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

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 EC 50 <30 μm and lacked toxicity in mouse spleen and HepG2 cells. T01 with EC 50 3.07 μm is fourfold more potent than the drug miltefosine (EC 50 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.