Synthesis, in vitro Antileishmanial Efficacy and Hit/Lead Identification of Nitrofurantoin-Triazole Hybrids.

Abstract

Leishmaniasis is a vector‐borne neglected parasitic infection affecting thousands of individuals, mostly among populations in low‐ to moderate‐income developing countries. In the absence of protective vaccines, the management of the disease banks solely on chemotherapy. However, the clinical usefulness of current antileishmanial drugs is threatened by their toxicity and the emergence of multidrug‐resistant strains of the causative pathogens. This emphasizes the imperative for the development of new and effective antileishmanial agents. In this regard, we synthesized and evaluated in vitro the antileishmanial activity and cytotoxicity profile of a series of nitrofurantoin‐triazole hybrids. The nitrofurantoin derivative 1 featuring propargyl moiety was distinctively the most active of all, was nontoxic to human cells and possessed submicromolar cellular activity selectively directed towards the pathogens of the life threatening visceral leishmaniasis. Hence it was identified as potential antileishmanial lead for further investigation into its prospective to act as alternative to therapies.