Antiproliferative activity of the Michael adducts of aroylacrylic acids and cyclic amines
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Antiproliferative activity of twenty one Michael adducts of aroylacrylic acids and cyclic amines ( N -Me-piperazine, imidazole, 2-Me-imidazole, and indole) was tested toward five human tumor cell lines (HeLa, LS174, K562, FemX, MDA-MB-361) in vitro. Compounds exerted antiproliferative activity in the high to the single-digit micromolar concentrations, causing increase of the cell population fraction in S phase and apoptosis. N -Me-piperazine and imidazole derivatives of aroylacrylic acids substituted with bulky alkyl substituents (2,4-di- i -Pr-Ph-, 2,4,6-tri-Et-Ph-, or β -tetrahydronaphthyl-) showed the best potency, while indole adducts were proved as the inferior antiproliferative agents. Few compounds showed significant selectivity, tumor versus healthy cells, with selectivity index ∼60 for the most selective congener. An unbiased in silico distinction between more and less potent compounds was obtained from 3D QSAR models derived by alignment-independent GRIND-2 descripto...rs.
Keywords:Antiproliferative activity / Selectivity / Michael adducts / Aroylacrylic acids / 3D QSAR
Source:Molecular Diversity, 2014, 18, 3, 577-592