Antileishmanial activity of <i>neo</i>-clerodane diterpenes from <i>Croton echioides</i>

Abstract

Nowadays, new leishmanicidal drugs are needed and natural products arise as a promising alternative source. Therefore, bioguided fractionation of a hydroethanolic extract from the stem bark of <i>Croton echioides</i> Baill. were conducted based on its antileishmanial activity. Two novel <i>neo</i>-clerodane diterpenoids methyl-15,16-epoxy-3,13(16),14-<i>neo</i>-clerodatrien-17,18-dicarboxylate (<b>1</b>) and dimethyl-3-oxo-15,16-epoxy-13(16),14-<i>neo</i>-clerodadien-17,18-dicarboxylate (<b>2</b>) were isolated, as well as four known compounds (<b>3-6</b>) and lupeol, from the hexane fraction. Their structures were established by NMR analysis. The crude extract, fractions and the compounds (<b>1</b> and <b>3-6</b>) were evaluated for their <i>in vitro</i> antileishmanial activity and cytotoxicity against macrophages J774A.1. The selectivity index (SI) were calculated. The most active compound against promastigote forms of <i>L. amazonensis</i> was the clerodane diterpene <b>4</b>, with IC₅₀ values of 8.3 µM and SI value of 80.9. Our results highlighted stem bark of <i>Croton echioides</i> Baill. as a promising source for the development of a new chemotherapeutic agent to combat leishmaniasis.