Synthesis and in vitro antitrypanosomatid activity of novel 5-nitroindole-rhodanine conjugates.

Abstract

Aim: Trypanosomatid diseases, leishmaniasis and trypanosomiasis are vector-borne parasitic diseases that can cause death and catastrophic economic losses for millions of people. The growing resistance of trypanosomatid parasites to current treatments highlights the urgent need for new therapeutic agents. This study explored 5-nitroindole-rhodanine conjugates to identify promising new compounds with the potential for future development as antitrypanosomatid treatments.

Materials and methods: The conjugates were synthesized in a multi-step process and evaluated in vitro for antileishmanial activity against Leishmania (L.) donovani and L. major strains. Cytotoxicity was assessed on Vero and THP-1 cells. Due to the taxonomic relation to Trypanosoma spp. the compounds were also screened for in vitro activity against species that cause zoonotic trypanosomiasis.

Results and conclusion: Several hits were found with leishmanicidal activity against both L. donovani and L. major strains. Of these, 3d was identified as a potential early lead that exhibited nanomolar cidal activity against L. major, and greater selectivity than the reference drug amphotericin B. However, the compounds did not have similar activity levels against Trypanosoma spp. Hence, these compounds should be further investigated for their mechanism of action and in vivo antileishmanial activity to determine their potential as a leishmaniasis treatment.