Design, synthesis and antileishmanial in vitro activity of new series of chalcones-like compounds: A molecular hybridization approach

Abstract

AbstractThe chalcone-like series 1a–1g was efficiently synthesized from Morita–Baylis–Hillman reaction (52–74% yields). Compounds 1a–1g were designed by molecular hybridization based on the anti-inflammatory drug methyl salicylate (3) and the antileishmanial moiety of the Morita–Baylis–Hillman adducts 2a–2g. The 1a–1g compounds were much more actives than precursor series 2a–2g, for example, IC50=7.65μM on Leishmania amazonensis and 10.14μM on Leishmania chagasi (compound 1c) when compared to IC50=50.08μM on L. amazonensis and 82.29μM on L. chagasi (compound 2c). The IC50 values of compound 3 (228.49μM on L. amazonensis and 261.45μM on L. chagasi) and acryloyl salicylate 4 (108.50μM on L. amazonensis and 118.83μM on L. chagasi) were determined here, by the first time, on Leishmania