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Molecules. 2018 Nov 30;23(12). pii: E3160. doi: 10.3390/molecules23123160.

Leishmanicidal Activity of Withanolides from Aureliana Fasciculata var. Fasciculata.

Author information

1
Instituto de Pesquisas de Produtos Naturais (IPPN), Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho-Cidade Universitária, 21941-902 Rio de Janeiro, Brazil. smnioe@gmail.com.
2
Laboratório de Bioquímica de Tripanosomatídeos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (FIOCRUZ), 210360-040 Rio de Janeiro, Brazil. juspacheco@hotmail.com.
3
Departamento de Produtos Naturais, Farmanguinhos, Fundação Oswaldo Cruz (FIOCRUZ), 21041-250 Rio de Janeiro, Brazil. andrefarmaciarj@yahoo.com.br.
4
Laboratório de Bioquímica de Tripanosomatídeos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (FIOCRUZ), 210360-040 Rio de Janeiro, Brazil. erpv1994@gmail.com.
5
Faculdade de Educação Tecnológica do Rio de Janeiro (FAETERJ-Rio), 21351-290 Rio de Janeiro, Brazil. ritalafeta@yahoo.com.br.
6
Departamento de Produtos Naturais, Farmanguinhos, Fundação Oswaldo Cruz (FIOCRUZ), 21041-250 Rio de Janeiro, Brazil. mraquelf6@yahoo.com.br.
7
Instituto de Pesquisas de Produtos Naturais (IPPN), Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho-Cidade Universitária, 21941-902 Rio de Janeiro, Brazil. makaplan@nppn.ufrj.br.
8
Laboratório de Bioquímica de Tripanosomatídeos, Instituto Oswaldo Cruz, Fundação Oswaldo Cruz (FIOCRUZ), 210360-040 Rio de Janeiro, Brazil. ects@ioc.fiocruz.br.

Abstract

Leishmaniasis is the generic denomination to the neglected diseases caused by more than 20 species of protozoa belonging to the genus Leishmania. The toxic and parenteral-delivered pentavalent antimonials remain to be the first-line treatment. However, all the current used drugs have restrictions. The species Aureliana fasciculata (Vell.) Sendtner var. fasciculata is a native Brazilian species parsimoniously studied on a chemical point of view. In this study, the antileishmanial activity of A. fasciculata was evaluated. Among the evaluated samples of the leaves, the dichloromethane partition (AFfDi) showed the more pronounced activity, with IC50 1.85 µg/ml against promastigotes of L. amazonensis. From AFfDi, two active withanolides were isolated, the Aurelianolides A and B, with IC50 7.61 μM and 7.94 μM, respectively. The withanolides also proved to be active against the clinically important form, the intracellular amastigote, with IC50 2.25 μM and 6.43 μM 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.

KEYWORDS:

aurelianolides; leishmania; solanaceae; withanolides

PMID:
30513673
PMCID:
PMC6320798
DOI:
10.3390/molecules23123160
[Indexed for MEDLINE]
Free PMC Article

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