifically targeting the asexual blood stages of Plasmodium falciparum. Indeed, a large proportion of the current antimalarial arsenal has mainly targeted the asexual blood stage which is responsible for clinical symptoms of the disease. However, as part of the eradication agenda and to address resistance, any next-generation antimalarial should have additional activity on at least one other parasite life stage, i.e. gametocytocidal and/or tissue schizonticidal activity. We have applied this approach by screening compounds with intrinsic activity on asexual blood stages in assays against sexual and liver stages and identified two new antimalarial chemotypes with activity on multiple parasite life stages. This strategy can be expanded to identify other chemical classes of molecules with similar activity profiles for the next generation antimalarials. The following review summarizes the discovery of the spiroindolones and imidazolopiperazine classes of antimalarials developed by the NGBS consortium (Novartis Institute for Tropical Diseases, Genomic Institute of the Novartis Research Foundation, Biomedical Primate Research Center, and the Swiss Tropical and Public Health Institute) currently in clinical trials.
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Choudhary, Amit, Manish Sinha, Arti Devi, Shammy Jindal, and Kamya Goyal. "A Review on Antimalarial 1,2,4-Trioxane Derivatives." Journal of Drug Delivery and Therapeutics 10, no. 4-s (August 15, 2020): 240–53. http://dx.doi.org/10.22270/jddt.v10i4-s.4268.
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Malaria in recent years becomes a major health hitch globally due to the surfacing of multidrug-resistant strains of Plasmodium falciparum parasite. In recent times, artemisinin (ART)-based drugs and combination therapies become the drugs of preference for the treatment and prophylaxis of resistant P. falciparum malaria. Endoperoxide compounds natural, semi-synthetic or synthetic signifying a massive number of antimalarial agents which possess a wide structural miscellany with needed antimalarial effectiveness against resistant P. falciparum malaria. The 1,2,4-trioxane ring system deficient the lactone ring which constitutes the most significant endoperoxide structural scaffold which is believed to be the key pharmacophoric moiety and is principally responsible for the pharmacodynamic potential of endoperoxide-based antimalarials. This becomes the main reason for the research related to endoperoxide particularly 1,2,4-trioxane-, 1,2,4-trioxolane- and 1,2,4,5-tetraoxane-based scaffolds gaining the noteworthy interest in recent years for developing antimalarial drugs against resistant malaria. In this paper, a comprehensive endeavour has been made to review the development of different endoperoxide antimalarial agents and structural diversity of endoperoxide molecules derived from 1,2,4-trioxane- based structural scaffolds.
Keywords: Endoperoxide; 1,2,4-trioxane; pharmacophores; artemisinin; antimalarial.
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Biddau, Marco, and Lilach Sheiner. "Targeting the apicoplast in malaria." Biochemical Society Transactions 47, no. 4 (August 5, 2019): 973–83. http://dx.doi.org/10.1042/bst20170563.
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Abstract Malaria continues to be one of the leading causes of human mortality in the world, and the therapies available are insufficient for eradication. Severe malaria is caused by the apicomplexan parasite Plasmodium falciparum. Apicomplexan parasites, including the Plasmodium spp., are descendants of photosynthetic algae, and therefore they possess an essential plastid organelle, named the apicoplast. Since humans and animals have no plastids, the apicoplast is an attractive target for drug development. Indeed, after its discovery, the apicoplast was found to host the target pathways of some known antimalarial drugs, which motivated efforts for further research into its biological functions and biogenesis. Initially, many apicoplast inhibitions were found to result in ‘delayed death’, whereby parasite killing is seen only at the end of one invasion-egress cycle. This slow action is not in line with the current standard for antimalarials, which seeded scepticism about the potential of compounds targeting apicoplast functions as good candidates for drug development. Intriguingly, recent evidence of apicoplast inhibitors causing rapid killing could put this organelle back in the spotlight. We provide an overview of drugs known to inhibit apicoplast pathways, alongside recent findings in apicoplast biology that may provide new avenues for drug development.
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Kugasia, Irfanali R., Farhana K. Polara, and Hussein Assallum. "Recrudescence ofPlasmodium malariaeafter Quinine." Case Reports in Medicine 2014 (2014): 1–3. http://dx.doi.org/10.1155/2014/590265.
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Plasmodium malariaecauses uncommon benign malaria found in the malaria endemic regions mostly of Sub-Saharan Africa. AsPlasmodium malariaedoes not have a continued liver stage in humans the only way to have reinfection without reexposure is through recrudescence. However, reports of its recrudescence after antimalarials are rare with only a handful of case reports in the literature. Research in this field to date has not been able to establish definitively an emergence of resistance inPlasmodium malariaeto commonly used antimalarials. In the presented case, patient had a recrudescence ofP. malariaeafter full treatment with quinine and clindamycin. This recrudescence was treated with full course of chloroquine with clearance of parasite from blood immediately after treatment and at two months’ follow up. The recrudescence in this case cannot be explained by mechanisms explained in prior articles. We propose that the indolence of some of thePlasmodium malariaetrophozoites in the blood can shield them from the effect of the toxic effects of antimalarials and enable them to produce recrudescence later. However, when recrudescence happens, this should not be considered a case of development of resistance and a course of chloroquine should be considered.
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Larco Rojas, X. E., A. Crespo Golmar, C. Moriano, A. López Robles, E. Diez Alvarez, and T. Pérez Sandoval. "SAT0180 ANTIMALARIAL DRUGS ASSOCIATED RETINOPATHY IN SYSTEMIC LUPUS ERYTHEMATOSUS." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1031.3–1031. http://dx.doi.org/10.1136/annrheumdis-2020-eular.5996.
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Background:The antimalarials remain to be the main treatment for Systemic Lupus Erythematosus (SLE). Its most important limitation when you want to increase dose or remain using them is the occurrence of retinal toxicity, which appears in a small number of patients. Since the lesions can progress even with drug withdrawal is important to perform a screening for an early diagnosis.Objectives:To describe ocular toxicity in patients with SLE treated with antimalarials that attended the rheumatology office and to identify possible associated risk factors.Methods:We performed a cross-sectional, retrospective study of SLE patients diagnosed of antimalarial drugs associated retinopathy, that were included in the data base of the Rheumatology department in León`s Hospital between 2014-2019. Multiple clinical and therapeutic factors potentially associated with retinal toxicity were analyzed including: age, chronic kidney disease (CKD), liver failure, smoking, hypertension, Diabetes mellitus, presence of previous retinopathy, type of treatment, duration, daily dose and cumulative dose and tamoxifen intake. The diagnosis of retinopathy was performed by the Ophthalmology department. The dose of hydroxychloroquine (HCQ) used was of 400mg/day and chloroquine (CQ) 250mg/day.Results:437 medical records were analyzed, 20 patients diagnosed of antimalarial retinopathy were included (4,57%), 90% of them were women. The age of diagnosis was more than 40 years in 18 patients (90%) and more than 60 years in 10 (50%) with a median of 60 years (IQR: 32,25).The duration of treatment was ≤ 5 years in 10 patients (50%), between 6-10 years in 6 (30%), between 11-15 years in 2(10%) and between 16-20 years in 2 (10%) with a median of exposure of 5,5 years (IQR: 6,5); 15 patients (75%) were in treatment with HCQ, with CQ 2 patients (10%) and with both of them sequentially 3 patients (15%).Of the group of patients treated with HCQ 35 % were above the global accumulated recommended dose (1000 g) and 71% of them were on treatment more than 10 years. In the group treated with CQ none were above the global recommended dose (460g). Of the 3 patients that took both drugs, two were above the recommended dose for HCQ.25% of the patients had CKD and 10% liver failure, 20% of the patients were active smokers and 15% ex-smokers.10% of the sample had previous retinopathy related with other comorbidities (age related retinopathy and diabetes), associating hypertension and diabetes mellitus in the same percentage (15%).Severe retinopathy was found in 1 patient (5%), mild-moderate in 9 patients (45%), retinopathy stages were not specified in 10 patients (50%).Conclusion:In our sample we observed a prevalence of antimalarials retinopathy of 4,57%, similar of what is found in the literature. Half of the patients had retinopathy in a period of treatment ≤ 5 years, being a described risk factor the duration of treatment of more than 6 years. This early manifestation could be related to the presence of other comorbidities like hypertension, diabetes and CKD.Dose readjustment should be considered in patients with a period of treatment of more than 10 years. Age seems to be an associated factor for the development of antimalarials retinopathy and to perform a screening in the first year of treatment is important to rule out basal disease related with more risk to develop ocular toxicity.References:[1]Jorge, A., Ung, C., Young, L.H. et al. Hydroxychloroquine retinopathy — implications of research advances for rheumatology care. Nat Rev Rheumatol 14, 693–703 (2018).[2]Mukwikwi ER, Pineau CA, Vinet E. et al. Retinal Complications in Systemic Lupus Erythematosus Patients Treated with Antimalarial Drugs. J Rheumatol. 2019 Sep 1. jrheum.181102[3]Abdulaziz N, Shah AR, McCune WJ. Hydroxychloroquine: balancing the need to maintain therapeutic levels with ocular safety: an update. Curr Opin Rheumatol. 2018 May;30(3):249-255.Disclosure of Interests:None declared
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Okolo, CE, LK Eban, LU Amazu, LC Chukwu, SC Ohadoma, and FN Osuala. "In-vitro anti-malarial activity of Chikadoma plant from the rainforest of Southern Nigeria." Journal of Drug Delivery and Therapeutics 10, no. 5 (September 15, 2020): 251–54. http://dx.doi.org/10.22270/jddt.v10i5.4322.
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Background: Malaria remains a life-threatening tropical disease. Due to the development of resistance to the commonly available orthodox antimalarials which of course, poses a great challenge in malaria-controlling-program, alternative and complementary approach becomes imperative thereby making phytotherapy a research focus. Objectives: To investigate the effect of chikadoma plant using its methanol leaf extract against a plasmodium-mediated tropical disease, malaria. Materials and Methods: The culture samples of Plasmodium (P.) falciparum from 20 symptomatic adult outpatients were used in the antimalarial in-vitro test. For cultivation of P. falciparum, the culture medium employed was Roswell Park Memorial Institute (RPMI) 1640. Optical microscopy was used for parasite quantification in the performance of antiplasmodial in-vitro assays. The leaf extract of chikadoma dissolved in dimethylsulphoxide (DMSO) was the treatment, prepared into 7 different levels of concentration (3.125, 6.25, 12.5, 25, 50, 100, and 200 mg/mL) while culture medium with the malarial parasite alone served as negative control. Micromalarial culture preceded by culture synchronized with sorbitol 5%, were divided into “control” and “treated groups”, followed by incubation in CO2 candle jar at 370C for 72 h. The percentage of parasitemia was measured 8 h, showing the activity of the extract on P. falciparum stages of proliferation. Thin blood smear from the erythrocytes layer was made and stained with 10% Giemsa for 30 mins to estimate the parasitemia. The antimalarial activity of the extract was calculated using Probit analysis by counting the 50% growth inhibition (IC50). Results: The growth of P. falciparum was inhibited by the extract on mature schizont stage; and the IC50 of the extract after 40 h incubation was 3.0 mg/mL. Conclusion: The leaf extract of chikadoma significantly has antimalarial effect in-vitro against P. falciparum.
Keywords: Chikadoma; Lupinus arboreus; antimalarial activity; tropical disease; Nigeria.
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Hammam, Elie, Guruprasad Ananda, Ameya Sinha, Christine Scheidig-Benatar, Mylene Bohec, Peter R. Preiser, Peter C. Dedon, Artur Scherf, and Shruthi S. Vembar. "Discovery of a new predominant cytosine DNA modification that is linked to gene expression in malaria parasites." Nucleic Acids Research 48, no. 1 (November 28, 2019): 184–99. http://dx.doi.org/10.1093/nar/gkz1093.
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Abstract DNA cytosine modifications are key epigenetic regulators of cellular processes in mammalian cells, with their misregulation leading to varied disease states. In the human malaria parasite Plasmodium falciparum, a unicellular eukaryotic pathogen, little is known about the predominant cytosine modifications, cytosine methylation (5mC) and hydroxymethylation (5hmC). Here, we report the first identification of a hydroxymethylcytosine-like (5hmC-like) modification in P. falciparum asexual blood stages using a suite of biochemical methods. In contrast to mammalian cells, we report 5hmC-like levels in the P. falciparum genome of 0.2–0.4%, which are significantly higher than the methylated cytosine (mC) levels of 0.01–0.05%. Immunoprecipitation of hydroxymethylated DNA followed by next generation sequencing (hmeDIP-seq) revealed that 5hmC-like modifications are enriched in gene bodies with minimal dynamic changes during asexual development. Moreover, levels of the 5hmC-like base in gene bodies positively correlated to transcript levels, with more than 2000 genes stably marked with this modification throughout asexual development. Our work highlights the existence of a new predominant cytosine DNA modification pathway in P. falciparum and opens up exciting avenues for gene regulation research and the development of antimalarials.
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Guggisberg, Ann M., Rachel E. Amthor, and Audrey R. Odom. "Isoprenoid Biosynthesis in Plasmodium falciparum." Eukaryotic Cell 13, no. 11 (September 12, 2014): 1348–59. http://dx.doi.org/10.1128/ec.00160-14.
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ABSTRACTMalaria kills nearly 1 million people each year, and the protozoan parasitePlasmodium falciparumhas become increasingly resistant to current therapies. Isoprenoid synthesis via the methylerythritol phosphate (MEP) pathway represents an attractive target for the development of new antimalarials. The phosphonic acid antibiotic fosmidomycin is a specific inhibitor of isoprenoid synthesis and has been a helpful tool to outline the essential functions of isoprenoid biosynthesis inP. falciparum. Isoprenoids are a large, diverse class of hydrocarbons that function in a variety of essential cellular processes in eukaryotes. InP. falciparum, isoprenoids are used for tRNA isopentenylation and protein prenylation, as well as the synthesis of vitamin E, carotenoids, ubiquinone, and dolichols. Recently, isoprenoid synthesis inP. falciparumhas been shown to be regulated by a sugar phosphatase. We outline what is known about isoprenoid function and the regulation of isoprenoid synthesis inP. falciparum, in order to identify valuable directions for future research.
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Thiengsusuk, Artitaya, Phunuch Muhamad, Wanna Chaijaroenkul, and Kesara Na-Bangchang. "Antimalarial Activity of Piperine." Journal of Tropical Medicine 2018 (December 6, 2018): 1–7. http://dx.doi.org/10.1155/2018/9486905.
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Malaria remains a public health problem in tropical and subtropical regions. Resistance of Plasmodium falciparum to artemisinins in Southeast Asia is a great concern for disease control and research on discovery and development of new alternative antimalarial drugs is urgently required. In a previous study, the fruit of Piper chaba Hunt. was demonstrated to exhibit promising antimalarial activity against the asexual stage of 3D7 (chloroquine-sensitive) and K1 (chloroquine-resistant) P. falciparum clones. The aim of the present study was to further investigate the antimalarial activity of piperine, the major isolated constituent of Piper chaba Hunt. fruits against both P. falciparum clones. The antimalarial activity was determined using SYBR green-I-based assay and morphological change was observed under the light microscope with Giemsa staining. The median IC50 (concentration that inhibits parasite growth by 50%) values of piperine against 3D7 and K1 P. falciparum were 111.5 and 59 μM, respectively. A marked change in parasite morphology was observed within 48 hours of piperine exposure. Results of real-time PCR showed no effect of piperine on modulating the expression of the three genes associated with antimalarial drug resistance in P. falciparum, i.e., pfcrt, pfmdr1, and pfmrp1. Piperine could be a promising candidate for further development as an antimalarial drug based on its antimalarial potency and low risk of resistance development.
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Okombo, John, and Kelly Chibale. "Recent updates in the discovery and development of novel antimalarial drug candidates." MedChemComm 9, no. 3 (2018): 437–53. http://dx.doi.org/10.1039/c7md00637c.
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Concerns of emerging resistance and the search for molecules with potential for single exposure radical cure and prophylaxis have spurred research into compounds with target profiles for clinical development into antimalarial drugs.
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Tiwari, Mohit K., Dharmendra K. Yadav, and Sandeep Chaudhary. "Recent Developments in Natural Product Inspired Synthetic 1,2,4- Trioxolanes (Ozonides): An Unusual Entry into Antimalarial Chemotherapy." Current Topics in Medicinal Chemistry 19, no. 10 (July 19, 2019): 831–46. http://dx.doi.org/10.2174/1568026619666190412104042.
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According to WHO “World health statistics 2018”, malaria alongside acute respiratory infections and diarrhoea, is one of the major infectious disease causing children’s death in between the age of 1-5 years. Similarly, according to another report (2016) malaria accounts for approximately 3.14% of the total disease burden worldwide. Although malaria has been widely eradicated in many parts of the world, the global number of cases continues to rise due to the rapid spread of malaria parasites that are resistant to antimalarial drugs. Artemisinin (8), a major breakthrough in the antimalarial chemotherapy was isolated from the plant Artemisia annua in 1972. Its semi-synthetic derivatives such as artemether (9), arteether (10), and artesunic acid (11) are quite effective against multi-drug resistant malaria strains and are currently the drug of choice for the treatment of malaria. Inspite of exhibiting excellent antimalarial activity by artemisinin (8) and its derivatives, parallel programmes for the discovery of novel natural and synthetic peroxides were also the area of investigation of medicinal chemists all over the world. In these continuous efforts of extensive research, natural ozonide (1,2,4- trioxolane) was isolated from Adiantum monochlamys (Pteridaceae) and Oleandra wallichii (Davalliaceae) in 1976. These naturally occurring stable ozonides inspired chemists to investigate this novel class for antimalarial chemotherapy. The first identification of unusually stable synthetic antimalarial 1,2,4-trioxolanes was reported in 1992. Thus, an unusual entry of ozonides in the field of antimalarial chemotherapy had occurred in the early nineties. This review highlights the recent advancements and historical developments observed during the past 42 years (1976-2018) focusing mainly on important ventures of the antimalarial 1,2,4-trioxolanes (ozonides).
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Moelyadi, Felly, Prawesty Diah Utami, and Irmawati M. Dikman. "Inhibitory Effect of Active Substances of Lollyfish (Holothuria atra) Against the Development of Plasmodium falciparum Based on In Silico Study." ILMU KELAUTAN: Indonesian Journal of Marine Sciences 25, no. 4 (October 7, 2020): 135–42. http://dx.doi.org/10.14710/ik.ijms.25.4.135-142.
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The high level of artemisinin resistance as the antimalarial drug makes the active substances found of lollyfish (Holothuria atra) become a very useful discovery as a new antimalarial drug. The purpose of this research is to find out the inhibitory effect of the active substances of lollyfish against the development of Plasmodium falciparum with in silico method. This is a one-shot experimental study research. Based on the test of potentially active substances of lollyfish through PubChem (https://pubchem.ncbi.nlm.nih.gov/), there are pyrogallol and catechin that have potential as the antimalarial drug. Pyrogallol, chlorogenic acid, catechin dan ascorbic acid have indirect inhibition to P. falciparum Orotidine 5-Monophosphate Decarboxylase (PfOMPDC) through carbon dioxide (CO2) and it is visualized by STITCH DB Version 5.0 (http://stitch.embl.de/). The binding affinity score of catechin, obtained from molecular docking, is higher than other substances and artemisinin. The Physicochemical and pharmacokinetic activity of the substance was predicted through SWISS ADME (http://www.swissadme.ch/index.php), while the toxicity was predicted through Pro-Tox (http://tox.charite.de/protox_II/). Catechin is a substance in lollyfish that is the safest because its lowest toxicity and very effective to be used as the antimalarial drug because of its high lethal dose 50 (LD50). Therefore, active substances in lollyfish have inhibitory effects against the development of P. falciparum based on in silico study.
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Oliveira, Alaíde B., Maria Fâni Dolabela, Fernão C. Braga, Rose L. R. P. Jácome, Fernando P. Varotti, and Marinete M. Póvoa. "Plant-derived antimalarial agents: new leads and efficient phythomedicines. Part I. Alkaloids." Anais da Academia Brasileira de Ciências 81, no. 4 (December 2009): 715–40. http://dx.doi.org/10.1590/s0001-37652009000400011.
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Malaria remains one of the most serious world health problem and the major cause of mortality and morbidity in the endemic regions. Brazil is among the 30 high-burden countries and most of the cases occur in the Legal Amazonian Region. New chemotherapeutical agents are needed for the treatment of malaria. Many plant species are used in traditional medicines of malarious countries and a relatively few number of these have been investigated for evaluation of their antimalarial effect. Still lower is the number of those that have had the active natural compounds isolated and the toxicity determined. This area is, then, of great research interest. discovery project of antimalarial natural products from plants traditionally used to treat malaria must include in vitro and in vivo assays as well as bioguided isolation of active compounds. The final products would be antimalarial chemical entities, potential new drugs or templates for new drugs development, and/or standardized antimalarial extracts which are required for pre-clinical and clinical studies when the aim is the development of effective and safe phythomedicines. This review discusses these two approaches, presents briefly the screening methodologies for evaluation of antimalarial activity and focuses the activity of alkaloids belonging to different structural classes as well as its importance as new antimalarial drugs or leads and chemical markers for phytomedicines.
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Flotow, Horst, Chung-Yan Leong, and Antony D. Buss. "Development of a Plasmepsin II Fluorescence Polarization Assay Suitable for High Throughput Antimalarial Drug Discovery." Journal of Biomolecular Screening 7, no. 4 (August 2002): 367–71. http://dx.doi.org/10.1177/108705710200700409.
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Despite decades of research, malaria remains the world's most deadly parasitic disease. New treatments with novel mechanisms of action are urgently needed. Plasmepsin II is an aspartyl protease that has been validated as an antimalarial therapeutic target enzyme. Although natural products form the basis of most modern antimalarial drugs, no systematic high-throughput screening has been reported against this target. We have designed an effective strategy for carrying out high-throughput screening of an extensive library of natural products that uses a fluorescence resonance energy transfer primary screening assay in tandem with a fluorescence polarization assay. This strategy allows rapid screening of the library coupled with effective discrimination and elimination of false-positive samples and selection of true hits for chemical isolation of inhibitors of plasmepsin II.
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Amelo, Wote, and Eyasu Makonnen. "Efforts Made to Eliminate Drug-Resistant Malaria and Its Challenges." BioMed Research International 2021 (August 30, 2021): 1–12. http://dx.doi.org/10.1155/2021/5539544.
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Since 2000, a good deal of progress has been made in malaria control. However, there is still an unacceptably high burden of the disease and numerous challenges limiting advancement towards its elimination and ultimate eradication. Among the challenges is the antimalarial drug resistance, which has been documented for almost all antimalarial drugs in current use. As a result, the malaria research community is working on the modification of existing treatments as well as the discovery and development of new drugs to counter the resistance challenges. To this effect, many products are in the pipeline and expected to be marketed soon. In addition to drug and vaccine development, mass drug administration (MDA) is under scientific scrutiny as an important strategy for effective utilization of the developed products. This review discusses the challenges related to malaria elimination, ongoing approaches to tackle the impact of drug-resistant malaria, and upcoming antimalarial drugs.
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Mylne, Joshua S., and Keith A. Stubbs. "Antimalarial Drugs as Inspiration for Herbicides." Outlooks on Pest Management 31, no. 5 (October 1, 2020): 216–20. http://dx.doi.org/10.1564/v31_oct_05.
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In addition to good stewardship, the unabated rise in herbicide resistance and dearth of truly new herbicides demands that new molecules be found. Over 30 years ago, a chloroplast-like organelle was found in the malarial parasite Plasmodium falciparum and herbicides demonstrated a close relationship existed to plants. Recently this idea was turned on its head by exploiting the boom in malaria research to search for new herbicide chemistry and it provided interesting starting points for development. The merit of such an approach is underlined by tetflupyrolimet, the first truly novel herbicide in 30 years, and whose target has been a popular subject for antimalarial drug development for 15 years. Which other antimalarial targets, drugs and drug leads might reach across the parasite-plant divide to inspire new herbicides?
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Uzor, Philip F. "Alkaloids from Plants with Antimalarial Activity: A Review of Recent Studies." Evidence-Based Complementary and Alternative Medicine 2020 (February 12, 2020): 1–17. http://dx.doi.org/10.1155/2020/8749083.
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Malaria is one of the major health problems in developing countries. The disease kills a large number of people every year and also affects financial status of many countries. Resistance of the plasmodium parasite, the causative agent, to the existing drugs, including chloroquine, mefloquine, and artemisinin based combination therapy (ACT), is a serious global issue in malaria treatment and control. This warrants an urgent quest for novel compounds, particularly from natural sources such as medicinal plants. Alkaloids have over the years been recognized as important phytoconstituents with interesting biological properties. In fact, the first successful antimalarial drug was quinine, an alkaloid, which was extracted from Cinchona tree. In the present review work, the alkaloids isolated and reported recently (2013 till 2019) to possess antimalarial activity are presented. Several classes of alkaloids, including terpenoidal, indole, bisindole, quinolone, and isoquinoline alkaloids, were identified with a promising antimalarial activity. It is hoped that the reports of the review work will spur further research into the structural modification and/or development of the interesting compounds as novel antimalarial drugs.
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Djimde, Abdoulaye, Martin P. Grobusch, Rella Zoleko Manego, Ghyslain Mombo-Ngoma, Stephane Picot, Issaka Sagara, Colin Sutherland, et al. "OC 8721 WANECAM II – A CLINICAL TRIAL PROGRAMME TO ASSESS SAFETY, EFFICACY AND TRANSMISSION-BLOCKING PROPERTIES OF A NEW ANTIMALARIAL KAF156 (GANAPLACIDE) IN UNCOMPLICATED MALARIA IN WEST AND CENTRAL AFRICA." BMJ Global Health 4, Suppl 3 (April 2019): A17.3—A18. http://dx.doi.org/10.1136/bmjgh-2019-edc.43.
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BackgroundDespite major progress in the past decade, malaria remains a major public health problem in sub-Saharan Africa. West and Central Africa account for nearly 2/3 of the burden currently attributable to falciparum malaria. Artemisinin-based combination therapies (ACT) are a cornerstone of our strategy for controlling and eventually eliminating malaria. However, reduced responsiveness/resistance to artemisinin derivatives and to ACTs, an increasing problem in South-East Asia is a major concern. It is of utmost importance to develop new antimalarial drugs from novel chemical classes that can replace ACTs. KAF156, an imidazolepiperazine, is a leading candidate in the antimalarial drug development pipeline. Combination of KAF156 with a Solid Dispersion Formulation of lumefantrine (LUM-SDF) is expected to be fast acting, fully curative, improve patient adherence and can potentially reduce malaria transmission.MethodsWANECAM II proposes to advance the clinical development of KAF156 through clinical trials in adults and children, with integrated capacity building and infrastructure development activities. The trial programme will be undertaken in the context of networking, team-building, leadership development and community engagement schemes that will involve intra-European, European-African and intra-African collaborative activities. WANECAM II will accelerate the clinical study of children less than 2 years of age which are the key target for new antimalarial treatments.ResultsBy the end of the project, the results are expected to contribute to the registration of KAF156/LUM-SDF through stringent regulatory health authorities, increase biomedical research capacity in the consortium and effectively promote networking among the respective teams. A new clinical research team in Niger, a grossly underrepresented country in the African research landscape, will be developed and further increase capacity and infrastructure in the consortium.ConclusionProviding a new antimalarial drug combination that does not contain an artemisinin derivative and is effective against resistant P. falciparum strains as well as gametocytes and that is likely to be taken in 3 or fewer single doses will be a major advance in the field. The new combination of KAF156 with LUM-SDF is expected to provide such major advance upon successful conclusion of the WANECAM II project.
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Mbaba, Mziyanda, Taryn M. Golding, and Gregory S. Smith. "Recent Advances in the Biological Investigation of Organometallic Platinum-Group Metal (Ir, Ru, Rh, Os, Pd, Pt) Complexes as Antimalarial Agents." Molecules 25, no. 22 (November 12, 2020): 5276. http://dx.doi.org/10.3390/molecules25225276.
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In the face of the recent pandemic and emergence of infectious diseases of viral origin, research on parasitic diseases such as malaria continues to remain critical and innovative methods are required to target the rising widespread resistance that renders conventional therapies unusable. The prolific use of auxiliary metallo-fragments has augmented the search for novel drug regimens in an attempt to combat rising resistance. The development of organometallic compounds (those containing metal-carbon bonds) as antimalarial drugs has been exemplified by the clinical development of ferroquine in the nascent field of Bioorganometallic Chemistry. With their inherent physicochemical properties, organometallic complexes can modulate the discipline of chemical biology by proffering different modes of action and targeting various enzymes. With the beneficiation of platinum group metals (PGMs) in mind, this review aims to describe recent studies on the antimalarial activity of PGM-based organometallic complexes. This review does not provide an exhaustive coverage of the literature but focusses on recent advances of bioorganometallic antimalarial drug leads, including a brief mention of recent trends comprising interactions with biomolecules such as heme and intracellular catalysis. This resource can be used in parallel with complementary reviews on metal-based complexes tested against malaria.
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Na-Bangchang, Kesara, and Juntra Karbwang. "Current status of malaria chemotherapy and the role of pharmacology in antimalarial drug research and development." Fundamental & Clinical Pharmacology 23, no. 4 (August 2009): 387–409. http://dx.doi.org/10.1111/j.1472-8206.2009.00709.x.
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Nandal, Rimmy, Aakash Deep, Ishwar Singh, Meenakshi Kaushik, Hoti S. L., Balasubramanian Narasimhan, Rakesh K. Marwaha, and Arun K. Sharma. "Synthesis of Metal Complexes of Primaquine and In-vitro Antimalarial Evaluation Against Plasmodium falciparum." Current Bioactive Compounds 15, no. 6 (January 23, 2020): 631–36. http://dx.doi.org/10.2174/1573407214666180720124844.
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Background: Resistance to malarial drugs represents a major obstacle in the treatment of disease, thereby increasing the need for more efficient drugs. The development of metal complexes offers the medicinal chemist an opportunity to expand the activity of drugs. For providing supportive therapy to the host to boost its immune system several new antimalarial drugs are being beneath research, but sufficient information on their efficacy is yet not available. Methods: In view of above, eight drug metal complexes (Ba (II), Ca (II), Zn (II), St (II), Hg (II), Fe (III), Cu (II), Ni (II) of Sulfamethoxazole (SMX) and Primaquine were synthesized and in-vitro evaluated for their antimalarial activity against malaria parasite Plasmodium falciparum by using fluorescence based assay. Result: The antimalarial activity of Nickel (EC50= 1.41µM) and Zinc (EC50=0.96µM) complexes have shown tremendous activity as compared to the standard drug Primaquine (EC50=0.07µM). The structures of all these newly synthesized derivatives were confirmed by spectral data (IR, 1H NMR, 13C NMR and Mass spectrometry). Conclusion: In conclusion, this study describes that the preparation and antimalarial evaluation of metal complexes of primaquine and sulphamethoxazole. Evaluation of their possible biological activities such as antimalarial activity was carried out and most of the synthesized compounds (Nickel and Zinc metal complexes) showed the good activity as compared to the standard drug primaquine. Therefore the compounds are appropriate candidates for more investigation and some more derivatives can be synthesized to get an imminent into the structure activity relationship of these compounds to be employed as biologically useful agents.
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She, Rui, Yangmu Huang, Tingting Xu, and Yan Guo. "Challenges of research and development on antimalarial medicinal products in China: a bibliometric analysis and systematic review." Transactions of The Royal Society of Tropical Medicine and Hygiene 110, no. 11 (November 2016): 649–56. http://dx.doi.org/10.1093/trstmh/trw083.
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Sanz, Laura M., M. Belen Jiménez-Díaz, Benigno Crespo, Cristina De-Cozar, M. Jesus Almela, Iñigo Angulo-Barturen, Pablo Castañeda, et al. "Cyclopropyl Carboxamides, a Chemically Novel Class of Antimalarial Agents Identified in a Phenotypic Screen." Antimicrobial Agents and Chemotherapy 55, no. 12 (October 3, 2011): 5740–45. http://dx.doi.org/10.1128/aac.05188-11.
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ABSTRACTMalaria is one of the deadliest infectious diseases in the world, with the eukaryotic parasitePlasmodium falciparumcausing the most severe form of the disease. Discovery of new classes of antimalarial drugs has become an urgent task to counteract the increasing problem of drug resistance. Screening directly for compounds able to inhibit parasite growthinvitrois one of the main approaches the malaria research community is now pursuing for the identification of novel antimalarial drug leads. Very recently, thousands of compounds with potent activity against the parasiteP. falciparumhave been identified and information about their molecular descriptors, antiplasmodial potency, and cytotoxicity is publicly available. Now the challenges are how to identify the most promising chemotypes for further development and how best to progress these compounds through a lead optimization program to generate antimalarial drug candidates. We report here the first chemical series to be characterized from one of those screenings, a completely novel chemical class with the generic name cyclopropyl carboxamides that has never before been described as having antimalarial or other pharmacological activities. Cyclopropyl carboxamides are potent inhibitors of drug-sensitive and -resistant strains ofP. falciparuminvitroand showinvivooral efficacy in malaria mouse models. In the present work, we describe the biological characterization of this chemical family, showing that inhibition of their still unknown target has very favorable pharmacological consequences but the compounds themselves seem to select for resistance at a high frequency.
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Pannu, Ashok K. "Malaria today: advances in management and control." Tropical Doctor 49, no. 3 (May 6, 2019): 160–64. http://dx.doi.org/10.1177/0049475519846382.
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Over the past two decades, malaria-related deaths have reduced substantially, especially in African children. However, the global malaria burden still remains high. The recent emergence of resistance to artemisinin, the backbone of malaria management, could threaten malaria control. Importantly, over the past five years, there has been an upsurge in research in the development of novel antimalarial drugs (and combinations), malaria vaccine and new vector-control strategies that can boost the malaria control programme.
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Bialik, Maria, Marzena Kuras, Marcin Sobczak, and Ewa Oledzka. "Achievements in Thermosensitive Gelling Systems for Rectal Administration." International Journal of Molecular Sciences 22, no. 11 (May 23, 2021): 5500. http://dx.doi.org/10.3390/ijms22115500.
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Rectal drug delivery is an effective alternative to oral and parenteral treatments. This route allows for both local and systemic drug therapy. Traditional rectal dosage formulations have historically been used for localised treatments, including laxatives, hemorrhoid therapy and antipyretics. However, this form of drug dosage often feels alien and uncomfortable to a patient, encouraging refusal. The limitations of conventional solid suppositories can be overcome by creating a thermosensitive liquid suppository. Unfortunately, there are currently only a few studies describing their use in therapy. However, recent trends indicate an increase in the development of this modern therapeutic system. This review introduces a novel rectal drug delivery system with the goal of summarising recent developments in thermosensitive liquid suppositories for analgesic, anticancer, antiemetic, antihypertensive, psychiatric, antiallergic, anaesthetic, antimalarial drugs and insulin. The report also presents the impact of various types of components and their concentration on the properties of this rectal dosage form. Further research into such formulations is certainly needed in order to meet the high demand for modern, efficient rectal gelling systems. Continued research and development in this field would undoubtedly further reveal the hidden potential of rectal drug delivery systems.
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Pamudi, Berwi Fazri, Azizahwati Azizahwati, and Arry Yanuar. "IN-SILICO SCREENING AGAINST ANTIMALARIAL TARGET PLASMODIUM FALCIPARUM ENOYL-ACYL CARRIER PROTEIN REDUCTASE." Asian Journal of Pharmaceutical and Clinical Research 10, no. 17 (October 1, 2017): 127. http://dx.doi.org/10.22159/ajpcr.2017.v10s5.23114.
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Objective: Malaria is a parasitic infection that causes worldwide health problems. The absence of an effective vaccine and Plasmodium strains that are resistant to antimalarial drugs emphasize the importance of developing new chemotherapeutic agents. The use of computers for in-silico screening, or virtual screening, is currently being developed as a method for discovering antimalarial drugs. One of the enzymes that can support the development of the malaria parasite is the Plasmodium falciparum enoyl-acyl carrier protein reductase (PfENR). Inhibition of these enzymes leads to Type II lipid biosynthesis inhibition on the parasite.Methods: This research investigates the use of virtual screening to find PfENR inhibitor candidates. A molecular docking method using GOLD software and the medicinal plants in Indonesia database will be used. This target has been optimized by the removal of residues and the addition of charge. Ligand is expected to be an inhibitor of PfENR.Results: In-silico screening, or virtual screening, found that the top five compounds with the highest GOLD score at trial are kaempferol 3-rhamnosyl- (1-3)-rhamnosyl-(1-6)-glucoside; cyanidin 3,5-di-(6-malonylglucoside); 8-hydroxyapigenin 8-(2’’, 4’’-disulfato glucuronide); epigallocatechin 3,5,-di- O-gallat; quercetin 3,4’-dimethyl ether 7-alpha-L-arabinofuranosyl-(1-6)-glucoside. They had GOLD scores of 94.73, 95.90, 86.46, 85.39, and 84.40, respectively.Conclusions: There are two candidate inhibitor compounds from tea (Camellia sinensis), which have potential for development as an antimalarial drug, which are kaempferol 3-rhamnosyl-(1-3)-rhamnosyl-(1-6)-glucoside and epigallocatechin 3,5,-di-O-gallate, with a GOLD score of 94.73 and 85.39, respectively.
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Yadav, Brijesh S., Navaneet Chaturvedi, and Ninoslav Marina. "Recent Advances in System Based Study for Anti-Malarial Drug Development Process." Current Pharmaceutical Design 25, no. 31 (November 14, 2019): 3367–77. http://dx.doi.org/10.2174/1381612825666190902162105.
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Background: Presently, malaria is one of the most prevalent and deadly infectious disease across Africa, Asia, and America that has now started to spread in Europe. Despite large research being carried out in the field, still, there is a lack of efficient anti-malarial therapeutics. In this paper, we highlight the increasing efforts that are urgently needed towards the development and discovery of potential antimalarial drugs, which must be safe and affordable. The new drugs thus mentioned are also able to counter the spread of malaria parasites that have been resistant to the existing agents. Objective: The main objective of the review is to highlight the recent development in the use of system biologybased approaches towards the design and discovery of novel anti-malarial inhibitors. Method: A huge literature survey was performed to gain advance knowledge about the global persistence of malaria, its available treatment and shortcomings of the available inhibitors. Literature search and depth analysis were also done to gain insight into the use of system biology in drug discovery and how this approach could be utilized towards the development of the novel anti-malarial drug. Results: The system-based analysis has made easy to understand large scale sequencing data, find candidate genes expression during malaria disease progression further design of drug molecules those are complementary of the target proteins in term of shape and configuration. Conclusion: The review article focused on the recent computational advances in new generation sequencing, molecular modeling, and docking related to malaria disease and utilization of the modern system and network biology approach to antimalarial potential drug discovery and development.
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Thakral, Samridhi, and Vikramjeet Singh. "Recent Development on Importance of Heterocyclic Amides as Potential Bioactive Molecules: A Review." Current Bioactive Compounds 15, no. 3 (May 7, 2019): 316–36. http://dx.doi.org/10.2174/1573407214666180614121140.
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Background: Heterocyclic compounds are an integral part of the chemical and life sciences and constitute a considerable quantum of the modern research that is being currently pursued throughout the world. Methods: This review was prepared by collecting the available literature reports on various databases and an extract was prepared for each report after thorough study and compiling the recent literature reports on heterocyclic amides from 2007 to 2018. Results: This review summarizes the bio-potential of heterocyclic amides as antimicrobial, anticancer, anti-tubercular and antimalarial agents which would be very promising in the field of medicinal chemistry. Conclusion: A wide variety of heterocyclic amides have already been reported and some are currently being used as active medicaments for the treatment of disease. Still, the research groups are focusing on the development of newer heterocyclic amide derivatives with better efficacy, potency and lesser side effects. This area has got the tremendous potential to come up with new chemical entities of medicinal importance.
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de Souza Barbosa, Camila, Daniel Silqueira Martins Guimarães, Juliana da Costa Alves, Cristiana Ferreira Alves de Brito, Renato Márcio Ribeiro-Viana, Fernando de Pilla Varotti, and Gustavo Henrique Ribeiro Viana. "Halogenation as a Strategy to Improve Antiplasmodial Activity: A Report of New 3-Alkylpyridine Marine Alkaloid Analogs." International Journal of Travel Medicine and Global Health 7, no. 4 (December 15, 2019): 129–34. http://dx.doi.org/10.15171/ijtmgh.2019.27.
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Introduction: Due to the emergence of resistance to antimalarial drugs as well as the lack of vaccination for malaria, there is an urgent demand for the development of new antimalarial alternatives. Recently, our research group developed a new set of 3-alkylpyridine marine alkaloid analogs, of which a compound known as compound 5 was found to be inactive against Plasmodium falciparum.Methods: Herein, we report a successful halogenation strategy to improve the antiplasmodial activity of compound 5 through the replacement of a hydroxyl group by chlorine (compound 6) and fluorine (compound 7) atoms. Results: Compounds 6 and 7 showed improved antiplasmodial activities (IC50 = 7.2 and 8.3 µM, respectively) 20 times higher than that of their precursor, compound 5 (IC50 = 210.7 µM). Ultraviolet-visible titration experiments demonstrated that halogenation of compound 5 did not alter its ability to bind its target, hematin. Conclusion: Halogenation can enhance the antiplasmodial activity of a compound without altering its mechanism of action.
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Aguiar, Anna Caroline, Lorena R. F. de Sousa, Celia R. S. Garcia, Glaucius Oliva, and Rafael V. C. Guido. "New Molecular Targets and Strategies for Antimalarial Discovery." Current Medicinal Chemistry 26, no. 23 (October 10, 2019): 4380–402. http://dx.doi.org/10.2174/0929867324666170830103003.
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Malaria remains a major health problem, especially because of the emergence of resistant P. falciparum strains to artemisinin derivatives. In this context, safe and affordable antimalarial drugs are desperately needed. New proteins have been investigated as molecular targets for research and development of innovative compounds with welldefined mechanism of action. In this review, we highlight genetically and clinically validated plasmodial proteins as drug targets for the next generation of therapeutics. The enzymes described herein are involved in hemoglobin hydrolysis, the invasion process, elongation factors for protein synthesis, pyrimidine biosynthesis, post-translational modifications such as prenylation, phosphorylation and histone acetylation, generation of ATP in mitochondrial metabolism and aminoacylation of RNAs. Significant advances on proteomics, genetics, structural biology, computational and biophysical methods provided invaluable molecular and structural information about these drug targets. Based on this, several strategies and models have been applied to identify and improve lead compounds. This review presents the recent progresses in the discovery of antimalarial drug candidates, highlighting the approaches, challenges, and perspectives to deliver affordable, safe and low single-dose medicines to treat malaria.
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Chakim, Irfanul, and Tepanata Pumpaibool. "Drug Metabolite as a Novel Tool for Measuring Antimalarial Drug Adherence." Open Public Health Journal 11, no. 1 (June 29, 2018): 288–97. http://dx.doi.org/10.2174/1874944501811010288.
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Malaria has been a major public health problem worldwide. The burden of malaria has been reduced by the adoption of Artemisinin-Combination Therapy (ACT) followed by primaquine dosage in malaria-endemic countries. However, evidences of non-adherence behavior lead to the discovery of antimalarial drug adherence to ensure a successful and satisfactory treatment of ACT, since it is the only available antimalarial drugs against asexual form of the parasite. Unstandardized questionnaires and limited effective alternative approaches have been the major obstacles to measure adherence. With rapid development of pharmacokinetic research, public health researchers can adopt the approach to measure adherence. Notwithstanding, the current structured questionnaire has explained in detail that the measurement and classification of adherence have produced satisfactory results. However, it is subject to social desirability bias. Therefore, in this review, we offer a new strategy combining structured questionnaire and drug metabolite as a novel consensus which eliminates biases. A new classification of adherence and graphical representation of practical strategy and other important factors are provided in this review. Thus, it initiates further works to conduct an intervention program to increase adherence level. Additionally, adherence behavior prevents the development of drug resistance and its spread, increases satisfactory cure rate and inhibits transmission by eliminating gametocyte inside host’s body.
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Muschietti, Liliana V., and Jerónimo L. Ulloa. "Natural Sesquiterpene Lactones as Potential Trypanocidal Therapeutic Agents: A Review." Natural Product Communications 11, no. 10 (October 2016): 1934578X1601101. http://dx.doi.org/10.1177/1934578x1601101036.
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Chagas’ disease and Human African Trypanosomiasis are parasitic diseases that remain major health problems, mainly among the poorest and the most marginalized communities from Latin America and Africa. The scarcity of effective chemotherapy, due to the low investment in the research and development (R&D) of new drugs, together with a high incidence of side effects, and the emergence of drug resistance phenomena emphasize the urgent need for new prophylactic and therapeutic agents. Over the ages, humans have employed natural products to treat a wide spectrum of diseases. Recently, the pharmaceutical industry has focused on plant research and a large body of evidence has been collected to demonstrate the immense potential of medicinal plants as a source of bioactive compounds and lead molecules. In the field of parasitic diseases, drug development from plants has been successful for the sesquiterpene lactone (STL) artemisinin, which is employed as an antimalarial agent. STLs are a large group of naturally occurring terpenoids derived from plants that mostly belong to the Asteraceae family which exhibit a variety of skeletal arrangements and are the largest and most diverse category of natural products with an α-methylene-λ-lactone motif. STLs display a broad spectrum of biological activities such as antitumor, cytotoxic, antibacterial, anthelmintic, uterus contracting, antimalarial, neurotoxic, antiprotozoal and allergic (contact dermatitis) activities. In this context, the purpose of the present review is to provide an overview of the trypanocidal activity reported for STLs against Trypanosoma cruzi and T. brucei rhodesiense over the period 1993–2015.
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Nugraha, Ari S., and Paul A. Keller. "Revealing Indigenous Indonesian Traditional Medicine: Anti-infective Agents." Natural Product Communications 6, no. 12 (December 2011): 1934578X1100601. http://dx.doi.org/10.1177/1934578x1100601240.
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Indonesia is rich in medicinal plants which the population has used traditionally from generation to generation for curing diseases. Our interest in the treatment of infectious diseases has lead to the investigation of traditional Indonesian treatments. In this review, we present a comprehensive review of ethnopharmacologically directed screening in Indonesian medicinal plants to search for new antiviral, antimalarial, antibacterial and antifungal agents. Some potent drug leads have been isolated from Indonesian medicinal plants. Further research is still required for the lead development as well as the search for new bioactive compounds from the enormous medicinal plant resources.
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Verma, Tarawanti, Manish Sinha, and Nitin Bansal. "Heterocyclic Compounds Bearing Triazine Scaffold and Their Biological Significance: A Review." Anti-Cancer Agents in Medicinal Chemistry 20, no. 1 (April 10, 2020): 4–28. http://dx.doi.org/10.2174/1871520619666191028111351.
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Benzene is a six-membered hydrocarbon ring system and if three carbon-hydrogen units of benzene ring are replaced by nitrogen atoms then triazine is formed. Triazines are present in three isomeric forms 1,2,3- triazine, 1,2,4-triazine, and 1,3,5-triazine according to the position of the nitrogen atom. These are weak bases having weaker resonance energy than benzene, so nucleophilic substitution is preferred than electrophilic substitution. Triazine is an interesting class of heterocyclic compounds in medicinal chemistry. Numerous synthetic derivatives of triazine have been prepared and evaluated for a wide spectrum of biological activities in different models with desired findings such as antibacterial, antifungal, anti-cancer, antiviral, antimalarial, antiinflammatory, antiulcer, anticonvulsant, antimicrobial, insecticidal and herbicidal agents. Triazine analogs have exposed potent pharmacological activity. So, triazine nucleus may be considered as an interesting core moiety for researchers for the development of future drugs.
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Birt, J., M. Hadi, N. Sargalo, E. Brookes, P. Swinburn, L. Hanrahan, K. Tse, et al. "THU0253 FATIGUE AND PAIN REMAIN PROMINENT AND IMPACTFUL IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS (SLE): A CROSS-SECTIONAL SURVEY OF SLE PATIENTS IN THE UNITED STATES." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 353.2–354. http://dx.doi.org/10.1136/annrheumdis-2020-eular.4190.
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Background:Systemic lupus erythematosus (SLE) is a chronic autoimmune inflammatory condition impacting multiple organ systems.1,2SLE affects approximately 1.5 million Americans, disproportionately females of reproductive age, and is more prevalent in non-Caucasian populations.3Fatigue and pain are some of the most prominent symptoms of SLE, contributing to the heavy disease burden and disruption to daily life.4This study aimed to further understand the burden of SLE. Lilly worked with the Lupus Foundation of America (LFA) and Evidera to develop the SLE-UPDATE (Understanding Preferences, Disease Activity and Treatment Expectations) survey.Objectives:To understand the patient-perceived symptom burden of SLE, in particular pain and fatigue, within the current landscape of therapeutic options. This study also focused on current treatment patterns in SLE patients.Methods:This was a cross-sectional, non-interventional, online survey study conducted in partnership with the LFA. English-speaking United States patients aged ≥18 years with a self-reported diagnosis of SLE completed the survey following online screening and informed consent. Descriptive data are presented by means (standard deviation [SD]) for continuous measures, and frequency (n, %) for dichotomous measures. Demographic, clinical, and patient-reported outcomes were collected including the FACIT-Fatigue (range 0-52, higher scores indicate less fatigue), Pain Numerical Rating Scale (NRS) (0 [none] to 10 [worst imaginable]), Worst Joint Pain NRS (0 [none] to 10 [worst imaginable]), and the LupusPRO, a validated, lupus-specific quality of life (QoL) instrument (range 0-100, higher scores indicate better QoL).Results:A total of 500 patients with SLE completed the survey. Patients were predominantly female (75%), white/Caucasian (76%), with a mean age of 42.6 years and mean disease duration of 11.1 years.Most patients with SLE rated their overall condition as either good (38%) or fair (31%), with 8% rating poor and 7% excellent. Current non-biologic prescription medication use included: antimalarials 42%, corticosteroids 33%, immunosuppressants 33%, nonsteroidal anti-inflammatory drugs (NSAID) 32%, other analgesics 15% and 10% were using tofacitinib. Biologic therapies were being used by only 19%, including intravenous (IV) Benlysta (37%),subcutaneous(SC) Benlysta (25%), rituximab (17%), and 22% were using other biologics. Fatigue was the most commonly reported symptom (69%), with 40% of patients ranking fatigue as their most bothersome SLE symptom. Forty eight percent of patients with current fatigue rated the severity as moderate and 33% as severe. The mean (SD) FACIT-Fatigue score was 22.9 (12.0). The next most commonly reported symptoms were joint stiffness (57%), sleep problems (55%), joint pain/swelling (53%), and muscle pain (52%). Sixty percent of patients reported experiencing pain all or most of the time over the past seven days. A total of 30% of patients with current joint pain/swelling rated it as severe, and 24% of patients with current joint stiffness rated it as severe. The mean scores for Worst pain NRS and Worst Joint Pain NRS were both 5.8 out of 10.The LupusPRO domains indicated by respondents as the most impacted by SLE were Emotional Health, Pain/Vitality, and Lupus Medications.Conclusion:Fatigue, followed by pain and joint stiffness, were the most common patient-reported symptoms contributing to the overall SLE disease burden. Further research could highlight the efforts required to address the inadequacies in treatment and management of pain and fatigue in this patient population.Disclosure of Interests:Julie Birt Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Monica Hadi: None declared, Nashmel Sargalo: None declared, Ella Brookes: None declared, Paul Swinburn: None declared, Leslie Hanrahan: None declared, Karin Tse: None declared, Natalia Bello Vega Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Kirstin Griffing Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Maria Silk Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Laure Delbecque Shareholder of: Eli Lilly and Company, Employee of: Eli Lilly and Company, Diane L Kamen Consultant of: Consulted on SLE survey development for Lilly and consulted on SLE trial protocol development for EMD Serono in 2019
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Dahalan, Farah Aida, Hasidah Mohd Sidek, Mogana Das Murtey, Mohammed Noor Embi, Jamaiah Ibrahim, Lim Fei Tieng, Nurul Aiezzah Zakaria, and Noraishah Mydin Abdul-Aziz. "Phosphorylated and Nonphosphorylated PfMAP2 Are Localized in the Nucleus, Dependent on the Stage ofPlasmodium falciparumAsexual Maturation." BioMed Research International 2016 (2016): 1–9. http://dx.doi.org/10.1155/2016/1645097.
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Plasmodium falciparummitogen-activated protein (MAP) kinases, a family of enzymes central to signal transduction processes including inflammatory responses, are a promising target for antimalarial drug development. Our study shows for the first time that theP. falciparumspecific MAP kinase 2 (PfMAP2) is colocalized in the nucleus of all of the asexual erythrocytic stages ofP. falciparumand is particularly elevated in its phosphorylated form. It was also discovered that PfMAP2 is expressed in its highest quantity during the early trophozoite (ring form) stage and significantly reduced in the mature trophozoite and schizont stages. Although the phosphorylated form of the kinase is always more prevalent, its ratio relative to the nonphosphorylated form remained constant irrespective of the parasites’ developmental stage. We have also shown that the TSH motif specifically renders PfMAP2 genetically divergent from the other plasmodial MAP kinase activation sites using Neighbour Joining analysis. Furthermore, TSH motif-specific designed antibody is crucial in determining the location of the expression of the PfMAP2 protein. However, by using immunoelectron microscopy, PPfMAP2 were detected ubiquitously in the parasitized erythrocytes. In summary, PfMAP2 may play a far more important role than previously thought and is a worthy candidate for research as an antimalarial.
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Parrulli, S., M. Cozzi, M. Airaldi, F. Romano, F. Viola, P. Sarzi-Puttini, G. Staurenghi, and A. Invernizzi. "POS1393 QUANTITATIVE AUTOFLUORESCENCE FINDINGS IN PATIENTS UNDERGOING HYDROXYCHLOROQUINE TREATMENT." Annals of the Rheumatic Diseases 80, Suppl 1 (May 19, 2021): 979.1–979. http://dx.doi.org/10.1136/annrheumdis-2021-eular.2022.
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Background:Hydroxychloroquine (HCQ) is a relatively safe and effective drug widely used as primary or adjunctive treatment for several rheumatological and dermatological disorders1. HCQ modulates immune response through several mechanisms and has a tropism for pigmented ocular tissues, particularly retinal pigment epithelium (RPE)2. Its accumulation within RPE cells can lead to sight threatening retinal toxicity, with bull’s eye maculopathy (BEM) representing its advanced phenotype. 3 Quantitative Auto-Fluorescence (qAF) is an imaging modality that allows the measurement of retinal auto-fluorescence following short-wavelength light (488nm) excitation of retinal fluorophores (lipofuscin). 4 Two recent studies have focused on qAF values in patients treated with HCQ 5,6. In both cases qAF was increased in eyes with BEM. Furthermore, Reichel et al.6 were able to detect increased values of qAF in patients without BEM as early as 6 months after the start of HCQ treatment using an experimental imaging analysis procedure.Objectives:To measure quantitative autofluorescence (qAF) in patients under treatment with hydroxychloroquine (HCQ) with no apparent signs of retinal toxicity and to compare it with that of untreated subjects.Methods:Consecutive patients at risk for the development of HCQ retinal toxicity (duration of treatment >5 years or daily HCQ dose >5 mg/kg of actual body weight (ABW) and/or renal insufficiency)7 but no alterations on Spectral Domain - Optical Coherence Tomography, Short-Wavelength Autofluorescence and 10-2 Visual Field examination were recruited. Healthy subject matched by age and sex were also enrolled in the study. All subjects underwent qAF measurements in one eye. Images were analyzed using the conventional qAF grid by Delori calculating the qAF of 8 sectors of the intermediate ring and the mean of those values (qAF8).Results:Thirty-nine patients treated with HCQ (38 females, mean age 52,1 ± 8,6 years) and 39 untreated subjects (38 females, mean age 51,2 ± 8,6 years). In both HCQ patients and untreated subjects, qAF8 was positively correlated with age (p=0.004) (Figure 1). Although HCQ patients showed a higher mean qAF8 compared to untreated subjects (294,7 ±65,3 vs 268,9 ± 57,5), the difference was not significant (p=0.068). HCQ patients showed significantly higher mean qAF values in the inferior-temporal, inferior and inferior-nasal sectors of the intermediate ring of qAF grid compared to untreated subjects (all p<0.05).Figure 1.Visual representation of a model predicting the standardized qAF values as influenced by age and HCQ daily dose/ABW, calculated for a treatment duration of 15 years.Conclusion:These results suggest a possible preclinical increase of qAF values in inferior parafoveal sectors probably induced by HCQ exposure. Further studies are required to improve our understanding of preclinical stages of HCQ retinopathy and the possible role of qAF in the HCQ toxicity screening.References:[1]Haładyj, E., Sikora, M., Felis-Giemza, A. & Olesińska, M. Antimalarials - are they effective and safe in rheumatic diseases? Reumatologia56, 164–173 (2018).[2]Rosenthal, A. R., Kolb, H., Bergsma, D., Huxsoll, D. & Hopkins, J. L. Chloroquine retinopathy in the rhesus monkey. Invest. Ophthalmol. Vis. Sci.17, 1158–1175 (1978).[3]Modi, Y. S. & Singh, R. P. Bull’s-Eye Maculopathy Associated with Hydroxychloroquine. N. Engl. J. Med.380, 1656 (2019).[4]Sparrow, J. R., Duncker, T., Schuerch, K., Paavo, M. & de Carvalho, J. R. L. J. Lessons learned from quantitative fundus autofluorescence. Prog. Retin. Eye Res.74, 100774 (2020).[5]Greenstein, V. C. et al. Quantitative Fundus Autofluorescence in HCQ Retinopathy. Invest. Ophthalmol. Vis. Sci.61, 41 (2020).[6]Reichel, C. et al. Quantitative Fundus Autofluorescence in Systemic Chloroquine/Hydroxychloroquine Therapy. Transl. Vis. Sci. Technol.9, 42 (2020).[7]Yusuf, I. H., Sharma, S., Luqmani, R. & Downes, S. M. Hydroxychloroquine retinopathy. Eye (Lond).31, 828–845 (2017).Disclosure of Interests:Salvatore Parrulli: None declared, Mariano Cozzi Grant/research support from: Bayer, Nidek, Zeiss, Matteo Airaldi: None declared, Francesco Romano: None declared, Francesco Viola: None declared, Piercarlo Sarzi-Puttini: None declared, Giovanni Staurenghi Grant/research support from: Heidelberg Engineering (C), QuantelMedical (C), Centervue (C), Carl Zeiss Meditec (C), Alcon (C), Allergan (C), Bayer (C), Boheringer (C), Genentech (C), GSK (C),Novartis (C), and Roche (C), Optos (F), Optovue (F) and Centervue (F), Alessandro Invernizzi Grant/research support from: Novartis (C), Bayer (C)
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Guo, Jin, Armand W. Guiguemde, Annael Bentura-Marciano, Julie Clark, Richard K. Haynes, Wing-Chi Chan, Ho-Ning Wong, Nicholas H. Hunt, R. Kiplin Guy, and Jacob Golenser. "Synthesis of Artemiside and Its Effects in Combination with Conventional Drugs against Severe Murine Malaria." Antimicrobial Agents and Chemotherapy 56, no. 1 (October 17, 2011): 163–73. http://dx.doi.org/10.1128/aac.05006-11.
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ABSTRACTThis research describes the use of novel antimalarial combinations of the new artemisinin derivative artemiside, a 10-alkylamino artemisinin. It is a stable, highly crystalline compound that is economically prepared from dihydroartemisinin in a one-step process. Artemiside activity was more pronounced than that of any antimalarial drug in use, both inPlasmodium falciparumculture andin vivoin a murine malaria model depicting cerebral malaria (CM).In vitrohigh-throughput testing of artemiside combinations revealed a large number of conventional antimalarial drugs with which it was additive. Following monotherapy in mice, individual drugs reduced parasitemias to nondetectable levels. However, after a period of latency, parasites again were seen and eventually all mice became terminally ill. Treatment with individual drugs did not prevent CM in mice with recrudescent malaria, except for piperaquine at high concentrations. Even when CM was prevented, the mice developed later of severe anemia. In contrast, most of the mice treated with drug combinations survived. A combination of artemiside and mefloquine or piperaquine may confer an optimal result because of the longer half life of both conventional drugs. The use of artemiside combinations revealed a significant safety margin of the effective artemiside doses. Likewise, a combination of 1.3 mg/kg of body weight artemiside and 10 mg/kg piperaquine administered for 3 days from the seventh day postinfection was completely curative. It appears possible to increase drug concentrations in the combination therapy without reaching toxic levels. Using the drug combinations as little as 1 day before the expected death of control animals, we could prevent further parasite development and death due to CM or anemic malaria. Earlier treatment may prevent cognitive dysfunctions which might occur after recovery from CM.
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Szumilak, Marta, and Andrzej Stanczak. "Cinnoline Scaffold—A Molecular Heart of Medicinal Chemistry?" Molecules 24, no. 12 (June 18, 2019): 2271. http://dx.doi.org/10.3390/molecules24122271.
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The cinnoline nucleus is a very important bicyclic heterocycle that is used as the structural subunit of many compounds with interesting pharmaceutical properties. Cinnoline derivatives exhibit broad spectrum of pharmacological activities such as antibacterial, antifungal, antimalarial, anti-inflammatory, analgesic, anxiolytic and antitumor activities. Some of them are under evaluation in clinical trials. In the present review, we have compiled studies focused on the biological properties of cinnoline derivatives conducted by many research groups worldwide between 2005 and 2019. Comprehensive and target oriented information clearly indicate that the development of cinnoline based molecules constitute a significant contribution to the identification of lead compounds with optimized pharmacodynamic and pharmacokinetic properties.
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Desai, Sanjay A. "Insights Gained fromP. falciparumCultivation in Modified Media." Scientific World Journal 2013 (2013): 1–6. http://dx.doi.org/10.1155/2013/363505.
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In vitrocultivation ofPlasmodium falciparum, the agent of severe human malaria, has enabled advances in basic research and accelerated the development of new therapies. Since the introduction ofin vitroparasite culture nearly 40 years ago, most workers have used a medium consisting of RPMI 1640 medium supplemented with lipids and hypoxanthine. While these standardized conditions yield robust parasite growth and facilitate comparison of results from different studies, they may also lead to implicit assumptions that limit future advances. Here, I review recent studies that used modified culture conditions to challenge these assumptions and explore parasite physiology. The findings are relevant to understandingin vivoparasite phenotypes and the prioritization of antimalarial targets.
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Ahmad, Siti Junaidah, Mohd Badrin Hanizam Abdul Rahim, Syarul Nataqain Baharum, Mohd Shukri Baba, and Noraziah Mohamad Zin. "Discovery of Antimalarial Drugs from Streptomycetes Metabolites Using a Metabolomic Approach." Journal of Tropical Medicine 2017 (2017): 1–7. http://dx.doi.org/10.1155/2017/2189814.
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Natural products continue to play an important role as a source of biologically active substances for the development of new drug.Streptomyces, Gram-positive bacteria which are widely distributed in nature, are one of the most popular sources of natural antibiotics. Recently, by using a bioassay-guided fractionation, an antimalarial compound, Gancidin-W, has been discovered from these bacteria. However, this classical method in identifying potentially novel bioactive compounds from the natural products requires considerable effort and is a time-consuming process. Metabolomics is an emerging “omics” technology in systems biology study which integrated in process of discovering drug from natural products. Metabolomics approach in finding novel therapeutics agent for malaria offers dereplication step in screening phase to shorten the process. The highly sensitive instruments, such as Liquid Chromatography-Mass Spectrophotometry (LC-MS), Gas Chromatography-Mass Spectrophotometry (GC-MS), and Nuclear Magnetic Resonance (1H-NMR) spectroscopy, provide a wide range of information in the identification of potentially bioactive compounds. The current paper reviews concepts of metabolomics and its application in drug discovery of malaria treatment as well as assessing the antimalarial activity from natural products. Metabolomics approach in malaria drug discovery is still new and needs to be initiated, especially for drug research in Malaysia.
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Munedzimwe, Tatenda C., Robyn L. van Zyl, Donovan C. Heslop, Adrienne L. Edkins, and Denzil R. Beukes. "Semi-Synthesis and Evaluation of Sargahydroquinoic Acid Derivatives as Potential Antimalarial Agents." Medicines 6, no. 2 (April 1, 2019): 47. http://dx.doi.org/10.3390/medicines6020047.
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Background: Malaria continues to present a major health problem, especially in developing countries. The development of new antimalarial drugs to counter drug resistance and ensure a steady supply of new treatment options is therefore an important area of research. Meroditerpenes have previously been shown to exhibit antiplasmodial activity against a chloroquinone sensitive strain of Plasmodium falciparum (D10). In this study we explored the antiplasmodial activity of several semi-synthetic analogs of sargahydroquinoic acid. Methods: Sargahydroquinoic acid was isolated from the marine brown alga, Sargassum incisifolium and converted, semi-synthetically, to several analogs. The natural products, together with their synthetic derivatives were evaluated for their activity against the FCR-3 strain of Plasmodium falciparum as well as MDA-MB-231 breast cancer cells. Results: Sarganaphthoquinoic acid and sargaquinoic acid showed the most promising antiplasmodial activity and low cytotoxicity. Conclusions: Synthetic modification of the natural product, sargahydroquinoic acid, resulted in the discovery of a highly selective antiplasmodial compound, sarganaphthoquinoic acid.
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Kitchen, Lynn W., David W. Vaughn, and Donald R. Skillman. "Reviews Of Anti‐infective Agents: Role of US Military Research Programs in the Development of US Food and Drug Administration–Approved Antimalarial Drugs." Clinical Infectious Diseases 43, no. 1 (July 2006): 67–71. http://dx.doi.org/10.1086/504873.
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Maestre, Amanda, and Jaime Carmona-Fonseca. "Immune responses during gestational malaria: a review of the current knowledge and future trend of research." Journal of Infection in Developing Countries 8, no. 04 (April 15, 2014): 391–402. http://dx.doi.org/10.3855/jidc.3777.
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Women pregnant with their first child are susceptible to severe P. falciparum disease from placental malaria because they lack immunity to placenta-specific cytoadherence proteins. In subsequent pregnancies, as immunity against placental parasites is acquired, there is a reduced risk of adverse effects of malaria on the mother and fetus and asymptomatic parasitaemia is common. In the case of vivax malaria, with increasing reports of severe cases in Asia and South America, the effects of infection by this species during pregnancy remain to be elucidated. This review summarized the main aspects involved in the acquisition of specific antimalarial immune responses during pregnancy with emphasis in research carried out in America and Asia, in order to offer a framework of interpretation for studies on pregnant women with malaria which are recently being produced in these regions. The authors conclude that (1) Effective humoral responses during gestational malaria are mainly directed against variant surface antigens codified by genes of the var2Csa family of P. falciparum; (2) Acquisition of immunity against these variant antigens depends on the degree and intensity of transmission, and the chance increases with age and successive pregnancies; (3) Antibody development is guided by specific cellular immune responses in cases of placental and maternal infection, and (4) The study of the significance of acquisition of specific immunity against both P. falciparum and P. vivax in America, should be performed.
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Sharma, Anjali, Sharad Wakode, Faizana Fayaz, Shaik Khasimbi, Faheem H. Pottoo, and Avneet Kaur. "An Overview of Piperazine Scaffold as Promising Nucleus for Different Therapeutic Targets." Current Pharmaceutical Design 26, no. 35 (October 16, 2020): 4373–85. http://dx.doi.org/10.2174/1381612826666200417154810.
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Piperazine scaffolds are a group of heterocyclic atoms having pharmacological values and showing significant results in pharmaceutical chemistry. Piperazine has a flexible core structure for the design and synthesis of new bioactive compounds. These flexible heterogenous compounds exhibit various biological roles, primarily anticancer, antioxidant, cognition enhancers, antimicrobial, antibacterial, antiviral, antifungal, antiinflammatory, anti-HIV-1 inhibitors, antidiabetic, antimalarial, antidepressant, antianxiety and anticonvulsant activities, etc. In the past few years, researchers focused on the therapeutic profile of piperazine synthons for different biological targets. The present review highlights the development in designing pharmacological activities of nitrogen-containing piperazine moiety as a therapeutic agent. The extensive popularity of piperazine as a drug of abuse and their vast heterogeneity research efforts over the last years motivated the new investigators to further explore this area.
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Mukhamatkhanova, Rimma Fail'yevna, Khayrulla Mamadievich Bobakulov, Il'dar Dzhamil'yevich Sham’yanov, Rasul Yangiberdievich Оkmanov, Haji Akber Aisa, Shomansur Shahsaidovich Sagdullaev, and Nasrulla Dzhalilovich Аbdullaev. "COMPONENTS OF ARTEMISIA SOGDIANA." chemistry of plant raw material, no. 1 (March 5, 2020): 207–14. http://dx.doi.org/10.14258/jcprm.2020015548.
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Phytochemical research and effective use of medicinal flora in the future create the basis for the development of the domestic pharmaceutical industry and allow not only to fill the deficit of drugs, but also contribute to the development of new, environmentally friendly and a number of qualities of unique, export-oriented preparations.
The plants of the genus Artemisia L. are rich sources of biologically active secondary metabolites. Phytochemical study of secondary metabolites of plants of the genus Artemisia has led to the creation on their basis, in particular, on the sesquiterpene lactones, antitumor (Artemisinin and its derivatives; Arglabin), antiatherosclerotic (Leucomisin (preparation Oligvon)), cardiotonic (Tauremisin), anthelmintic (α-Santonin) and antimalarial (Artemisinin and its derivatives) preparations.
In order to search for natural biologically active compounds, we studied the components of the alcohol extract of the aerial part of Artemisia sogdiana Bunge, collected during budding in the Zaamin district of the Jizzakh region of Uzbekistan. The result of phytochemical research for the first time from this plant is isolated a phenolic compound xanthoxylin, sesquiterpene lactone artesin, flavonoids genkwanin and eupatilin, the structure of which is established on the basis of spectral data.
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Gurjar, Vinod Kumar, and Dilipkumar Pal. "RECENT DEVELOPMENTS AND MULTIPLE BIOLOGICAL ACTIVITIES AVAILABLE WITH 1, 8-NAPHTHYRIDINE DERIVATIVES: A REVIEW." International Journal of Pharmacy and Pharmaceutical Sciences 10, no. 8 (August 1, 2018): 1. http://dx.doi.org/10.22159/ijpps.2018v10i8.27006.
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The 1,8-naphthyridine derivatives have gained special attention from researchers nowadays on account of their demonstrating a variety of interesting biological activities. A wide range of biological activities establishes them as potent scaffolds in therapeutic and medicinal research. The broad spectrum of activities primarily includes antimicrobial, antiviral, anti-inflammatory, anticancer, antihypertensive and analgesic activities. 1,8-Naphthyridine derivatives have also exhibited potential applications in neurological disorders such as Alzheimer’s disease and depression. In addition, these synthetic derivatives have been found to possess activities such as anti-HIV, anti-osteoporotic, αvβ3 antagonism, anti-allergic, antimalarial, gastric antisecretory, anticonvulsant, platelet aggregation inhibition, anti-oxidant, Epidermal Growth Factor Receptor (EGFR) inhibition, protein kinase inhibition, ionotropic properties, β3 antagonism, phosphodiesterase 4 (PDE 4) inhibition, adenosine receptor agonist, adrenoceptors antagonism and DNA stabilizing properties. In this review, we present an update of different 1,8-naphthyridine derivatives and discuss the key data available in the context of various biological activities of 1,8-naphthyridine derivatives available from the literature. This may direct future researches in the synthesis of new derivatives of it and exploring this scaffold for modification of existing biological actions as well as evaluation of other possible pharmacological activities.
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Rokiban, Akhmad, Ramadhan Triyandi, and Karnila Sari. "EVALUATION OF THE USE OF ANTIMALARIA MEDICINES IN HANURA HEALTH CENTRE PESAWARAN DISTRICT PERIOD JANUARY-DECEMBER IN 2018." JFL: Jurnal Farmasi Lampung 9, no. 1 (March 13, 2021): 36–43. http://dx.doi.org/10.37090/jfl.v9i1.330.
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Abstract Malaria is a public health problem in Indonesia, especially those living in isolated areas. This is published in Presidential Regulation No. 5/2010 concerning the National Medium Term Development Plan for malaria endemic areas, which are divided into high, medium and low endemic areas. High endemic if the API is greater than 50 out of 1,000 population in the provinces of Maluku, Papua, North Sumatra and East Nusa Tenggara. Moderate endemic if the API is 1 to less than 50 dari 1,000 population in the provinces of Aceh, Bangka Belitung, Jambi and West Nusa Tenggara. Low endemic if the API is 0-1 per 1,000 population in Kalimantan, Sulawesi, and parts of Java. This study aims to determine the evaluation of the use of antimalarial drugs with the characteristics of age, sex, and type of malaria plasmodium at the Hanura Public Health Centre based on the criteria of the right indication, the right drug, the right dose, the right interval of drug administration (4T). This research is a descriptive research with purposive sampling method. Collection of prescription data and medical records in January-December 2018. The results showed that in cases of Malaria based on age, the most common cases occurred in the age range of 56-65 years, amounting to 99.6%, based on sex experienced in men by 77.41%, based on body weight the most occurred at 41-59 kg at 45.16%, based on the type of plasmodium experienced plasmodium vivax mostly at 84.95%. Based on these data, it was concluded that the evaluation of the use of antimalarial drugs based on 4T criteria was 100% accurate indication, 100% correct drug, 72.04% correct dose, 98.92% correct interval of drug administration. Keywords: Malaria vivax, treatment, Puskesmas, 4T
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Figueroa-Parra, G., A. Moreno-Salinas, C. M. Gamboa-Alonso, A. L. De-Leon-Ibarra, D. Á. Galarza-Delgado, and J. A. Esquivel Valerio. "AB0432 CLINICAL AND SEROLOGICAL CHARACTERISTICS OF “RHUPUS SYNDROME”." Annals of the Rheumatic Diseases 79, Suppl 1 (June 2020): 1515.2–1515. http://dx.doi.org/10.1136/annrheumdis-2020-eular.6440.
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Background:Systemic lupus erythematosus (SLE) is a multisystemic and chronic autoimmune disorder that typically affects (1). Arthritis is one of the most frequent manifestations in SLE with an incidence reported from 69% to 95% (2). Rheumatoid arthritis (RA) is an articular, inflammatory, chronic disease of autoimmune nature (3). Rhupus syndrome is defined as a patient that meets the classification criteria for RA of the American College of Rheumatology (ACR) of 1987 and for SLE of the ACR of 1982, in addition, necessarily erosive arthropathy with antibodies specific for positive SLE (anti-Sm or anti-DNAdc) (4). With the development of more recent classification criteria for both RA and SLE, which allow us to detect both diseases earlier, they create even more heterogeneity in the definition of rhupus, being a rare entity, the analysis of the clinical and serological characteristics of this population in our clinic would provide data to the few existing.Objectives:To describe the clinical and serological characteristics of patients with Rhupus.Methods:An observational, retrospective study was done in the rheumatology clinic of the university hospital “Dr. Jose Eleuterio Gonzalez” in Monterrey, Mexico. The electronic medical record (EMR) was reviewed. In search of the term “rhupus”. All the patients were analyzed individually to verify the rhupus diagnosis. The main clinical and serological characteristics were evaluated. The results are shown in descriptive statistics.Results:30 patients were obtained from the search in the EMR, 22 patients were included, 8 patients were excluded (5 non-SLE, 3 non-RA) (Figure 1). The mean age was 40.14 (SD 10.86); 20 (90.9%) were females; the onset diagnosis was SLE in 5 (22.7%), RA in 14 (63.6%) and both 3 (13.6%). 17 (77.3%) had general symptoms, 12 (54.5%) had cutaneous manifestations, 14 (66.6%) had renal manifestations, 6 (27.3%) had serositis, 19 (86.3%) had hematologic manifestations, 3 (13.6%) had neuropsychiatric manifestations, 1 (4.5%) had diffuse alveolar hemorrhage. 12 (60%) had anti-dsDNA positive, 4 (23.5%) had anti-Sm positive, 16 (84.2%) had anti-CCP positive (Table 1). The articular manifestations (swollen and tender joints at onset and at last visit) are detailed in Table 2. The treatments were different at the onset of the disease compared with the last visit, except for methotrexate (Table 2).Table 1.Clinical and serological characteristics.N=22Female, n (%)20 (90.9)Age, mean (SD)40.14 (10.86)Onset diagnosisSLE, n (%)5 (22.7)RA, n (%)14 (63.6)Both, n (%)3 (13.6)ManifestationsGeneral, n (%)17 (77.3)Cutaneous, n (%)12 (54.5)Renal, n (%)14 (66.6)Serositis, n (%)6 (27.3)Hematological, n (%)19 (86.3)Neuropsychiatric, n (%)3 (13.6)Diffuse alveolar hemorrhage, n (%)1 (4.5)SerologyAnti-dsDNA (N=20), n (%)12 (60)Anti-Sm (N=17), n (%)4 (23.5)Anti-CCP (N=19), n (%)16 (84.2)Table 2.Disease activity and treatment.At onset N=22Last visit N=22Swollen joints, mean (SD)9.3 (6.6)3.0 (4.8)Tender joints, mean (SD)8.5 (7.1)1.59 (3.8)VAS, mean (SD)42 (33.6)17.2 (21.1)PGA, mean (SD)38 (32.3)16.6 (20.3)Activity scalesSLEDAI-2k, mean (SD)8.38 (4.5)2.9 (3.2)DAS28-VSG, mean (SD)5.26 (1.51)2.89 (0.83)TreatmentGlucocorticoid, n (%)21 (95.4)15 (68.2)Antimalarials, n (%)17 (77.2)11 (50)Immunosuppressants, n (%)8 (36.3)2 (9.1)Methotrexate, n (%)16 (72.7)16 (72.7)Leflunomide, n (%)4 (18.2)5 (22.7)Sulfasalazine, n (%)5 (22.7)0 (0)Figure 1.Conclusion:In our cohort, rhupus affects more frequently females, the hematologic manifestations are very frequent and the neuropsychiatric and diffuse alveolar hemorrhage was rare.References:[1]Nat Rev Dis Primers. 2016;2(1):1-21.[2]Best Practice & Research Clinical Rheumatology. 2009;23(4):495-506.[3]Nat Rev Dis Primers. 2018;4(1):1-23.[4]Lupus. 2002;11(5):287-292.Disclosure of Interests:None declared