New Licarin A Derivative is Effective against Leishmania (Leishmania) amazonensis Promastigotes and Intracellular Amastigotes

Abstract

New therapeutic options against leishmaniasis are necessary, especially those of natural origin, like licarin A, a neolignan with activity against Leishmania major. The effect of licarin A (DL01) and its derivatives (DL03, DL10, DL17 and DL21) was evaluated against Leishmania amazonensis promastigotes and intracellular amastigotes. Promastigote forms were assayed in different incubation periods and the 50% effective concentration (EC50) was determined. Cytotoxicity was assessed in murine peritoneal macrophages by 3-(4,5-dimethylthiazol2-yl)-2,5-diphenyltetrazoliumbromide (MTT) assay to determine the 50.0% cytotoxicity concentrations (CC50). Anti-amastigote activity was evaluated through the effective concentration to amastigotes (EC50ama and EC90ama), and selectivity indexes (SI) were calculated. Lipophilicity (LogP) and mitochondrial membrane potential (ΔΨ) were analyzed. DL21 showed a significant anti-promastigote (EC50pro: 4.68 µM) and anti-amastigote (EC50ama and EC90ama: 0.42 and 15.91 µM, respectively) activity, and substantial SI (94.73) to amastigotes and an adequate Log P (5.54), while not changing ΔΨ. DL21 is a promising drug candidate and further studies are necessary for better understanding licarin A mechanisms of action.