Thiourea-functionalized aminoglutethimide derivatives as anti-leishmanial agents.

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 (IC 50  = 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.