Synthesis, electrochemistry, and in vitro antileishmanial efficacy of novel ferrocenylazines

Abstract

Leishmaniasis is a zoonotic disease prevalent in 83–92 countries. This disease's current treatments are unsatisfactory because of a variety of shortcomings, including serious toxicity, variable efficacy, painful administration, and the occurrence of parasite resistance to these antileishmanial agents. The abovementioned limitations have urged the development of novel, reliable, and affordable agents to treat leishmaniasis. Ferrocenylazine derivatives were therefore synthesized for activity screening against Leishmania major and Leishmania donovani cell cultures. This emphasizes the urgent need for new effective antileishmanial agents. In search for such therapeutics, we synthesized and evaluated in vitro the antileishmanial activity of a series of azine derivatives based on the organometallic compound ferrocene. Two ferrocenylaldazines, 2l and 2q, were uncovered as mammalian cell nontoxic antileishmanial early leads, expressing submicromolar activity with IC50 values of 0.78 ± 0.03 and 0.46 ± 0.03 μM, respectively, against amastigote of L. donovani. Ferrocenylazines may therefore act as potential new antileishmanial agents, and the next objective will be the identification of the involved biological targets.