title: [Cytotoxic activity and molecular modeling of progestins - pregna-D'-pentarans].
abstract: 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.
authors.affiliation: Blokhin Cancer Research Centre, Moscow, Russia.
authors.forename: A M
authors.initials: AM
authors.lastname: Scherbakov
authors.affiliation: Zelinsky Institute of Organic Chemistry Russian Academy of Sciences, Moscow, Russia.
authors.forename: I S
authors.initials: IS
authors.lastname: Levina
authors.affiliation: Zelinsky Institute of Organic Chemistry Russian Academy of Sciences, Moscow, Russia.
authors.forename: L E
authors.initials: LE
authors.lastname: Kulikova
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia; SRI of Physical-Chemical Medicine Federal Medical and Biological Agency, Moscow, Russia.
authors.forename: I V
authors.initials: IV
authors.lastname: Fedyushkina
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: V S
authors.initials: VS
authors.lastname: Skvortsov
authors.affiliation: Institute of Biomedical Chemistry, Moscow, Russia.
authors.forename: A V
authors.initials: AV
authors.lastname: Veselovsky
authors.affiliation: Zelinsky Institute of Organic Chemistry Russian Academy of Sciences, Moscow, Russia.
authors.forename: Y V
authors.initials: YV
authors.lastname: Kuznetsov
authors.affiliation: Zelinsky Institute of Organic Chemistry Russian Academy of Sciences, Moscow, Russia.
authors.forename: I V
authors.initials: IV
authors.lastname: Zavarzin
mesh_terms: D000818:Animals; D004285:Dogs; D006801:Humans; D061986:MCF-7 Cells; D061985:Madin Darby Canine Kidney Cells; D062105:Molecular Docking Simulation; D011372:Progestins / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D011485:Protein Binding; D011980:Receptors, Progesterone / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D011372:Progestins; D011980:Receptors, Progesterone
keywords: cytotoxic activity; molecular modeling; pentaranes; progesterone receptor