In situ click synthesis of glycosyltriazole arylsulfonamides: Hydrophilic carbonic anhydrase II inhibitors.
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The Carbonic anhydrase (CA) family of hydrolytic Zn(II) metalloenzymes are ubiquitous to all eukaryotic and prokaryotic cells. For decades, aryl sulfonamides have been a mainstay of clinical intervention as antibacterial agents, but only more recently have sulfonamide CA inhibitors been investigated for their anti-cancer and anti-glaucoma activities.[1,2] Recently, Supuran and coworkers have synthesized and evaluated the activity of a series of ߭glycosyl sulfonamides as topical anti-glaucoma agents in rabbit models with high intra ocular pressures (IOP). Within this study, we have developed a new class of hydrophilic aryl sulfonamides with potential anti-glaucoma activity using the in situ click chemistry approach. Screening of the library was achieved using a flouresent DNSA assay, as well as in situ in the presence of the enzyme using a bioaffinity characterization mass spectrometry (BACMS) methodology. Inhibition constants (Ki's) were found to be in the mid to low nM range for bCAII, comparable to the in vitro activity of current treatments of glaucoma.
Abstracts of Papers, 231st ACS National Meeting, Atlanta, GA, United States, March 26-30, 2006.