Thiourea-functionalized aminoglutethimide derivatives as anti-leishmanial agents
Muhammad Sajid1, Hina Siddiqui1,2, Humaira Zafar3
1H.E.J. Research Institute of Chemistry, International Center for Chemical & Biological Sciences, University of Karachi, Karachi, 75270, Pakistan.
Abstract:
Aim: We aim to develop new anti-leishmanial agents against Leishmania major and Leishmania tropica.Materials & methods: A total of 23 thiourea derivatives of (±)-aminoglutethimide were synthesized and evaluated for in vitro activity against promastigotes of L. major and L. tropica.Results & conclusion: The N-benzoyl analogue 7p was found potent (IC50 = 12.7 μM) against L. major and non toxic to normal cells. The docking studies, indicates that these inhibitors may target folate and glycolytic pathways of the parasite. The N-hexyl compound 7v was found strongly active against both species, and lacked cytotoxicity against normal cells, whereas compound 7r, with a 3,5-bis-(tri-fluoro-methyl)phenyl unit, was active against Leishmania, but was cytotoxic in nature. Compound 7v was thus identified as a hit for further studies.
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