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.
| Original language | English |
|---|---|
| Pages (from-to) | 1485-1497 |
| Number of pages | 13 |
| Journal | Future Medicinal Chemistry |
| Volume | 16 |
| Issue number | 15 |
| Early online date | 2 Jul 2024 |
| DOIs | |
| Publication status | E-pub ahead of print - 2 Jul 2024 |
Funding
We acknowledge the UK Research and Innovation\u2019s Global Challenges Research Fund, under the project agreement \u2018A Global Network for Neglected Tropical Diseases\u2019 (grant MR/P027989/1), for part funding of the project. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.
| Funders | Funder number |
|---|---|
| UK Research and Innovation | MR/P027989/1 |
Keywords
- (±)-Aminoglutethimide
- cutaneous leishmaniasis
- cytotoxicity
- thiourea
ASJC Scopus subject areas
- Drug Discovery
- Molecular Medicine
- Pharmacology