A Pregnane Steroid as the Chiral Auxiliary in 1,3‐Dipolar Azomethine Ylide's Cycloaddition: Asymmetric Synthesis and Anticancer Activity of Novel Hybrid Compounds

Abstract

Hybrid chiral molecules containing frameworks of a pregnane steroid and 5‐arylpyrrolidine‐2,4‐dicarboxylate have been synthesized for the first time in a diastereomerically pure form. Chiral pregnane‐based acrylate induced stereoselective formation of all‐cis trisubstituted pyrrolidine moiety under cycloaddition with stabilized N‐metalated azomethine ylides. β‐Dipeptidic fragment was built up at C‐3 pregnane position using consequent acryloylation and stereoselective cycloaddition with stabilized N‐metalated azomethine ylide. All novel hybrid molecules demonstrated micromolar cytotoxic activity against human cervical epithelioid cancer HeLa cell culture in native and estradiol‐stimulated forms and breast carcinoma MCF‐7 cell culture. The most of hybrid compounds are less toxic towards human skin fibroblasts HSF as compared with studied hormonal tumor cells.

The Effects of the Steroids 5-Androstenediol and Dehydroepiandrosterone and Their Synthetic Derivatives on the Viability of K562, HeLa, and Wi-38 Cells and the Luminol-Stimulated Chemiluminescence of Peripheral Blood Mononuclear Cells from Healthy Volunteers

“…Based on the previously obtained data on IC 50 in various cell cultures for steroids with different substituents at the C3 carbon atom of the cyclopentane perhydrophenanthrene ring, which ranged from 7 to 87 μM with 48 h incubation [ 40 , 43 ], we used a fixed concentration of steroids of 10 μM for the primary screening of cytotoxicity.…”