Leishmanicidal effect of derivatives of dibenzylbutirolactonic lignans from Piper cubeba

Leishmaniasis is an infection characterized for being a parasitic disease with great incidence in the world. Recent publications have highlighted numerous biological activities attributed to the dibenzylbutirolactonic lignan (-)-cubebin (1). Ongoing studies have focused on its structural optimization, in order to obtain derivatives with greater pharmacological potential, low costs and low toxicity. The aim of this study was the obtainment of (1), its semisynthetic derivatives and the evaluation of their leishmanicidal activity. From the extract of seeds of P. cubeba was obtained (1), and it was used for the synthesis of: (-)-O-benzylcubebin (2), (-)-O-methylcubebin (3), (-)-O-(N,N-dimethylamino-ethyl)-cubebin (4) and (-)-O-acethylcubebin (5). The in vitro biological activity of the lignans against Leishmania amazonensis promastigote forms was carried out with MTT method. It could be verified that (2), (3) and (4) showed leishmanicidal potential (61,6%, 56,9%, 66,3%, respectively), as these effects were comparable to those observed for positive control, Amphotericin, at 12,5µM (76,4%). The cytotoxicity assay showed that the in vitro activity of the compounds may not be related to cytotoxic effects, since they don't present significant cytotoxicity (IC₅₀: 328,2; 383,3; 355,7; 323,1;370,4µM, respectively). Sponsors: FAPESP, CNPq and CAPES.