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- W4220838143 abstract "Safe and effective treatments for Chagas disease, a potentially fatal parasitic infection associated with cardiac and gastrointestinal pathology and caused by the kinetoplastid parasite Trypanosoma cruzi, have yet to be developed. Benznidazole and nifurtimox, which are currently the only available drugs against T. cruzi, are associated with severe adverse effects and questionable efficacy in the late stage of the disease. Natural products have proven to be a rich source of new chemotypes for other infectious agents. We utilized a microscopy-based high-throughput phenotypic screen to identify inhibitors of T. cruzi from a library of natural product samples obtained from fungi procured through a Citizen Science Soil Collection Program (https://whatsinyourbackyard.org/) and the Great Lakes (USA) benthic environment. We identified five leucinostatins (A, B, F, NPDG C, and NPDG D) as potent inhibitors of the intracellular amastigote form of T. cruzi. Leucinostatin B also showed in vivo suppression of T. cruzi in a mouse model of Chagas disease. Given prior reports that leucinostatins A and B have antiparasitic activity against the related kinetoplastid Trypanosoma brucei, our findings suggest a potential cross-trypanocidal compound class and provide a platform for the further chemical derivatization of a potent chemical scaffold against T. cruzi." @default.
- W4220838143 created "2022-04-03" @default.
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- W4220838143 date "2022-01-28" @default.
- W4220838143 modified "2023-10-16" @default.
- W4220838143 title "Identification of Leucinostatins from <i>Ophiocordyceps</i> sp. as Antiparasitic Agents against <i>Trypanosoma cruzi</i>" @default.
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- W4220838143 doi "https://doi.org/10.1021/acsomega.1c06347" @default.
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