Carbonic anhydrase inhibitors. Antioxidant polyphenols effectively inhibit mammalian isoforms I-XV.
A series of polyphenolic derivatives, including resveratrol, dobutamine, curcumin, catechin and silymarine were investigated for the inhibition of all the catalytically active mammalian isozymes of the metalloprotein carbonic anhydrase (CA, EC 4.2.1.1), that is, CA I-CA XV. These polyphenols effectively inhibited CAs, with K(I)s in the range of 380 nM-12.02 microM. The various isozymes showed quite diverse inhibition profiles with these compounds, which possess scaffolds not present in other investigated CA inhibitors (CAIs). These data may lead to drug design campaigns of effective CAIs possessing a diverse inhibition mechanism compared to sulfonamide/sulfamate inhibitors, based on such less investigated scaffolds.
Innocenti
Alessio
A
Università degli Studi di Firenze, Laboratorio di Chimica Bioinorganica, Sesto Fiorentino (Firenze), Italy.
Gülçin
Ilhami
I
Scozzafava
Andrea
A
Supuran
Claudiu T
CT
D000975:Antioxidants / Q000494:pharmacology*; D002257:Carbonic Anhydrase Inhibitors / Q000494:pharmacology*; D015195:Drug Design; D005419:Flavonoids / Q000494:pharmacology*; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D010636:Phenols / Q000494:pharmacology*; D059808:Polyphenols
D000975:Antioxidants; D002257:Carbonic Anhydrase Inhibitors; D005419:Flavonoids; D007527:Isoenzymes; D010636:Phenols; D059808:Polyphenols