hashem, H. (2024). Design, synthesis, and molecular docking of novel urea linked 1,2,3-triazole-benzenesulfonamide hybrid as potential carbonic anhydrase inhibitors. Journal of Advanced Biomedical and Pharmaceutical Sciences, 7(1), 53-59. doi: 10.21608/jabps.2023.243204.1206
hamada H.H hashem. "Design, synthesis, and molecular docking of novel urea linked 1,2,3-triazole-benzenesulfonamide hybrid as potential carbonic anhydrase inhibitors". Journal of Advanced Biomedical and Pharmaceutical Sciences, 7, 1, 2024, 53-59. doi: 10.21608/jabps.2023.243204.1206
hashem, H. (2024). 'Design, synthesis, and molecular docking of novel urea linked 1,2,3-triazole-benzenesulfonamide hybrid as potential carbonic anhydrase inhibitors', Journal of Advanced Biomedical and Pharmaceutical Sciences, 7(1), pp. 53-59. doi: 10.21608/jabps.2023.243204.1206
hashem, H. Design, synthesis, and molecular docking of novel urea linked 1,2,3-triazole-benzenesulfonamide hybrid as potential carbonic anhydrase inhibitors. Journal of Advanced Biomedical and Pharmaceutical Sciences, 2024; 7(1): 53-59. doi: 10.21608/jabps.2023.243204.1206
Design, synthesis, and molecular docking of novel urea linked 1,2,3-triazole-benzenesulfonamide hybrid as potential carbonic anhydrase inhibitors
Solid tumors often exhibit hypoxia, a condition resulting from rapid tumor growth that outpaces oxygen supply. This hypoxic environment promotes angiogenesis and enhances tumor survival while reducing the effectiveness of anticancer drugs. SLC-0111, a specific inhibitor of human carbonic anhydrase (hCA) IX, is currently being investigated in clinical trials as a potential therapeutic option for hypoxic malignancies. In this study, we describe the synthesis of a novel compound analogue to SLC-0111 by replacing the para-fluorophenyl tail with a phenyl triazole motif. Our aim is to investigate the potential of this new compound as an inhibitor of the cancer-associated hCA IX and hCA XII isoforms. Molecular docking was performed on compound 6 to elucidate its possible binding interactions within the active sites of target enzymes. The hybrid compound exhibited strong binding affinity towards hCA IX and hCA XII isoforms, with higher binding free energy (DG) values (-6.9682 to -5.5453 Kcal/mole) compared to the co-crystallized ligands (-6.9682 to -5.1109 Kcal/mole), respectively. Docking analysis revealed that the sulfonamide moiety fits well within the active sites of target enzymes, interacting with the Zn2+ ion, while the phenyl triazole tail forms hydrophilic and hydrophobic interactions with amino acid residues. These findings suggest that the target compound may exhibit selectivity to inhibit hCA IX and hCA XII isoforms.
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