Kojic Acid Promotes Apoptosis-like Death and Cell Cycle Arrest in Leishmania (Leishmania) amazonensis Promastigotes

Leishmaniasis is a group of neglected tropical diseases caused by protozoa of the genus Leishmania that are present in about 90 countries. More than 20 species are responsible for the infection, causing varying clinical manifestations. Leishmaniasis treatment includes pentavalent antimonials that have been used for decades as the first-choice drug. However, due to their severe side effects, high cost, and protozoan resistance, finding new, affordable, and safe drug alternatives for leishmaniasis treatment is necessary. Kojic acid (KA) promotes leishmanicidal activity for both promastigotes and amastigotes, in vitro and in vivo. The objective of this study was to evaluate the mechanism of action of KA on promastigotes of Leishmania (Leishmania) amazonensis. Our findings demonstrate that KA induces direct leishmanicidal effects by promoting apoptosis-like cell death, oxidative stress, ultrastructural changes, and cell cycle disruption in Leishmania (L.) amazonensis promastigotes. These results position KA as a promising candidate for future antileishmanial drug development.