Robust leishmanicidal upshot of some new diphenyl triazine-based molecules

Abstract

Amongst the neglected tropical diseases, leishmaniasis alone causes 30 000 deaths annually due to the protozoan parasite genus Leishmania. Existing therapies have serious drawbacks in safety, drug resistance, field-adapted application and cost. Therefore, new safer and shorter treatments are an urgent need of the time. Herein, we report the synthesis of fifteen novel diphenyl triazine and diphenyl triazine pyrimidine derivatives and their antileishmanial properties against Leishmania donovani, that causes fatal visceral leishmaniasis. Most of the synthesized analogues exhibited more than 90% inhibition against the promastigote stage of the parasite. Moreover, compounds T4 and T7 showed potent activity against extracellular promastigote (IC₅₀ = 1.074 μM and IC₅₀ = 1.158 μM) as compared to miltefosine (IC₅₀ = 1.477 μM) and is nontoxic towards the host THP-1 macrophage cell line. Interestingly, compound T4 exhibited significant activity against amastigotes (7.186 μM) and induced the macrophages to prevent the survival of the parasite. Our results indicate that T4 represents a new structural lead for this serious and neglected disease.