Antileishmanial ferrocenylquinoline derivatives: Synthesis and biological evaluation against Leishmania donovani

The emergence of resistance against existing antileishmanial drugs necessitates the search for new classes of antileishmanial compounds. Herein a series of structurally diverse ferrocenylquinolines have been synthesized and evaluated for in vitro antileishmanial activity against Leishmania donovani using the MTT assay. Thirteen (M2-M14) substituted ferrocenylquinoline congeners possessing triazole rings were generated by palladium mediated Suzuki-Miyaura coupling reaction of 5-iodoferrocenylquinolinetriazole and substituted arylboronic acids. All the synthesized compounds were tested for its antileishmanial activity using both promastigote and amastigote stages of L donovani. Among them, three compounds (M4, M7 and M9) exhibited promising anti-promastigote activity, with an IC50 value of 28.7 mu M, 22.1 mu M and 28 mu M, respectively, and no cytotoxicity toward host splenocytes. These three compounds are equally effective against the intracellular amastigote stage of L. donovani showing the IC50 values of 16 mu M (M4), 8 mu M (M7) and 16 mu M (M9), respectively, with consistent nitric oxide generation as required for parasite clearance. From the battery of tests conducted in this study, it appears that these compounds induce parasite death by promoting cell cycle arrest and triggering apoptosis. (C) 2016 Elsevier Masson SAS. All rights reserved.