Synthesis of lupeol derivatives and their antileishmanial and antitrypanosomal activities

The natural product lupeol 1 was isolated from aerial parts of Vernonia scorpioides with satisfactory yield, which made it viable to be used as starting material in semisynthetic approach. Ten lupeol derivatives 2-11 were prepared by classical procedures. Including, five new esters derivatives 7-11, which were obtained by structural modifications in the isopropylidene fragment. All semisynthetic compounds and lupeol 1-11 were confirmed by H-1 NMR, C-13 NMR and HRMS. Their antiprotozoal activity was evaluated in vitro against L. amazonensis and T. cruzi. Derivative 6 showed the best antitrypanosomal activity (IC50=12.48g/mL) and the lowest cytotoxic derivative (CC50=161.50g/mL). The mechanism of action of the most active derivatives (4, 6 and 11) is not dependent from the enzyme trypanothione reductase.