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 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.