Catalytic cyclometallation in steroid chemistry VI: Targeted synthesis of hybrid molecules based on steroids and tetradeca-5Z,9Z-diene-1,14-dicarboxylic acid and study of their antitumor activity

[Display omitted] •Synthesis of steroid containing 5Z,9Z-dienoic acids have been developed.•New molecules are efficient apoptosis inducers in cancer cells.•The structures of all novel compounds were confirmed by NMR measurements. Hybrid molecules based on a number of steroids (cholesterol, pregnenolone, androsterone) and 1,14-tetradeca-5Z,9Z-dienedicarboxylic acid linked via mono- and diethylene glycol spacers were synthesized for the first time and studied for antitumor activity in vitro. The acid was prepared using catalytic cyclomagnesiation of oxygenated 1,2-dienes with Grignard reagent in the presence of Cp2TiCl2 as the key synthetic step. Using flow cytometry, the new molecules were shown for the first time to be efficient apoptosis inducers in the HeLa, Hek293, U937, Jurkat, and K562 cell cultures and to have dose-dependent effect on the S and G2 phases of the cell cycle.