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https://locus.ufv.br//handle/123456789/18272
Tipo: | Artigo |
Título: | Leishmanicidal and cytotoxic activity of hederagenin-bistriazolyl derivatives |
Autor(es): | Rodríguez-Hernández, Diego Barbosa, Luiz C.A. Demuner, Antonio J. Nain-Perez, Amalyn Ferreira, Sebastião R. Fujiwara, Ricardo T. Almeida, Raquel M. de Heller, Lucie Csuk, René |
Abstract: | Aiming to obtain new potent leishmanicidal and cytotoxic compounds from natural sources, the triterpene hederagenin was converted into several new 1,2,3-triazolyl derivatives tethered at C-23 and C-28. For this work hederagenin was isolated from fruits of Sapindus saponaria and reacted with propargyl bromide to afford as a major product bis-propargylic derivative 1 in 74%. Submitting this compound to Huisgen 1,3-dipolar cycloaddition reactions with several azides afforded the derivatives 2–19 with yields in the range of 40–87%. All compounds have been screened for in vitro cytotoxic activity in a panel of five human cancer cell lines by a SRB assay. The bioassays showed that compound 19 was the most cytotoxic against all human cancer cell lines with EC50 = 7.4–12.1 μM. Moreover, leishmanicidal activity was evaluated through the in vitro effect in the growth of Leishmania infantum, and derivatives 1, 2, 5 and 17 were highly effective preventing proliferation of intracellular amastigote forms of L. infantum (IC50 = 28.8, 25.9, 5.6 and 7.4 μM, respectively). All these compounds showed a higher selectivity index and low toxicity against two strains of kidney BGM and liver HepG2 cells. Compound 5 has higher selectivity (1780 times) in comparison with the commercial antimony drug and is around 8 times more selective than the most active compound previously reported hederagenin derivative. Such high activity associated with low toxicities make the new bis-traiazolyl derivatives promising candidates for the treatment of leishmaniasis. In addition, hederagenin and some derivatives (2, 5 and 17) showed interaction in the binding site of the enzyme CYP51Li. |
Palavras-chave: | Hederagenin Triazol Leishmania infantum Cytotoxicity CYP51Li |
Editor: | European Journal of Medicinal Chemistry |
Tipo de Acesso: | Elsevier Masson SAS |
URI: | https://doi.org/10.1016/j.ejmech.2017.09.045 http://www.locus.ufv.br/handle/123456789/18272 |
Data do documento: | 22-Set-2017 |
Aparece nas coleções: | Artigos |
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artigo.pdf Until 2100-12-31 | Texto completo | 928,76 kB | Adobe PDF | Visualizar/Abrir ACESSO RESTRITO |
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