Single‐Step Synthesis, Characterization, Molecular Docking Studies and In Vitro Analysis of Norethindrone Conjugates

Abstract

In the present work (17‐ethynyl‐13‐methyl‐3‐oxo‐2, 3, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17‐tetradecahydro‐1H‐cyclopenta[a]phenanthren‐17‐yl‐ethyl‐7‐methyl‐4‐oxo‐1,4‐dihydro‐1,8‐naphthyridine‐3‐carboxylate)and (17‐ethynyl‐13‐methyl‐3‐oxo‐2, 3, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17‐tetradecahydro‐1H‐cyclopenta[a]phenanthren‐17‐yl 2‐(4‐chlorophenoxy) acetate), anovel prodrugs of norethindrone have been synthesized. The structure of the synthesized compounds were characterized with the help of 1H, 13C NMR, UV, and IR spectroscopy.Norethindrone is used for contraception or hormone‐related conditions such as endometriosis and menopausal symptoms and to treat bacterial infections in a variety of pharmaceutical formulations. Molecular docking studies of the synthesized compounds explained the most probable interaction pattern with cyclooxygenase‐2 (1CX2),human estrogen receptor (2OCF) and RSK‐4N‐terminal kinase(6G77). Compound 2 & 3 possessedanti‐inflammatoryand cytotoxic activity besides contraceptive. Both thesynthesized compounds were found to be more potent than norethindrone as revealed from the binding energy and in‐vitro cytotoxic activity against lung cancer cells. Anti‐inflammatory and cytotoxic activity for norethindrone is reported for the first time.