The cytotoxic activity of synthetic progestins (pregna-D'-pentaranes) II-V full agonists of the progesterone receptor (PR) for PR-positive and PR-negative cells of human breast carcinoma was studied. These compounds were more active in the PR-positive MCF-7 cells than in the PR-negative MDA-MB-453 cells. Cytotoxic effects of tested compounds against normal epithelial MDCK cells were not found. Molecular modeling of studied steroids with PR showed that all progestins with close energy values can bind to the ligand binding domain (LBD) of PR and the magnitude of the energy exceeds the value estimated for the progesterone molecule. Thus, the studied progestins are active against different molecular subtypes of breast cancer and represent a promising class of chemical compounds for oncology.
Izuchena tsitotoksicheskaia aktivnost' sinteticheskikh progestinov – polnykh agonistov retseptora progesterona (RP) – riada pregna-D'-pentaranov II-V na RP-pozitivnykh i RP-negativnykh kletkakh kartsinomy molochnoĭ zhelezy cheloveka (RMZh). Obnaruzhena bolee vysokaia aktivnost' analiziruemykh soedineniĭ v RP-pozitivnykh kletkakh MCF-7, chem v negativnykh kletkakh MDA-MB-453. Tsitotoksicheskikh éffektov v kletkakh normal'nogo épiteliia MDCK pri obrabotke issleduemymi soedineniiami vyiavleno ne bylo. Molekuliarnoe modelirovanie izuchennykh steroidov s RP pokazalo, chto vse progestiny s blizkimi znacheniiami énergiĭ mogut vzaimodeĭstvovat' s ligand-sviazyvaiushchim (LS) domenom retseptora i velichiny étikh énergiĭ prevyshaiut znachenie, otsenennoe dlia molekuly progesterona. Takim obrazom, izuchennye progestiny proiavliaiut aktivnost' v otnoshenii razlichnykh podtipov kletok RMZh i iavliaiutsia perspektivnym klassom khimicheskikh soedineniĭ v onkologii.
Keywords: cytotoxic activity; molecular modeling; pentaranes; progesterone receptor.