Antileishmanial Activity of Oseltamivir and Acyclovir: Modulation of Macrophage Phagocytosis and Cytotoxicity Assessment

Abstract

Leishmaniasis is a group of diseases caused by protozoa of the genus Leishmania. Current treatments exhibit high toxicity, high costs, and parasite resistance. Consequently, the search for new drugs is of utmost importance, and drug repositioning may offer an alternative for combating the disease. This study aimed to evaluate the antileishmanial and cytotoxic activities, as well as macrophage activation parameters, of oseltamivir (OSV) and acyclovir (ACV). The substances demonstrated antileishmanial activity. The median inhibitory concentration (IC50) values of OSV against different species (L. amazonensis, L. braziliensis, L. infantum, and L. major) were 252.321, 268.161, 29.207, and 143.859 μg/mL, respectively. For ACV, the IC50 values were 25.726, 45.552, 580.741, and 608.981 μg/mL, respectively. The median cytotoxic concentrations (CC50) of OSV and ACV were 512.17 and 2568.75 μg/mL, respectively. Both OSV and ACV significantly reduced the percentage of infected macrophages, with a selectivity index (SI) >20. Additionally, OSV and ACV increased phagocytic capacity but did not enhance lysosomal activity or significantly induce nitric oxide synthesis. Further investigations are necessary to evaluate these substances in experimental in vivo infection models.