Cytotoxic activity and molecular modeling of progestins, pregna-D′-pentaranes

Abstract

The cytotoxic activity of synthetic progestins (pregna-D′-pentaranes II–V), full agonists of the progesterone receptor (PR), has been investigated towards PR-positive and PR-negative cells of human breast carcinoma. These compounds were more active in PR-positive MCF-7 cells than in PR-negative MDA-MB-453 cells. The tested compounds did not demonstrate cytotoxic effects towards normal epithelial MDCK cells. Molecular modeling of studied steroids with PR showed that all progestins with close energy values could bind to the ligand binding domain (LBD) of PR and the magnitude of the energy exceeded the value estimated for the progesterone molecule. Thus, the studied progestins are active towards different molecular subtypes of breast cancer and represent a promising class of chemical compounds for oncology.