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-dimethylthiazol-2-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 (EC_50ama and EC_90ama), and selectivity indexes (SI) were calculated. Lipophilicity (LogP) and mitochondrial membrane potential (∆Ψ) were analyzed. DL21 showed a significant anti-promastigote (EC_50pro: 4.68 μM) and anti-amastigote (EC_50ama and EC_90ama: 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 ∆Ψ. DL21 is a promising drug candidate and further studies are necessary for better understanding licarin A mechanisms of action.

Keywords:
leishmaniasis; new drugs; derivatives; licarin A