1. Thiourea-functionalized aminoglutethimide derivatives as anti-leishmanial agents.
- Author
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Sajid M, Siddiqui H, Zafar H, Yousuf S, Threadgill MD, and Choudhary MI
- Subjects
- Structure-Activity Relationship, Molecular Docking Simulation, Humans, Parasitic Sensitivity Tests, Molecular Structure, Animals, Thiourea pharmacology, Thiourea chemistry, Thiourea analogs & derivatives, Thiourea chemical synthesis, Antiprotozoal Agents pharmacology, Antiprotozoal Agents chemistry, Antiprotozoal Agents chemical synthesis, Leishmania major drug effects, Leishmania tropica drug effects
- 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 (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.- Published
- 2024
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