Design and Synthesis of New Agents for Prostate Cancer Treatment Inspired by Steroidal CYP17 A1 Inhibitors

Steroid derivatives modified with nitrogen containing heterocycles attract attention as anticancer agents for prostate cancer treatment. In this study we have developed a simple and convenient procedure for preparation of 17(20)-21-norpregnene and androst-16-ene 2’-oxazolinyl and 2’-benzoxazolyl derivatives, based on the reaction of an appropriately modified steroidal carboxylic acid with 1,2-amino alcohols or o-aminophenol. Using this method we conducted synthesis a series of new steroid hybrids differing either in the structure of steroidal part, or in the structure of nitrogen containing heterocycle (23 compounds in total). Some of compounds revealed high anti-proliferative activity in prostate carcinoma LNCaP and PC-3 cells, exceeding that for well-known agents abiraterone and galeterone. Oxazoline containing derivative of [17(20)]-21-norpregnene potently stimulated apoptosis in DU-145 cells and inhibited the growth of tumors in DU-145 and 22Rv1 derived xenograft models in direct comparison with abiraterone. © 2022 Wiley-VCH GmbH.