Dillapiole as antileishmanial agent: discovery, cytotoxic activity and preliminary SAR studies of dillapiole analogues.
Arch Pharm (Weinheim)
; 345(12): 934-44, 2012 Dec.
Article
en En
| MEDLINE
| ID: mdl-22996811
ABSTRACT
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 structure-activity relationships (SAR). Compounds were evaluated for in vitro antileishmanial activity and cytotoxic effects on fibroblast cells. Compound 1 presented inhibitory activity against Leishmania amazonensis (IC(50) = 69.3 µM) and Leishmania brasiliensis (IC(50) = 59.4 µM) and induced cytotoxic effects on fibroblast cells mainly in high concentrations. Compounds 2 (IC(50) = 99.9 µM for L. amazonensis and IC(50) = 90.5 µM for L. braziliensis) and 3 (IC(50) = 122.9 µM for L. amazonensis and IC(50) = 109.8 µM 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.
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Tripanocidas
/
Dioxoles
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Compuestos Alílicos
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Descubrimiento de Drogas
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Leishmania
Límite:
Animals
Idioma:
En
Revista:
Arch Pharm (Weinheim)
Año:
2012
Tipo del documento:
Article
País de afiliación:
Brasil