Synthesis and biological evaluation of ferrocenylquinoline as a potential antileishmanial agent.

Abstract

The emergence of resistance against antileishmanial drugs in current use necessitates the search for new classes of antileishmanial compounds. Herein we report the design, synthesis, and evaluation of a novel ferrocenylquinoline for activity against Leishmania donovani. 7-Chloro-N-[2-(1H-5-ferrocenyl-1,2,3-triazol-1-yl)ethyl]quinolin-4-amine (1) was generated by coupling an iron(II) ethynylferrocene species with 4-(2-ethylazido)amino-7-chloroquinoline using click chemistry. The synthesized compound 1 was tested for its antileishmanial activity using both promastigote and amastigote stages of L. donovani. Compound 1 showed promising anti-promastigote activity, with an IC50 value of 15.26 μM and no cytotoxicity toward host splenocytes. From the battery of tests conducted in this study, it appears that this compound induces parasite death by promoting oxidative stress and depolarizing the mitochondrial membrane potential, thereby triggering apoptosis. These results suggest that ferrocenylquinoline 1 is a suitable lead for the development of new antileishmanial drugs.