Antiproliferative activity of the Michael adducts of aroylacrylic acids and cyclic amines

• Published in: Molecular diversity Vol. 18; no. 3; pp. 577 - 592
• Main Authors: Juranic, Ivan O, Tosic, Ana V, Kolundzija, Branka, Drakulic, Branko J
• Format: Journal Article
• Language: English
• Published: Cham Springer International Publishing 01.08.2014; Springer Nature B.V
• Subjects: Acids; Acrylates - chemistry; Acrylates - pharmacology; Amines - chemistry; Amines - pharmacology; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biochemistry; Biomedical and Life Sciences; Cell Line, Tumor; Cell Proliferation - drug effects; Chemical engineering; Full-Length Paper; Humans; Life Sciences; Models, Molecular; Molecular chemistry; Molecular Conformation; Organic Chemistry; Pharmacy; Polymer Sciences; Michael adducts; 3D QSAR; Selectivity; Antiproliferative activity; Aroylacrylic acids
• ISSN: 1381-1991; 1573-501X
• DOI: 10.1007/s11030-014-9528-4

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. Graphical Abstract