Article

Projet
Conception, synthèse et étude de nouveaux hétérocycles azotés d'intérêts biologiques  
Ahcène BOUMENDJELMarine PEUCHMAURBenjamin BOUCHERLE,   
Titre
Arylthiosemicarbazones as antileishmanial agents  
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Auteurs
J. I. Manzano, F. Cochet, B. Boucherle, V. Gómez-Pérez, A. Boumendjel, F. Gamarro, M. Peuchmaur
Edition
Eur. J. Med. Chem. 2016, 123, 161-170.
Année
2016
Résumé
Based on a screening process, we targeted substituted thiosemicarbazone as potential antileishmanial agents. Our objective was to identify the key structural elements contributing to the anti-parasite activity that might be used for development of effective drugs. A series of 32 compounds was synthesized and their efficacy was evaluated against the clinically relevant intracellular amastigotes of Leishmania donovani. From these, 22 compounds showed EC50 values below 10 μM with the most active derivative (compound 14) showing an EC50 of 0.8 μM with very low toxicity on two different mammalian cell lines. The most relevant structural elements required for higher activity indicate that the presence of a fused bicyclic aromatic ring such as a naphthalene bearing an alkyl or an alkoxy group substituent are prerequisites. Owing to the easy synthesis, high activity and low toxicity, the most active compounds could be considered as a lead for further development.