New sulfonamide-based glycosides incorporated 1,2,3-triazole as cytotoxic agents through VEGFR-2 and carbonic anhydrase inhibitory activity

• Published in: Scientific reports 2024-06, Vol.14 (1), p.13028-16
• Main Authors: Abbas, Hebat-Allah S., Nossier, Eman S., El-Manawaty, May A., El-Bayaa, Mohamed N.
• Format: Article
• Language: English
• Subjects: 1,2,3-Triazole; 631/67; 639/638; 639/638/403; Antigens, Neoplasm - metabolism; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Antiproliferative; Cancer; Carbonic anhydrase; Carbonic Anhydrase Inhibitors - chemistry; Carbonic Anhydrase Inhibitors - pharmacology; Carbonic Anhydrase IX - antagonists & inhibitors; Carbonic Anhydrase IX - metabolism; Carbonic anhydrases; Carbonic Anhydrases - chemistry; Carbonic Anhydrases - metabolism; Cell Line, Tumor; Copper; Cytotoxic agents; Cytotoxicity; Doxorubicin; Glycosides; Glycosides - chemistry; Glycosides - pharmacology; Hep G2 Cells; Humanities and Social Sciences; Humans; Hybrids; Isoforms; MCF-7 Cells; Molecular Docking Simulation; multidisciplinary; Science; Science (multidisciplinary); Structure-Activity Relationship; Sulfonamide-based; Sulfonamides; Sulfonamides - chemistry; Sulfonamides - pharmacology; Triazoles; Triazoles - chemistry; Triazoles - pharmacology; Tumor cell lines; Vascular Endothelial Growth Factor Receptor-2 - antagonists & inhibitors; Vascular Endothelial Growth Factor Receptor-2 - metabolism; Vascular endothelial growth factor receptors; VEGFR-2
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-024-62864-9

New sulfonamide-triazole-glycoside hybrids derivatives were designed, synthesised, and investigated for anticancer efficacy. The target glycosides’ cytotoxic activity was studied with a panel of human cancer cell lines. Sulfonamide-based derivatives, 4 , 7 and 9 exhibited promising activity against HepG-2 and MCF-7 (IC 50  = 8.39–16.90 μM against HepG-2 and 19.57–21.15 μM against MCF-7) comparing with doxorubicin (IC 50  = 13.76 ± 0.45, 17.44 ± 0.46 μM against HepG-2 and MCF-7, rescpectively). To detect the probable action mechanism, the inhibitory activity of these targets was studied against VEGFR-2, carbonic anhydrase isoforms hCA IX and hCA XII. Compoumds 7 and 9 gave favorable potency (IC 50  = 1.33, 0.38 μM against VEGFR-2, 66, 40 nM against hCA IX and 7.6, 3.2 nM against hCA XII, respectively), comparing with sorafenib and SLC-0111 (IC 50  = 0.43 μM, 53 and 4.8 nM, respectively). Moreover, the docking simulation was assessed to supply better rationalization and gain insight into the binding affinity between the promising derivatives and their targeted enzymes that was used for further modification in the anticancer field.