Synthesis and biological evaluation of polyalthic acid derivatives for the treatment of neglected diseases.

Polyalthic acid is a naturally occurring diterpene found in copaiba oil, one of the most popular natural medicines in the Amazon. Based on the reported antileishmanial activity of copaiba oil, a series of amides and diols derivatives of polyalthic acid were synthesized and tested against Leishmania donovani and Trypanosoma brucei. Polyalthic acid was active in both assays with IC50 ranging from 3.87 to 8.68 μg/mL. The compound with best antileishmanial activity was 2 h (IC50=3.84 μg/mL) and compound 2c showed the best antitrypanosomal activity with an IC50 of 2.54 μg/mL.