Antitumor activity of newly synthesized oxo and ethylidene derivatives of bile acids and their amides and oxazolines

•Regio- and stereoselective synthesis of bile acid C-7 ethylidene derivatives.•21 bile acid, amide, oxazoline or/and ethylidene derivatives were prepared.•Antiproliferative activity of compounds was tested against tumor cell lines.•Strong antitumor activity of derivatives against MDA-MB-231, PC3 or HeLa cell lines.

Bile acid derivatives with modifications in side chain and modifications on steroid skeleton were synthetized and their antitumor activity against five human cancer cell lines was investigated. Modifications in side chain include amid group, formed in reaction with 2-amino-2-methylpropanol, and 4,4-dimethyloxazoline group, obtained after cyclization of amides. In the steroid skeleton oxo groups were introduced in position 7 (2, 2a, 2b) and 7,12 (3, 3a, 3b). Ethylidene groups were introduced regio- and stereoselectively on C-7, and/or without stereoselectivity on C-3 by Wittig reaction. By combination of these modifications, a series of 19 bile acid derivatives were synthesized. Compounds containing both C-7 ethylidene and C-12 carbonyl groups (6, 6a, 6b) shown very good antitumor activity with IC50 < 5 µM. Altering carboxylic group to amide or oxazoline group has positive effect on cytotoxicity. Different molecular descriptors were determined in silico and after principal component analysis was found that molecular descriptor BLTF96 can be used for fast assessment of experimental cytotoxicity of bile acid derivatives.