New Isoindole-1,3-dione Substituted Sulfonamides as Potent Inhibitors of Carbonic Anhydrase and Acetylcholinesterase: Design, Synthesis, and Biological Evaluation


Gundogdu S., Türkeş C., Arslan M., Demir Y., Beydemir S.

CHEMISTRYSELECT, vol.4, no.45, pp.13347-13355, 2019 (SCI-Expanded) identifier identifier

  • Publication Type: Article / Article
  • Volume: 4 Issue: 45
  • Publication Date: 2019
  • Doi Number: 10.1002/slct.201903458
  • Journal Name: CHEMISTRYSELECT
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.13347-13355
  • Keywords: Acetylcholinesterase, Carbonic Anhydrase, Isoindole, Molecular Docking, Sulfonamide, DERIVATIVES, SOLUBILITY, PREDICTION, BINDING, DRUGS
  • Erzincan Binali Yildirim University Affiliated: Yes

Abstract

Herein, a series of isoindole-1,3-dione substituted sulfonamide derivatives (3, 4a-k) were designed, synthesized, and biologically evaluated, as inhibitors of carbonic anhydrase (CA) and acetylcholinesterase (AChE). CA and AChE inhibitory activities of newly synthesized isoindole-1,3-dione substituted sulfonamides compounds (3, 4a-k) towards the hCA I, II, and AChE were evaluated utilizing the Verpoorte's and Ellman's assays and checked against that of standard inhibitors, acetazolamide (AAZ) and tacrine (TAC). The developed compounds (3, 4a-k) showed the potent hCA isoenzyme inhibitory effect with K-i constants ranging from 7.96 to 48.34 nM, compared to AAZ (K(i)s; 436.20 nM for hCA I and 93.53 nM for hCA II). Among these derivatives; 1,3-dioxo-1,3-dihydroisobenzofuran-5-carbocyclic acid (3) and benzyl-1,3-dioxo-2-(4-sulfomophenyl)isoindoline-5-carboxylate (4i) determined to be effective AChE inhibitors (K(i)s, 103.51 and 108.92 nM, respectively); these compounds were almost as potent to TAC (K-i, 109.75 nM). Furthermore, molecular docking studies of derivatives 3 and 4i were carried out utilizing the crystal structures of hCA I (PDB Code: 4WR7), II (PDB Code: 4HT0) isozymes and AChE (PDB Code: 4EY7) receptors to study their binding interactions.