Sulfonamide linked neoglycoconjugates--a new class of inhibitors for cancer-associated carbonic anhydrases.
Article Details
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Lopez M, Bornaghi LF, Innocenti A, Vullo D, Charman SA, Supuran CT, Poulsen SA
Sulfonamide linked neoglycoconjugates--a new class of inhibitors for cancer-associated carbonic anhydrases.
J Med Chem. 2010 Apr 8;53(7):2913-26. doi: 10.1021/jm901888x.
- PubMed ID
- 20201556 [ View in PubMed]
- Abstract
The contribution of membrane-bound carbonic anhydrases (CAs) to hypoxic tumor growth and progression in cancer implicates cancer-associated CAs as a promising drug target for oncology. In this paper, we present a new class of sulfonamide-linked neoglycoconjugate that was designed to selectively target and inhibit the extracellular domains of the cancer-relevant CA isozymes. We describe the application of novel, yet straightforward, chemistry toward the synthesis of inhibitors that comprise both S-glycosyl sulfenamides and S-glycosyl sulfonamides. We also present the CA inhibition profile of our new neoglycoconjugates, more specifically a library of 30 compounds (3-32) that were designed to optimize both SAR (structure-activity relationship) and SPR (structure-property relationship) characteristics. We show that our approach produces neutral, water-soluble, and potent inhibitors (K(i)s in the low nanomolar range) that target cancer-associated CAs.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) 4-(2-AMINOETHYL)BENZENESULFONAMIDE Carbonic anhydrase 2 Ki (nM) 160 N/A N/A Details Acetazolamide Carbonic anhydrase 1 Ki (nM) 250 N/A N/A Details Acetazolamide Carbonic anhydrase 12 Ki (nM) 5.7 N/A N/A Details Acetazolamide Carbonic anhydrase 2 Ki (nM) 12 N/A N/A Details Topiramate Carbonic anhydrase 1 Ki (nM) 250 N/A N/A Details Topiramate Carbonic anhydrase 2 Ki (nM) 5 N/A N/A Details