Design, synthesis and evaluation of novel phenanthridine triazole analogs as potential antileishmanial agents

Abstract

Aim: To synthesize and screen phenanthridine and 1,2,3-triazole derivatives for antileishmanial activity. Methodology: Synthesized analogs were tested for antileishmanial activity against transgenic strain of Leishmania infantum promastigotes and ex vivo infections. Results: Compounds T01, T08 and T11 revealed significant activity with EC50 <30 μm and lacked toxicity in mouse spleen and HepG2 cells. T01 with EC50 3.07 μm is fourfold more potent than the drug miltefosine (EC50 12.6 μM) against L. infantum promastigotes. In silico studies indicate that the analogs are nontoxic. A molecular docking analysis was also carried out on the T01 and T08 to investigate the binding pattern at the active site of the chosen target trypanothione reductase. Conclusion: The results of this study reveal that phenanthridine triazoles exhibit antileishmanial activity.