Synthesis of 3,4-dihydroxypyrrolidine-2,5-dione and 3,5-dihydroxybenzoic acid derivatives and evaluation of the carbonic anhydrase I and II inhibition

ARSLAN M., ŞENTÜRK M., Fidan I., TALAZ O., EKİNCİ D., Cosgun S., ...More

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, vol.30, no.6, pp.896-900, 2015 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 30 Issue: 6
  • Publication Date: 2015
  • Doi Number: 10.3109/14756366.2014.983917
  • Journal Name: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.896-900
  • Keywords: Benzoic acid, carbonic anhydrase, enzyme inhibitor, hydroxyl, pyrrolidine, SOLID-PHASE SYNTHESIS, MYCOBACTERIUM-TUBERCULOSIS, MULTICOMPONENT REACTION, SULFONAMIDE INHIBITORS, PHENOLIC-COMPOUNDS, ISOZYMES I, ISOFORMS I, BENZENESULFONAMIDES, ALKYLATION, ACTIVATORS
  • Ondokuz Mayıs University Affiliated: Yes

Abstract

The inhibition of two human cytosolic carbonic anhydrase (hCA, EC 4.2.1.1) isozymes I and II, with some 3,4-dihydroxypyrrolidine-2,5-dione and 3,5-dihydroxybenzoic acid derivatives, were investigated by using the esterase assay, with 4-nitrophenyl acetate (4-NPA) as substrate. Compounds 10-13 showed K-I values in the range of 112.7-441.5 mu M for hCA I and of 3.5-10.76 mu M against hCA II, respectively. These hydroxyl group containing compounds generally were competitive inhibitors. Some hydroxyl group containing compounds investigated here showed effective hCA II inhibitory effects, in the same range as the clinically used sulfonamide acetazolamide, and might be used as leads for generating enzyme inhibitors possibly targeting other CA isoforms which have not been yet assayed for their interactions with such agents.