The antimalarial efficacy and mechanism of resistance of the novel chemotype DDD01034957
| العنوان: | The antimalarial efficacy and mechanism of resistance of the novel chemotype DDD01034957 |
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| المؤلفون: | Ernest Diez Benavente, Francisco-Javier Gamo, Jake Baum, Esperanza Herreros, James M. Murithi, David A. Fidock, Fiona Angrisano, Frank Schwach, Susana Campino, Oliver Billker, Katarzyna A. Sala, Andrew M. Blagborough, Taane G. Clark, Michael J. Delves, Manu Vanaerschot, Matthew J. Fuchter, Colin J. Sutherland, Celia Miguel-Blanco, Donelly A. van Schalkwyk |
| المساهمون: | Apollo - University of Cambridge Repository, Bill & Melinda Gates Foundation, Wellcome Trust, Medicines for Malaria Venture, van Schalkwyk, Donelly A [0000-0002-7375-3439], Clark, Taane G [0000-0001-8985-9265] |
| المصدر: | Scientific Reports, Vol 11, Iss 1, Pp 1-9 (2021) Scientific Reports |
| بيانات النشر: | Umeå universitet, Molekylär Infektionsmedicin, Sverige (MIMS), 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | 0301 basic medicine, Drug, Plasmodium, Erythrocytes, Plasmodium berghei, Science, media_common.quotation_subject, Cell- och molekylärbiologi, Plasmodium falciparum, 030106 microbiology, Drug Resistance, Drug resistance, Apicomplexan parasite, Pharmacology, Host-Parasite Interactions, Antimalarials, Inhibitory Concentration 50, Mice, 03 medical and health sciences, Species Specificity, In vivo, medicine, Animals, Humans, 692/699/255/1629, Drug discovery and development, 631/154/309/2144, media_common, Multidisciplinary, Molecular Structure, biology, Mechanism (biology), article, Immunology in the medical area, biology.organism_classification, medicine.disease, Malaria, Cell and molecular biology, 030104 developmental biology, Immunologi inom det medicinska området, Medicine, Cell and Molecular Biology |
| الوصف: | Funder: Public Health England; doi: https://doi.org/10.13039/501100002141 Funder: European Developing Countries Trials Platform Funder: Isaac Newton Trust Funder: Alborada Fund Funder: Global Health Innovative Technology Fund; doi: https://doi.org/10.13039/501100013996 Funder: Royal Society New antimalarial therapeutics are needed to ensure that malaria cases continue to be driven down, as both emerging parasite resistance to frontline chemotherapies and mosquito resistance to current insecticides threaten control programmes. Plasmodium, the apicomplexan parasite responsible for malaria, causes disease pathology through repeated cycles of invasion and replication within host erythrocytes (the asexual cycle). Antimalarial drugs primarily target this cycle, seeking to reduce parasite burden within the host as fast as possible and to supress recrudescence for as long as possible. Intense phenotypic drug screening efforts have identified a number of promising new antimalarial molecules. Particularly important is the identification of compounds with new modes of action within the parasite to combat existing drug resistance and suitable for formulation of efficacious combination therapies. Here we detail the antimalarial properties of DDD01034957—a novel antimalarial molecule which is fast-acting and potent against drug resistant strains in vitro, shows activity in vivo, and possesses a resistance mechanism linked to the membrane transporter PfABCI3. These data support further medicinal chemistry lead-optimization of DDD01034957 as a novel antimalarial chemical class and provide new insights to further reduce in vivo metabolic clearance. |
| وصف الملف: | application/pdf; text/xml |
| اللغة: | English |
| تدمد: | 2045-2322 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::df8efc7f4767c5446f0bb7a7941be9a5 http://urn.kb.se/resolve?urn=urn:nbn:se:umu:diva-180515 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....df8efc7f4767c5446f0bb7a7941be9a5 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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