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

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.

Automated summary

Leishmaniasis is a common parasitic infection, especially prevalent among populations in low-income developing countries. The lack of effective vaccines means that chemotherapy is the primary treatment method. However, current antileishmanial drugs are limited due to their toxicity and drug-resistant strains. Therefore, there is a need for new and effective antileishmanial agents. In this study, a series of nitrofurantoin-triazole hybrids were synthesized and evaluated for their activity and cytotoxicity. One derivative, featuring a propargyl moiety, showed the highest activity against the causative pathogens of visceral leishmaniasis, with no toxicity to human cells. This compound has potential as an alternative therapy and warrants further investigation.