Dillapiole as Antileishmanial Agent: Discovery, Cytotoxic Activity and Preliminary SAR Studies of Dillapiole Analogues
Contribuinte(s) |
UNIVERSIDADE DE SÃO PAULO |
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Data(s) |
24/10/2013
24/10/2013
2012
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Resumo |
In this paper, the isolation of dillapiole (1) from Piper aduncum was reported as well as the semi-synthesis of two phenylpropanoid derivatives [di-hydrodillapiole (2), isodillapiole (3)], via reduction and isomerization reactions. Also, the compounds' molecular properties (structural, electronic, hydrophobic, and steric) were calculated and investigated to establish some preliminary structureactivity relationships (SAR). Compounds were evaluated for in vitro antileishmanial activity and cytotoxic effects on fibroblast cells. Compound 1 presented inhibitory activity against Leishmania amazonensis (IC50?=?69.3 mu M) and Leishmania brasiliensis (IC50?=?59.4 mu M) and induced cytotoxic effects on fibroblast cells mainly in high concentrations. Compounds 2 (IC50?=?99.9 mu M for L. amazonensis and IC50?=?90.5 mu M for L. braziliensis) and 3 (IC50?=?122.9 mu M for L. amazonensis and IC50?=?109.8 mu M for L. brasiliensis) were less active than dillapiole (1). Regarding the molecular properties, the conformational arrangement of the side chain, electronic features, and the hydrophilic/hydrophobic balance seem to be relevant for explaining the antileishmanial activity of dillapiole and its analogues. Mackpesquisa Mackpesquisa |
Identificador |
ARCHIV DER PHARMAZIE, WEINHEIM, v. 345, n. 12, pp. 934-944, DEC, 2012 0365-6233 http://www.producao.usp.br/handle/BDPI/35916 10.1002/ardp.201200212 |
Idioma(s) |
eng |
Publicador |
WILEY-V C H VERLAG GMBH WEINHEIM |
Relação |
ARCHIV DER PHARMAZIE |
Direitos |
closedAccess Copyright WILEY-V C H VERLAG GMBH |
Palavras-Chave | #ANTILEISHMANIAL ACTIVITY #CYTOTOXIC ACTIVITY #DILLAPIOLE #MOLECULAR MODELING #SAR STUDIES #NATURAL-PRODUCTS #PIPER #LEISHMANIASIS #LEAVES #CHEMISTRY #EXTRACT #DENSITY #CHEMISTRY, MEDICINAL #CHEMISTRY, MULTIDISCIPLINARY #PHARMACOLOGY & PHARMACY |
Tipo |
article original article publishedVersion |