Clotrimazole causes membrane depolarization and induces sub G < sub > 0 < /sub > cell cycle arrest in Leishmania donovani

In this study we have explored the possibility of repurposing clotrimazole as an antileishmanial drug. We have assessed its efficacy on the parasites and attempted to understand its mode of action. We found that it has a half-maximal inhibitory concentration (IC50) of 35.75 ± 1.06 μM, 12.75 ± 0.35 μM and 73 ± 1.41 μM in promastigotes, intracellular amastigotes and macrophages, respectively. Clotrimazole is 5.73 times more selective for the intracellular amastigotes as compared to the mammalian cell. Effect of clotrimazole was reduced by ergosterol supplementation. It leads to impaired parasite morphology. It alters plasma membrane permeability and disrupts plasma membrane potential. Mitochondrial function is compromised as is evident from increased ROS generation, depolarized mitochondrial membrane and decreased ATP levels. Cell cycle analysis of clotrimazole treated parasites shows arrest at sub-G0 phase suggesting apoptotic mode of cell death.PMID:38307362 | DOI:10.1016/j.actatropica.2024.107139
Source: Acta Tropica - Category: Infectious Diseases Authors: Source Type: research