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. (October 2015)

• Record Type: Journal Article
• Authors: Vullo, Daniela; Isik, Semra; Bozdag, Murat; Carta, Fabrizio; Supuran, Claudiu T.
• Is Part Of: Journal of enzyme inhibition and medicinal chemistry. Volume 30:Number 5(2015:Oct.)
• Page Start: 773
• Page End: 777
• Publication Date: 2015-10
• Subjects: Enzyme inhibitors -- Periodicals; Enzyme Inhibitors -- periodicals; Biochemistry -- periodicals; 572.7
• Languages: English
• ISSNs: 1475-6366

Abstract

<abstract> <title>Abstract</title> <p>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 &gt; 10 µM), was a weak inhibitor of hCA I, III, IV, VA, VI and XIII (K_Is 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_Is 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.</p> </abstract>