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• W97051736 startingPage "937" @default.
• W97051736 abstract "African trypanosomes (Trypanosoma brucei species) are parasitic protozoa that cause lethal diseases in humans and cattle. Previous studies showed that camptothecin, a potent and specific inhibitor of DNA topoisomerase I, is cytotoxic to African trypanosomes and related pathogenic hemoflagellates (Bodley AL and Shapiro TA, Proc Natl Acad Sci USA92: 3726–3730, 1995). In this study, a series of camptothecin analogs was tested against axenically cultured, bloodstream form, T. brucei. Modifications to the pentacyclic nucleus of camptothecin ablated antiparasitic activity. In contrast, activity could be increased by substituents added to the parent ring system (e.g. 10,11-methylenedioxy or ethylenedioxy groups; alkyl additions to carbon 7; or 9-amino or 9-chloro substituents). Cytotoxicity was correlated with the level of cleavable complexes in trypanosomes, implicating topoisomerase I as the intracellular target for these compounds. To obtain some indication of selective toxicity, ten compounds were also tested against L1210 mouse leukemia cells. The 9-substituted-10, 11-methylenedioxy analogs caused a disproportionate increase in antiparasitic activity, compared with mammalian cell toxicity. These findings provide a basis for designing further structural modifications and for selecting camptothecin analogs to test in animal models of trypanosomiasis." @default.
• W97051736 created "2016-06-24" @default.
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• W97051736 date "1995-09-01" @default.
• W97051736 modified "2023-09-27" @default.
• W97051736 title "Antitrypanosomal activity of camptothecin analogs" @default.
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• W97051736 doi "https://doi.org/10.1016/0006-2952(95)00215-l" @default.
• W97051736 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/7575676" @default.
• W97051736 hasPublicationYear "1995" @default.
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