Repurposing of propafenone, an FDA approved anti-arrhythmic drug for antileishmanial therapy

Abstract

Elimination of the Neglected Tropical Disease Visceral Leishmaniasis (VL) is a Sustainable Development Goal. It is caused by Leishmania donovani. The therapeutic options for the treatment of VL are limited due to problems such as drug resistance and toxicities. Drug repurposing can be a promising alternative in this case. In this work, the antileishmanial potential of FDA approved anti-arrhythmic drug propafenone has been evaluated for repurposing. It reduced the viability of L. donovani promastigotes and intracellular amastigotes with an IC₅₀ of 8.25 ± 2.48 μM and 11.19 ± 0.01 μM respectively. In the macrophages, the IC₅₀ was 32 ± 7.07 μM. Propafenone treatment altered morphology of parasites and induced damage to the body and flagellum. The cell membrane became damaged and more permeable when the promastigotes were treated with this drug. However, no change in the cell membrane potential was detected. Treatment with propafenone was detrimental to mitochondrial health of L. donovani. It significantly depolarized the mitochondrial membrane and decreased the ATP levels in the promastigotes. Propafenone also induced oxidative stress in the parasites. Cell cycle arrest was detected at the G₂/M stage. The data suggests that propafenone has antileishmanial potential and can be evaluated further in an experimental VL model.