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https://hdl.handle.net/1959.11/22967
Title: | Inhibition of Carbonic Anhydrases with Glycosyltriazole Benzene Sulfonamides | Contributor(s): | Wilkinson, Brendan (author)![]() |
Publication Date: | 2008 | DOI: | 10.1021/jm701426t | Handle Link: | https://hdl.handle.net/1959.11/22967 | Abstract: | A library of glycoconjugate benzene sulfonamides have been synthesized and investigated for their ability to inhibit the enzymatic activity of physiologically relevant human carbonic anhydrase (hCA) isozymes: hCA I, II, and tumor-associated IX. Our synthetic strategy directly links the known CA pharmacophore (ArSO2NH2) to a sugar 'tail' moiety through a rigid 1,2,3-triazole linker unit using the Cu(I)-catalyzed 1,3-dipolar cycloaddition reaction or 'click chemistry'. Many of the glycoconjugates were potent CA inhibitors and exhibited some isozyme selectivity. In particular, the methyl-D-glucuronate triazoles 6 and 14 were potent inhibitors of hCA IX (Kis 9.9 and 8.4 nM, respectively) with selectivity also favoring this isozyme. Other exceptional compounds included the deprotected B-D-ribofuranosyl triazole 15 and α-D-mannosyl triazole 17, which were potent and selective hCA II inhibitors (Ki 7.5 nM and Ki 2.3 nM, respectively). Collectively, the results confirm that modification of ring size, stereochemical configuration, and chain length in the sugar tail moiety of glycoconjugate CA inhibitors permits tunable potency and selectivity that may constitute an important avenue for the future development of efficacious and selective CA-based therapeutics. | Publication Type: | Journal Article | Source of Publication: | Journal of Medicinal Chemistry, 51(6), p. 1945-1953 | Publisher: | American Chemical Society | Place of Publication: | United States of America | ISSN: | 1520-4804 0022-2623 |
Fields of Research (FoR) 2008: | 030401 Biologically Active Molecules 030503 Organic Chemical Synthesis 030499 Medicinal and Biomolecular Chemistry not elsewhere classified |
Fields of Research (FoR) 2020: | 340401 Biologically active molecules 340499 Medicinal and biomolecular chemistry not elsewhere classified 340503 Organic chemical synthesis |
Socio-Economic Objective (SEO) 2008: | 970103 Expanding Knowledge in the Chemical Sciences 929999 Health not elsewhere classified 970106 Expanding Knowledge in the Biological Sciences |
Socio-Economic Objective (SEO) 2020: | 280102 Expanding knowledge in the biological sciences 200199 Clinical health not elsewhere classified 280105 Expanding knowledge in the chemical sciences |
Peer Reviewed: | Yes | HERDC Category Description: | C1 Refereed Article in a Scholarly Journal |
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Appears in Collections: | Journal Article School of Science and Technology |
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