Cytostatic Activity and Ligand-Receptor Interaction Energy of the Novel Russian-Produced Gestagen Gestobutanoil and its Metabolites

With the aim of clarifying the cytostatic effect of the Russian-made gestagen gestobutanoil (17α-acetoxy-3β-hydroxy-6-methylpregna-4,6-dien-20-one butyl ester), which is a member of an original group of transformed gestagens containing an ester substituent in place of the 3-keto group, the cytostatic activities of its metabolites (17α-acetoxy-3β-hydroxy-6-methylpregna-4,6-dien-20-one (AMP-17) and megestrol acetate) and a reference agent (progesterone) were studied in uterine cervical tumor line HeLa. Complex formation by these steroids with progesterone receptor binding sites was evaluated by computer modeling (docking) by determination of the interaction energy of the partner molecules. The cytostatic activity of gestobutanoil was greater than that of reference compound and may be associated with the formation of its active metabolites. Conformations of the gestobutanoil-receptor complex with binding energies significantly different from those of complexes with progesterone, AMP-17, and megestrol acetate were demonstrated; this may be the cause of changes in the affinity of gestobutanoil for progesterone receptors and modulation of its biological activity.