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., ...Daha Fazla

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, cilt.30, sa.6, ss.896-900, 2015 (SCI-Expanded) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 30 Sayı: 6
  • Basım Tarihi: 2015
  • Doi Numarası: 10.3109/14756366.2014.983917
  • Dergi Adı: JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Sayfa Sayıları: ss.896-900
  • Anahtar Kelimeler: 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 Üniversitesi Adresli: Evet

Özet

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.