Design, synthesis, and carbonic anhydrase inhibition activities of Schiff bases incorporating benzenesulfonamide scaffold: Molecular docking application
In this study, The inhibitory actions of human carbonic anhydrase (CA, EC 4.2.1.1) (hCA) isoforms I, II, IX, and XII are being examined using recently synthesized substituted hydroxyl Schiff derivatives based on the quinazoline scaffold 4–22. Quinazolines 2, 3, 4, 5, 7, 10, 15, and 18 reduce the act...
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2023-12-01
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| Series: | Saudi Pharmaceutical Journal |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S1319016423003614 |
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| author | Adel S. El-Azab Alaa A.-M. Abdel-Aziz Silvia Bua Alessio Nocentini Ahmed H. Bakheit Hamad M. Alkahtani Mohamed M. Hefnawy Claudiu T. Supuran |
| author_facet | Adel S. El-Azab Alaa A.-M. Abdel-Aziz Silvia Bua Alessio Nocentini Ahmed H. Bakheit Hamad M. Alkahtani Mohamed M. Hefnawy Claudiu T. Supuran |
| author_sort | Adel S. El-Azab |
| collection | DOAJ |
| description | In this study, The inhibitory actions of human carbonic anhydrase (CA, EC 4.2.1.1) (hCA) isoforms I, II, IX, and XII are being examined using recently synthesized substituted hydroxyl Schiff derivatives based on the quinazoline scaffold 4–22. Quinazolines 2, 3, 4, 5, 7, 10, 15, and 18 reduce the activity of hCA I isoform effectively to a Ki of 87.6–692.3 nM, which is nearly equivalent to or more potent than that of the standard drug AAZ (Ki, 250.0 nM). Similarly, quinazolines 2, 3, and 5 and quinazoline 14 effectively decrease the inhibitory activity of the hCA II isoform to a KI of 16.9–29.7 nM, comparable to that of AAZ (Ki, 12.0 nM). The hCA IX isoform activity is substantially diminished by quinazolines 2–12 and 14–21 (Ki, 8.9–88.3 nM against AAZ (Ki, 25.0 nM). Further, the activity of the hCA XII isoform is markedly inhibited by the quinazolines 3, 5, 7, 14, and 16 (Ki, 5.4–19.5 nM). Significant selectivity levels are demonstrated for inhibiting tumour-associated isoforms hCA IX over hCAI, for sulfonamide derivatives 6–15 (SI; 10.68–186.29), and 17–22 (SI; 12.52–57.65) compared to AAZ (SI; 10.0). Sulfonamide derivatives 4–22 (SI; 0.50–20.77) demonstrated a unique selectivity in the concurrent inhibition of hCA IX over hCA II compared to AAZ (SI; 0.48). Simultaneously, benzenesulfonamide derivative 14 revealed excellent selectivity for inhibiting hCA XII over hCA I (SI; 60.35), whereas compounds 5–8, 12–14, 16, and 18–22 demonstrated remarkable selectivity for hCA XII inhibitory activity over hCA II (SI; 2.09–7.27) compared to AAZ (SI; 43.86 and 2.10, respectively). Molecular docking studies additionally support 8 to hCA IX and XII binding, thus indicating its potential as a lead compound for inhibitor development. |
| format | Article |
| id | doaj-art-1b543ab78ca8435c914ea8a96d403b3f |
| institution | Kabale University |
| issn | 1319-0164 |
| language | English |
| publishDate | 2023-12-01 |
| publisher | Springer |
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| series | Saudi Pharmaceutical Journal |
| spelling | doaj-art-1b543ab78ca8435c914ea8a96d403b3f2025-08-20T03:54:23ZengSpringerSaudi Pharmaceutical Journal1319-01642023-12-01311210186610.1016/j.jsps.2023.101866Design, synthesis, and carbonic anhydrase inhibition activities of Schiff bases incorporating benzenesulfonamide scaffold: Molecular docking applicationAdel S. El-Azab0Alaa A.-M. Abdel-Aziz1Silvia Bua2Alessio Nocentini3Ahmed H. Bakheit4Hamad M. Alkahtani5Mohamed M. Hefnawy6Claudiu T. Supuran7Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi Arabia; Corresponding authors.Department of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi ArabiaDepartment of Neurofarba, Sezione di Scienze Farmaceutiche Nutraceutiche, Università degli Studi di Firenze, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, ItalyDepartment of Neurofarba, Sezione di Scienze Farmaceutiche Nutraceutiche, Università degli Studi di Firenze, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, ItalyDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi ArabiaDepartment of Pharmaceutical Chemistry, College of Pharmacy, King Saud University, P.O. Box 2457, Riyadh 11451, Saudi ArabiaDepartment of Neurofarba, Sezione di Scienze Farmaceutiche Nutraceutiche, Università degli Studi di Firenze, Via U. Schiff 6, 50019 Sesto Fiorentino, Florence, Italy; Corresponding authors.In this study, The inhibitory actions of human carbonic anhydrase (CA, EC 4.2.1.1) (hCA) isoforms I, II, IX, and XII are being examined using recently synthesized substituted hydroxyl Schiff derivatives based on the quinazoline scaffold 4–22. Quinazolines 2, 3, 4, 5, 7, 10, 15, and 18 reduce the activity of hCA I isoform effectively to a Ki of 87.6–692.3 nM, which is nearly equivalent to or more potent than that of the standard drug AAZ (Ki, 250.0 nM). Similarly, quinazolines 2, 3, and 5 and quinazoline 14 effectively decrease the inhibitory activity of the hCA II isoform to a KI of 16.9–29.7 nM, comparable to that of AAZ (Ki, 12.0 nM). The hCA IX isoform activity is substantially diminished by quinazolines 2–12 and 14–21 (Ki, 8.9–88.3 nM against AAZ (Ki, 25.0 nM). Further, the activity of the hCA XII isoform is markedly inhibited by the quinazolines 3, 5, 7, 14, and 16 (Ki, 5.4–19.5 nM). Significant selectivity levels are demonstrated for inhibiting tumour-associated isoforms hCA IX over hCAI, for sulfonamide derivatives 6–15 (SI; 10.68–186.29), and 17–22 (SI; 12.52–57.65) compared to AAZ (SI; 10.0). Sulfonamide derivatives 4–22 (SI; 0.50–20.77) demonstrated a unique selectivity in the concurrent inhibition of hCA IX over hCA II compared to AAZ (SI; 0.48). Simultaneously, benzenesulfonamide derivative 14 revealed excellent selectivity for inhibiting hCA XII over hCA I (SI; 60.35), whereas compounds 5–8, 12–14, 16, and 18–22 demonstrated remarkable selectivity for hCA XII inhibitory activity over hCA II (SI; 2.09–7.27) compared to AAZ (SI; 43.86 and 2.10, respectively). Molecular docking studies additionally support 8 to hCA IX and XII binding, thus indicating its potential as a lead compound for inhibitor development.http://www.sciencedirect.com/science/article/pii/S1319016423003614MetalloenzymeQuinazolines synthesisHydrazones incorporating ethylsulfonamideCA inhibitorsCA selectivity |
| spellingShingle | Adel S. El-Azab Alaa A.-M. Abdel-Aziz Silvia Bua Alessio Nocentini Ahmed H. Bakheit Hamad M. Alkahtani Mohamed M. Hefnawy Claudiu T. Supuran Design, synthesis, and carbonic anhydrase inhibition activities of Schiff bases incorporating benzenesulfonamide scaffold: Molecular docking application Saudi Pharmaceutical Journal Metalloenzyme Quinazolines synthesis Hydrazones incorporating ethylsulfonamide CA inhibitors CA selectivity |
| title | Design, synthesis, and carbonic anhydrase inhibition activities of Schiff bases incorporating benzenesulfonamide scaffold: Molecular docking application |
| title_full | Design, synthesis, and carbonic anhydrase inhibition activities of Schiff bases incorporating benzenesulfonamide scaffold: Molecular docking application |
| title_fullStr | Design, synthesis, and carbonic anhydrase inhibition activities of Schiff bases incorporating benzenesulfonamide scaffold: Molecular docking application |
| title_full_unstemmed | Design, synthesis, and carbonic anhydrase inhibition activities of Schiff bases incorporating benzenesulfonamide scaffold: Molecular docking application |
| title_short | Design, synthesis, and carbonic anhydrase inhibition activities of Schiff bases incorporating benzenesulfonamide scaffold: Molecular docking application |
| title_sort | design synthesis and carbonic anhydrase inhibition activities of schiff bases incorporating benzenesulfonamide scaffold molecular docking application |
| topic | Metalloenzyme Quinazolines synthesis Hydrazones incorporating ethylsulfonamide CA inhibitors CA selectivity |
| url | http://www.sciencedirect.com/science/article/pii/S1319016423003614 |
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