Ex vivo and In vitro antiplasmodial activities of approved drugs predicted to have antimalarial activities using chemogenomics and drug repositioning approach.
| Autor: | Ochora DO; Department of Biological Sciences, School of Pure and Applied Sciences, Kisii University, P.O. Box 408-40200, Kisii, Kenya.; DSI/NWU, Preclinical Drug Development Platform, Faculty of Health Sciences, North-West University, Private Bag X6001, 2520, Potchefstroom, South Africa.; United States Army Medical Research Directorate-Africa (USAMRD-A), Kenya Medical Research Institute (KEMRI)-Walter Reed Project, P.O. Box 54-40100, Kisumu, Kenya., Mogire RM; Kenya Medical Research Institute (KEMRI) - Kemri-Wellcome Trust Research Programme, P.O. Box 230-80108, Kilifi, Kenya., Masai RJ; Department of Biological Sciences, School of Pure and Applied Sciences, Kisii University, P.O. Box 408-40200, Kisii, Kenya., Yeda RA; United States Army Medical Research Directorate-Africa (USAMRD-A), Kenya Medical Research Institute (KEMRI)-Walter Reed Project, P.O. Box 54-40100, Kisumu, Kenya., Mwakio EW; United States Army Medical Research Directorate-Africa (USAMRD-A), Kenya Medical Research Institute (KEMRI)-Walter Reed Project, P.O. Box 54-40100, Kisumu, Kenya., Amwoma JG; Department of Biological Sciences, University of Embu P. O. Box 6-60100, Embu, Kenya., Wakoli DM; Department of Biochemistry and Molecular Biology, Egerton University, P.O. Box 536-20115, Egerton-Njoro, Kenya., Yenesew A; Department of Chemistry, University of Nairobi, P.O. Box 30197-00100, Nairobi, Kenya., Akala HM; United States Army Medical Research Directorate-Africa (USAMRD-A), Kenya Medical Research Institute (KEMRI)-Walter Reed Project, P.O. Box 54-40100, Kisumu, Kenya. |
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| Jazyk: | angličtina |
| Zdroj: | Heliyon [Heliyon] 2023 Aug 01; Vol. 9 (8), pp. e18863. Date of Electronic Publication: 2023 Aug 01 (Print Publication: 2023). |
| DOI: | 10.1016/j.heliyon.2023.e18863 |
| Abstrakt: | High malaria mortality coupled with increased emergence of resistant multi-drug resistant strains of Plasmodium parasite, warrants the development of new and effective antimalarial drugs. However, drug design and discovery are costly and time-consuming with many active antimalarial compounds failing to get approved due to safety reasons. To address these challenges, the current study aimed at testing the antiplasmodial activities of approved drugs that were predicted using a target-similarity approach. This approach is based on the fact that if an approved drug used to treat another disease targets a protein similar to Plasmodium falciparum protein, then the drug will have a comparable effect on P. falciparum . In a previous study, in vitro antiplasmodial activities of 10 approved drugs was reported of the total 28 approved drugs . In this study, six out of 18 drugs that were previously not tested, namely epirubicin, irinotecan, venlafaxine, palbociclib, pelitinib, and PD153035 were tested for antiplasmodial activity. The drug susceptibility in vitro assays against five P. falciparum reference strains (D6, 3D7, W2, DD2, and F32 ART) and ex vivo assays against fresh clinical isolates were done using the malaria SYBR Green I assay. Standard antimalarial drugs were included as controls. Epirubicin and irinotecan showed excellent antiplasmodial ex vivo activity against field isolates with mean IC Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2023 The Authors.) |
| Databáze: | MEDLINE |
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