Design of Sulfonamide-Based Glycosides Incorporated with 1,2,3-Triazole Scaffold as Potential VEGFR-2 and Carbonic Anhydrase Inhibitors: Synthesis, Cytotoxic Activity and In Silico Studies

Abstract

The current study reports new sulfonamide-triazole-glycoside hybrids' design, synthesis, and anticancer activity. The target glycosides' cytotoxic activity was studied with a panel of human cancer cell lines. Azido sulfonamide compound 4 exhibited moderate activity against A-549 and HCT-116 and excellent potency against HepG-2 and MCF-7. Replacement of the azido group with 1,2,3-triazole- glycoside hybrids in 6-13 afforded variable activities against tested cell lines ranging from weak to excellent ones in acetylated glycosides 6-9. On the other hand, hydroxylated glycosides 10-13, revealed weak cytotoxicity except N-cyclohexylbenzene derivatives 11, 13 expressing promising activity against HepG-2. In addition, the hydroxylated glycoside 13 gave moderate activity against MCF-7. To detect the probable action mechanism, the inhibitory activity of the promising sulfonamide-triazole-glycoside hybrids was studied against VEGFR-2, carbonic anhydrase isoforms hCA IX and hCA XII. Moreover, the docking evaluation was simulated to supply better rationalization and gain insight into the binding affinity between their targeted enzymes and the promising derivatives and used for further modification in the anticancer field.