6533b872fe1ef96bd12d3b4c
RESEARCH PRODUCT
N-Substituted and ring opened saccharin derivatives selectively inhibit transmembrane, tumor-associated carbonic anhydrases IX and XII.
Fabrizio CartaDaniela VulloClaudiu T. SupuranKaspars TarsJekaterīna IvanovaAndris KazaksJanis LeitansRaivis ŽAlubovskissubject
Gene isoformStereochemistryClinical BiochemistryPharmaceutical Science01 natural sciencesBiochemistrychemistry.chemical_compoundStructure-Activity RelationshipSaccharinAntigens NeoplasmCarbonic anhydraseDrug DiscoveryHumansCarbonic Anhydrase IXCarbonic Anhydrase InhibitorsMolecular BiologyAlkylCarbonic Anhydraseschemistry.chemical_classificationbiologyDose-Response Relationship DrugMolecular Structure010405 organic chemistryArylOrganic ChemistryTransmembrane protein0104 chemical sciences010404 medicinal & biomolecular chemistryCytosolEnzymechemistryBiochemistrybiology.proteinMolecular MedicineSelectivitydescription
A series of N-substituted saccharins incorporating aryl, alkyl and alkynyl moieties, as well as some ring opened derivatives were prepared and investigated as inhibitors of the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). The widespread cytosolic isoforms CA I and II were not inhibited by these sulfonamides whereas transmembrane, tumor-associated ones were effectively inhibited, with KIs in the range of 22.1-481nM for CA IX and of 3.9-245nM for hCA XII. Although the inhibition mechanism of these tertiary/secondary sulfonamides is unknown for the moment, the good efficacy and especially selectivity for the inhibition of the tumor-associated over the cytosolic, widespread isoforms, make these derivatives of considerable interest as enzyme inhibitors with various pharmacologic applications.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2017-03-15 | Bioorganicmedicinal chemistry |