Kinetic and in silico analysis of thiazolidin-based inhibitors of alpha-carbonic anhydrase isoenzymes

EKİNCİ D., FİDAN İ., DURDAĞI S., KABAN Ş., Supuran C. T.

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, vol.28, no.2, pp.370-374, 2013 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 28 Issue: 2
  • Publication Date: 2013
  • Doi Number: 10.3109/14756366.2012.732071
  • Journal Name: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.370-374
  • Keywords: Carbonic anhydrase, thiazolidin, sulfonamide, docking, enzyme inhibition, THERAPEUTIC APPLICATIONS, ISOZYMES I, PURIFICATION, DERIVATIVES
  • Ondokuz Mayıs University Affiliated: Yes

Abstract

Carbonic anhydrases (CAs, EC 4.2.1.1) are inhibited by sulfonamides, inorganic anions, phenols, salicylic acid derivatives (acting as drug or prodrugs). A novel class of CA inhibitors (CAIs), interacting with the CA isozymes I and II (cytosolic) in a different manner, is reported here. Kinetic measurements allowed us to identify thiazolidin-based compounds as submicromolar-low micromolar inhibitors of these two CA isozymes. Molecular docking studies of a set of such inhibitors within CA I and II active site allowed us to understand the inhibition mechanism. This new class of inhibitors bind differently compared to other classes of inhibitors known to date: they were found between the phenol-binding site, filling thus the middle of the enzyme cavity.