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

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 (Delta psi) were analyzed. DL21 showed a significant anti-promastigote (EC50pro: 4.68 mu M) and anti-amastigote (EC50ama and EC90ama: 0.42 and 15.91 mu M, respectively) activity, and substantial SI (94.73) to amastigotes and an adequate Log P (5.54), while not changing Delta psi. DL21 is a promising drug candidate and further studies are necessary for better understanding licarin A mechanisms of action.