Synthesis of quinoline derivatives as potential cysteine protease inhibitors

Abstract

Aim: Cysteine proteases are important molecular targets involved in the replication, virulence and survival of parasitic organisms, including Trypanosoma and Leishmania species. Methodology & results: Analogs of the 7-chloro-N-[3-(morpholin-4-yl)propyl]quinolin-4-amine were synthesized and their inhibitory activity against the enzymes cruzain and rhodesain as well as against promastigotes forms of Leishmania species and epimastigotes forms of Trypanosoma cruzi were evaluated. Five compounds showed activity against both enzymes with half maximal inhibitory concentration (IC₅₀) values ranging from 23 to 123 μM. Among these, compounds 3 and 4 displayed leishmanicidal activity; compound 4 was the most promising with IC₅₀ values <10 μM and no cytotoxicity for uninfected cells. Conclusion: The results obtained indicate that cysteine proteases are likely to be the molecular target of compounds 3 and 4.

Keywords: 4-aminoquinolines; antiparasitic activity; cysteine protease.