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

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

  • Sci Rep. 2024 Jun 6;14(1):13028. doi: 10.1038/s41598-024-62864-9.
Hebat-Allah S Abbas 1,  Eman S Nossier 2 3,  May A El-Manawaty 4,  Mohamed N El-Bayaa 5 6
Affiliations

Affiliations

  • 1 Department of Photochemistry, National Research Centre, Cairo, 12622, Egypt. hebanrc@yahoo.com.
  • 2 Department of Pharmaceutical Medicinal Chemistry and Drug Design Department, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, 11754, Egypt.
  • 3 The National Committee of Drugs, Academy of Scientific Research and Technology, Cairo, 11516, Egypt.
  • 4 Pharmacognosy Department, Pharmaceutical and Drug Industries Research Institute, National Research Centre, Cairo, 12622, Egypt.
  • 5 Department of Photochemistry, National Research Centre, Cairo, 12622, Egypt.
  • 6 Department of Chemistry, College of Science, Qassim University, 51452, Buraidah, Saudi Arabia.
PMID: 38844493 DOI: 10.1038/s41598-024-62864-9
Abstract

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 (IC50 = 8.39-16.90 μM against HepG-2 and 19.57-21.15 μM against MCF-7) comparing with doxorubicin (IC50 = 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 (IC50 = 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 (IC50 = 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.

Keywords

1,2,3-Triazole; Antiproliferative; Carbonic anhydrase; Copper; Sulfonamide-based; VEGFR-2.

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