An efficient and convenient approach for synthesizing norethindrone prodrugs carrying anti-cancerous, anti-inflammatory and anti-asthmatic activity via Pd Catalized Sonogashira Coupling and their simulation studies

Abstract

In the present work novel prodrugs of Norethindrone have been synthesized with the help of sonogashira cross coupling reaction yielding the 17‑hydroxy-13-methyl-17-(phenylethynyl)- 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17-dodecahydro-1H-cyclopenta [a]phenanthren-3(2H)-one, 17‑hydroxy-13-methyl-17-(p-tolylethynyl)- 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17-dodecahydro-1H-cyclopenta [a]phenanthren-3(2H)-one and 4-((17‑hydroxy-13-methyl-3-oxoz 2, 3, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17-tetradecahydro-1H-cyclopenta [a]phenanthren-17-yl)ethynyl)benzaldehyde. The structure of the synthesized compounds were characterized with the help of 1H, 13C NMR, UV, IR and mass spectrometry. Norethindrone is used for contraception and menopausal symptoms. During in silico studies the potential of the ligands 1, 2, 3&4 were evaluated against the different proteins carrying Contraceptive, Anti-inflammatory, Anti-asthmatic and Anti-cancerous properties. Binding energy ranging from -8.51 to -11.49 and increase in the number of hydrogen bonds suggest that the synthesized ligands can play important role as Contraceptive, Anti-inflammatory, Anti-asthmatic as well as Anti-cancerous drugs. In-vitro cytotoxic activity against cervical cancer cell with ligands 2, 3, 4 shows better results as compare to compound 1and compound 4 found to be more potential.