Pyridazinone substituted benzenesulfonamides as potent carbonic anhydrase inhibitors

Yaseen R., EKİNCİ D., ŞENTÜRK M., Hameed A. D., Ovais S., Rathore P., ...More

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, vol.26, no.4, pp.1337-1341, 2016 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 26 Issue: 4
  • Publication Date: 2016
  • Doi Number: 10.1016/j.bmcl.2015.12.016
  • Journal Name: BIOORGANIC & MEDICINAL CHEMISTRY LETTERS
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus, Index Chemicus (IC)
  • Page Numbers: pp.1337-1341
  • Keywords: Human carbonic anhydrase, Enzyme inhibitors, Sulfonamides, IN-VITRO INHIBITION, ISOZYME-II, ISOFORMS I, DERIVATIVES, SULFONAMIDE, PURIFICATION, ANTITUMOR, BINDING, DRUGS, VI
  • Ondokuz Mayıs University Affiliated: Yes

Abstract

A series of sulfonamide derivatives (2a-l) incorporating substituted pyridazinone moieties were investigated for the inhibition of two human cytosolic carbonic anhydrase isoforms, hCA I and hCA II. All these compounds, together with the clinically used sulfonamide acetazolamide were investigated as inhibitors of the physiologically relevant isozymes I and II. These sulfonamides showed very strong inhibition against all these isoforms with K-I's in the range of 0.98-8.5 nM which makes such molecules possible to be used as leads for discovery of novel effective CA inhibitors targeting other isoforms with medicinal chemistry applications. (C) 2016 Elsevier Ltd. All rights reserved.