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  • Carbonic anhydrase inhibitors. Inhibition of mammalian isoforms I-XIV with a series of natural product polyphenols and phenolic acids.

Carbonic anhydrase inhibitors. Inhibition of mammalian isoforms I-XIV with a series of natural product polyphenols and phenolic acids.

Bioorganic & medicinal chemistry (2010-02-27)
Alessio Innocenti, S Beyza Oztürk Sarikaya, Ilhami Gülçin, Claudiu T Supuran
ZUSAMMENFASSUNG

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.

MATERIALIEN
Produktnummer
Marke
Produktbeschreibung

Sigma-Aldrich
Phenol -Lösung, Equilibrated with 10 mM Tris HCl, pH 8.0, 1 mM EDTA, BioReagent, for molecular biology
Sigma-Aldrich
Gallussäure, 97.5-102.5% (titration)
Sigma-Aldrich
Kaffeesäure, ≥98.0% (HPLC)
Sigma-Aldrich
p-Coumarsäure, ≥98.0% (HPLC)
Sigma-Aldrich
4-Hydroxybenzoesäure, ReagentPlus®, ≥99%
Sigma-Aldrich
4-Hydroxybenzoesäure, ReagentPlus®, 99%
Sigma-Aldrich
trans-Ferulasäure, 99%
Sigma-Aldrich
Phenol, ≥99%
Sigma-Aldrich
Phenol -Lösung, BioReagent, Saturated with 0.01 M citrate buffer, pH 4.3 ± 0.2, for molecular biology
Sigma-Aldrich
Ellagsäure, ≥95% (HPLC), powder, from tree bark
Sigma-Aldrich
Syringasäure, ≥95% (HPLC)
Supelco
Phenol -Lösung, certified reference material, 500 μg/mL in methanol
Sigma-Aldrich
Phenol, BioUltra, for molecular biology, TE-saturated, ~73% (T)
Sigma-Aldrich
trans-Ferulasäure, ≥99%
Supelco
Phenol -Lösung, 5000 μg/mL in methanol, certified reference material
Sigma-Aldrich
Phenol, puriss. p.a., ACS reagent, reag. Ph. Eur., 99.0-100.5%
Sigma-Aldrich
Verflüssigtes Phenol, ≥89.0%
Sigma-Aldrich
Phenol, for molecular biology
Sigma-Aldrich
1,2-Dihydroxybenzol, ReagentPlus®, ≥99%
Sigma-Aldrich
Brenzcatechin, ≥99%
Sigma-Aldrich
Gallussäure Monohydrat, ACS reagent, ≥98.0%
Sigma-Aldrich
Gallussäure Monohydrat, ≥99% (HPLC)
Sigma-Aldrich
Phenol, puriss., ≥99.5% (GC), meets analytical specification of Ph. Eur., BP, USP, crystalline (detached)
Sigma-Aldrich
Phenol, BioXtra, ≥99.5% (GC)
Sigma-Aldrich
Phenol, ACS reagent, ≥99.0%
Sigma-Aldrich
Phenol, unstabilized, ReagentPlus®, ≥99%
Supelco
trans-Ferulasäure, matrix substance for MALDI-MS, ≥99.0% (HPLC)
Supelco
Phenol, PESTANAL®, analytical standard
Sigma-Aldrich
Phenol, unstabilized, purified by redistillation, ≥99%
Supelco
Phenol -Lösung, 100 μg/mL in acetonitrile, PESTANAL®, analytical standard