Dillapiole as Antileishmanial Agent: Discovery, Cytotoxic Activity and Preliminary SAR Studies of Dillapiole Analogues

• DOI: 10.1002/ardp.201200212
• Publication Date: 2012-09-19T12:45:08Z
• Authors: Roberto Parise‐Filho; Kerly Fernanda Me...; Fátima Maria Mott...; Adilson Kleber Fe...; Bárbara Athayde V...; Mariana Celestina...; Maurício Temotheo...; Ricardo Alexandre...; Aline Vivian Vatt...; Michelle Carneiro...; Carlos Alberto Br...
• Keywords: Structure–activity relationship; Leishmania braziliensis; IC50; Phenylpropanoid

Abstract In this paper, the isolation of dillapiole ( 1 ) from Piper aduncum was reported as well semi‐synthesis two phenylpropanoid derivatives [di‐hydrodillapiole 2 ), isodillapiole 3 )], via reduction and isomerization reactions. Also, compounds' molecular properties (structural, electronic, hydrophobic, steric) were calculated investigated to establish some preliminary structure–activity relationships (SAR). Compounds evaluated for in vitro antileishmanial activity cytotoxic effects on fibroblast cells. Compound presented inhibitory against Leishmania amazonensis (IC 50 = 69.3 µM) brasiliensis 59.4 induced cells mainly high concentrations. 99.9 µM L. IC 90.5 braziliensis 122.9 109.8 less active than ). Regarding properties, conformational arrangement side chain, electronic features, hydrophilic/hydrophobic balance seem be relevant explaining its analogues.