Carbonic anhydrase inhibitors. Inhibition of mammalian isoforms I-XIV with a series of natural product polyphenols and phenolic acids.
Article Details
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Innocenti A, Beyza Ozturk Sarikaya S, Gulcin I, Supuran CT
Carbonic anhydrase inhibitors. Inhibition of mammalian isoforms I-XIV with a series of natural product polyphenols and phenolic acids.
Bioorg Med Chem. 2010 Mar 15;18(6):2159-64. doi: 10.1016/j.bmc.2010.01.076. Epub 2010 Feb 6.
- PubMed ID
- 20185318 [ View in PubMed]
- Abstract
A series of phenolic acids and phenol natural products, such as p-hydroxybenzoic acid, p-coumaric acid, caffeic acid, ferulic acid, gallic acid, syringic acid, quercetin, and ellagic acid, were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). All mammalian isozymes of human (h) or murine (m) origin hCA I-hCA XII, mCA XIII and hCA XIV were inhibited in the low micromolar or submicromolar range by these (poly)phenols (K(I)s in the range of 0.87-7.79 microM). p-Hydroxybenzoic acid was the best inhibitor of all isozymes (K(I)s of 0.87-35.4 microM) and the different isozymes showed very variable inhibition profiles with these derivatives. Phenols like the ones investigated here possess a CA inhibition mechanism distinct of that of the sulfonamides/sulfamates used clinically or the coumarins. Unlike the sulfonamides, which bind to the catalytic zinc ion, phenols are anchored at the Zn(II)-coordinated water molecule and bind more externally within the active site cavity, making contacts with various amino acid residues. As this is the region with the highest variability between the many CA isozymes found in mammals, this class of compounds may lead to isoform-selective inhibitors targeting just one or few of the medicinally relevant CAs.
DrugBank Data that Cites this Article
- Drug Targets
Drug Target Kind Organism Pharmacological Action Actions Ellagic acid Carbonic anhydrase 1 Protein Humans UnknownInhibitorDetails Ellagic acid Carbonic anhydrase 12 Protein Humans UnknownInhibitorDetails Ellagic acid Carbonic anhydrase 14 Protein Humans UnknownInhibitorDetails Ellagic acid Carbonic anhydrase 2 Protein Humans UnknownInhibitorDetails Ellagic acid Carbonic anhydrase 3 Protein Humans UnknownInhibitorDetails Ellagic acid Carbonic anhydrase 4 Protein Humans UnknownInhibitorDetails Ellagic acid Carbonic anhydrase 5A, mitochondrial Protein Humans UnknownInhibitorDetails Ellagic acid Carbonic anhydrase 5B, mitochondrial Protein Humans UnknownInhibitorDetails Ellagic acid Carbonic anhydrase 6 Protein Humans UnknownInhibitorDetails Ellagic acid Carbonic anhydrase 7 Protein Humans UnknownInhibitorDetails Ellagic acid Carbonic anhydrase 9 Protein Humans UnknownInhibitorDetails - Binding Properties