Structure-activity relationship of antileishmanials neolignan analogues

Twenty-two synthetic analogues of neolignans comprising beta-ketoethers and beta-ketosulfides were obtained from condensation reactions among beta-bromoketones and phenols or thiophenols, respectively, in basic solutions, and assayed in vitro for activity against intracellular Leishmania amazonensis and Leishmania donovani amastigotes, the causative agents of cutaneous and visceral leishmaniasis. The highest selective activity was found for compounds with sulfur bridges, whereas beta-ketosulphoxides and beta-ketosulphones had significantly less growth inhibitory activity. Compounds 2-[(4-chlorophenyl)thio]propan-1-one and 1-(3,4-dimethoxy)2-[(4-methylphenyl)thio]propan-1-one were the most potent, inhibiting the growth parasite species by over 90% at microgram/mL, but only compound 1-(3,4-dimethoxy)-2-[(4-methylphenyl)thio]propan-1-one was selectively toxic to the parasites. (C) 2007 Elsevier Ltd. All rights reserved.