6533b855fe1ef96bd12b08cf
RESEARCH PRODUCT
5-Substituted-benzylsulfanyl-thiophene-2-sulfonamides with effective carbonic anhydrase inhibitory activity: Solution and crystallographic investigations.
Jekaterīna IvanovaDaniela VulloKaspars TarsRaivis ŽAlubovskisClaudiu T. SupuranAndris KazaksJanis LeitansAgnese Balodesubject
Gene isoformModels MolecularStereochemistryClinical BiochemistryPharmaceutical ScienceCrystal structureThiophenesCrystallography X-Ray01 natural sciencesBiochemistryAdductchemistry.chemical_compoundStructure-Activity RelationshipCarbonic anhydraseDrug DiscoveryThiopheneHumansCarbonic Anhydrase InhibitorsMolecular BiologyCarbonic AnhydrasesSulfonamidesbiologyDose-Response Relationship DrugMolecular Structure010405 organic chemistryOrganic ChemistryLyaseTransmembrane protein0104 chemical sciencesSolutions010404 medicinal & biomolecular chemistryCytosolchemistrybiology.proteinMolecular Medicinedescription
Abstract A series of 5-substituted-benzylsulfanyl-thiophene-2-sulfonamides was prepared by reacting 5-bromo-thiophene-2-sulfonamide with 5-substituted-benzyl mercaptans. The new compounds were investigated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors. The cytosolic human (h) isoforms hCA I was poorly inhibited by the new sulfonamides (KIs in the range of 683–4250 nM), whereas hCA II, and the transmembrane, tumor associated isoforms hCA IX and XII were effectively inhibited in the subnanomolar–nanomolar range. A high resolution X-ray crystal structure of the adduct of hCA II with one of the new sulfonamides allowed us to rationalize the excellent inhibitory activity of these heterocyclic sulfonamides.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-02-01 | Bioorganicmedicinal chemistry |