Synthesis of lupeol derivatives and their antileishmanial and antitrypanosomal activities

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