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

Innocenti, Alessio; SARIKAYA, S. Beyza Oeztuerk; Gülçin, İlhami; SUPURAN, Claudiu T.

doi:10.1016/j.bmc.2010.01.076

Makale Tam Makale Uluslararası 2010

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

Alessio Innocenti, S. Beyza Oeztuerk SARIKAYA, İlhami Gülçin, Claudiu T. SUPURAN

BIOORGANIC & MEDICINAL CHEMISTRY Cilt 18 · Sayı 6 · ss. 2159–2164 · 15.03.2010

DOI ile aç

Özet

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 mu M). p-Hydroxybenzoic acid was the best inhibitor of all isozymes (K(I)s of 0.87-35.4 mu M) 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. (C) 2010 Elsevier Ltd. All rights reserved.

Anahtar kelimeler

CANCER hypoxia carbonic anhydrase COUMARINS Natural products THERAPEUTIC APPLICATIONS phenols SULFONAMIDES ACTIVATORS ANTITUMOR X-RAY PHENOLIC-ACIDS ACTIVE-SITE Isozymes I-XIV Enzyme inhibition mechanism ISOZYME-II

Atıf için künye

Innocenti, A., SARIKAYA, S. B. O., Gülçin, İ., & SUPURAN, C. T. (2010). Carbonic anhydrase inhibitors. Inhibition of mammalian isoforms I-XIV with a series of natural product polyphenols and phenolic acids. BIOORGANIC & MEDICINAL CHEMISTRY, 18(6), 2159–2164. https://doi.org/10.1016/j.bmc.2010.01.076

BibTeX

@article{innocenti2010-67934,
  author = {Innocenti, Alessio and SARIKAYA, S. Beyza Oeztuerk and Gülçin, İlhami and SUPURAN, Claudiu T.},
  title = {Carbonic anhydrase inhibitors. Inhibition of mammalian isoforms I-XIV with a series of natural product polyphenols and phenolic acids},
  journal = {BIOORGANIC & MEDICINAL CHEMISTRY},
  year = {2010},
  volume = {18},
  number = {6},
  pages = {2159--2164},
  issn = {0968-0896},
  doi = {10.1016/j.bmc.2010.01.076},
  url = {https://akademik.atauni.edu.tr/yayinlar/67934-carbonic-anhydrase-inhibitors-inhibition-of-mammalian-isoforms-i-xiv-with-a}
}