This article describes the synthesis of some novel sulfonamides having the biologically active, thi-azole 4-6, 8, 10-12a,b, 20, 22, 34, 35, imidazo[1,2-a]pyridine 14, imidazo[2,1-c][1,2,4]triazole 15, imidazo[2,1-b]th...This article describes the synthesis of some novel sulfonamides having the biologically active, thi-azole 4-6, 8, 10-12a,b, 20, 22, 34, 35, imidazo[1,2-a]pyridine 14, imidazo[2,1-c][1,2,4]triazole 15, imidazo[2,1-b]thiazole 23, 24, 33, nicotinonitrile 25, 1,3,4-thiadiazine 27, quinoxaline 30 and 1,4-thiazine 31 moieties, starting with 1-(4-(pyrrolidin-1-ylsulfonyl)phenyl)ethanone (1). The structures of the newly synthesized compounds were confirmed by elemental analysis, IR, 1H NMR, 13C NMR and Ms spectral data. All the compounds were tested in-vitro antihuman liver hepatocellular carcinoma cell line (HepG2). Compounds 8, 11, 4, 22, 12a, 33, 35, 27 and 24 with selectivity index (SI) values of 33.21, 30.49, 19.43, 14.82, 10.29, 7.3, 6.87, 6.15 and 4.62, respectively, exhibited better activity than methotrexate (MTX) as a reference drug with SI value of 4.14. Molecular Operating Environment (MOE) performed virtual screening using molecular docking studies of the synthesized compounds. The results indicated that some synthesized compounds are suitable inhibitors against dihydrofolate reductase (DHFR) enzyme (PDB ID: 4DFR) with further modification.展开更多
文摘This article describes the synthesis of some novel sulfonamides having the biologically active, thi-azole 4-6, 8, 10-12a,b, 20, 22, 34, 35, imidazo[1,2-a]pyridine 14, imidazo[2,1-c][1,2,4]triazole 15, imidazo[2,1-b]thiazole 23, 24, 33, nicotinonitrile 25, 1,3,4-thiadiazine 27, quinoxaline 30 and 1,4-thiazine 31 moieties, starting with 1-(4-(pyrrolidin-1-ylsulfonyl)phenyl)ethanone (1). The structures of the newly synthesized compounds were confirmed by elemental analysis, IR, 1H NMR, 13C NMR and Ms spectral data. All the compounds were tested in-vitro antihuman liver hepatocellular carcinoma cell line (HepG2). Compounds 8, 11, 4, 22, 12a, 33, 35, 27 and 24 with selectivity index (SI) values of 33.21, 30.49, 19.43, 14.82, 10.29, 7.3, 6.87, 6.15 and 4.62, respectively, exhibited better activity than methotrexate (MTX) as a reference drug with SI value of 4.14. Molecular Operating Environment (MOE) performed virtual screening using molecular docking studies of the synthesized compounds. The results indicated that some synthesized compounds are suitable inhibitors against dihydrofolate reductase (DHFR) enzyme (PDB ID: 4DFR) with further modification.
