title: 7-Amino-3,4-dihydro-1H-quinolin-2-one, a compound similar to the substituted coumarins, inhibits α-carbonic anhydrases without hydrolysis of the lactam ring.
abstract: 7-Amino-3,4-dihydro-1H-quinolin-2-one, a compound structurally similar to coumarins, recently discovered class of inhibitors of the α-carbonic anhydrases (CAs, EC 4.2.1.1) was investigated for its interaction with all human (h) CA isoforms, hCA I-XIV. The compound was not an inhibitor of the cytosolic, widespread isoform hCA II (K(I) > 10 µM), was a weak inhibitor of hCA I, III, IV, VA, VI and XIII (K(I)s in the range of 0.90-9.5 µM) but effectively inhibited the cytosolic isoform hCA VII (K(I) of 480 nM) as well as the transmembrane isoforms hCA IX, XII and XIV (K(I)s in the range of 16.1-510 nM). Against many CA isoforms this lactam was a better inhibitor compared to the structurally similar 4-methyl-7-aminocoumarin, but unlike this compound, the lactam ring was not hydrolyzed and the inhibition was due to the intact bicyclic amino-quinolinone scaffold. Bicyclic lactams strucurally related to coumarins are thus a new class of CA inhibitors possessing however a distinct inhibition mechanism compared to the coumarins which undergo a hydrolysis of their lactone ring for generating the enzyme inhibitory species.
authors: a Department of Chemistry "Ugo Shiff" , University of Florence , Sesto Fiorentino , Italy .
authors: Daniela
authors: D
authors: Vullo
authors: Semra
authors: S
authors: Isik
authors: Murat
authors: M
authors: Bozdag
authors: Fabrizio
authors: F
authors: Carta
authors: Claudiu T
authors: CT
authors: Supuran
mesh_terms: D000634:Aminoquinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002257:Carbonic Anhydrase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002256:Carbonic Anhydrases / Q000378:metabolism*; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D006868:Hydrolysis; D007527:Isoenzymes / Q000037:antagonists & inhibitors / Q000378:metabolism; D007769:Lactams / Q000737:chemistry*; D015394:Molecular Structure; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C000607913:7-amino-3,4-dihydro-1H-quinolin-2-one; D000634:Aminoquinolines; D002257:Carbonic Anhydrase Inhibitors; D003374:Coumarins; D007527:Isoenzymes; D007769:Lactams; D015363:Quinolones; D002256:Carbonic Anhydrases
keywords: Carbonic anhydrase; coumarin; inhibitor; isoform-selectivity; lactam; lactone; quinolon-2-one