title: Antiproliferative activity of the Michael adducts of aroylacrylic acids and cyclic amines.
abstract: 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 descriptors.
authors.affiliation: Department of Chemistry - IChTM, University of Belgrade, Njegoševa 12, 11000 , Belgrade, Serbia.
authors.forename: Ivan O
authors.initials: IO
authors.lastname: Juranić
authors.forename: Ana V
authors.initials: AV
authors.lastname: Tošić
authors.forename: Branka
authors.initials: B
authors.lastname: Kolundžija
authors.forename: Branko J
authors.initials: BJ
authors.lastname: Drakulić
mesh_terms: D000179:Acrylates / Q000737:chemistry* / Q000494:pharmacology*; D000588:Amines / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation
chemical_list: D000179:Acrylates; D000588:Amines; D000970:Antineoplastic Agents; C036658:acrylic acid