Leishmanicidal Activity of a Quinone Methide Triterpenoid from the roots of Senna spectabilis var. excelsa (Fabaceae)

Abstract

From an extract of the roots of <em>Senna spectabilis </em>var. <em>excelsa (Fabaceae)</em>, eight known metabolites including the quinone methide triterpenoid 17-(methoxycarbonyl)-28-<em>nor</em>-isoiguesterin (<strong>1</strong>) and friedelin (<strong>2</strong>), a putative biosynthetic precursor of this class of metabolites, were isolated by applying several chromatographic methods. The structures of the isolated metabolites were established by High Resolution NMR and MS analysis, and confirmed by comparison of their experimental spectroscopic and physical data with those previously reported in the literature. The 2D structure and relative configuration of metabolite <strong>1</strong> were initially determined via analysis of NOESY experiment and confirmed by quantum mechanics-based ¹³C NMR chemical shift calculations. Metabolite <strong>1 </strong>showed a potent leishmanicidal activity against <em>Leishmania amazonensis </em>and <em>L. brazilensis</em>, with the IC₅₀ values 9.6 and 6.3 μM, respectively, comparable with the positive control miltefosine (IC₅₀ values 12.5 and 12.0 μM, respectively), a currently used agent for leishmaniosis treatment. The first example of the occurrence of a quinone methide triterpenoid in species belonging to the Fabaceae family and the first leishmanicidal activity of metabolite <strong>1 </strong>are reported in this paper.