Leishmanicidal Activity of Withanolides from <i>Aureliana Fasciculata</i> var. <i>Fasciculata</i>

• Main Authors: Simone Cristina de M. Lima, Juliana da Silva Pacheco, André M. Marques, Eduardo Raul Pereira Veltri, Rita de Cássia Almeida-Lafetá, Maria Raquel Figueiredo, Maria Auxiliadora Coelho Kaplan, Eduardo Caio Torres-Santos
• Format: Article
• Language: English
• Published: MDPI AG 2018-11-01
• Series: Molecules
• Subjects: leishmania; solanaceae; withanolides; aurelianolides
• Online Access: https://www.mdpi.com/1420-3049/23/12/3160

Leishmaniasis is the generic denomination to the neglected diseases caused by more than 20 species of protozoa belonging to the genus <i>Leishmania</i>. The toxic and parenteral-delivered pentavalent antimonials remain to be the first-line treatment. However, all the current used drugs have restrictions. The species <i>Aureliana fasciculata</i> (Vell.) Sendtner var. <i>fasciculata</i> is a native Brazilian species parsimoniously studied on a chemical point of view. In this study, the antileishmanial activity of <i>A. fasciculata</i> was evaluated. Among the evaluated samples of the leaves, the dichloromethane partition (AFfDi) showed the more pronounced activity, with IC₅₀ 1.85 &#181;g/ml against promastigotes of <i>L. amazonensis</i>. From AFfDi, two active withanolides were isolated, the Aurelianolides A and B, with IC₅₀ 7.61 &#956;M and 7.94 &#956;M, respectively. The withanolides also proved to be active against the clinically important form, the intracellular amastigote, with IC₅₀ 2.25 &#956;M and 6.43 &#956;M for Aurelianolides A and B, respectively. Furthermore, withanolides showed results for in silico parameters of absorption, distribution, metabolism, excretion, and toxicity (ADMET) similar to miltefosine, the reference drug, and were predicted as good oral drugs, with the advantage of not being hepatotoxic. These results suggest that these compounds can be useful as scaffolds for planning drug design.