Molecules (Nov 2021)

Carbonic Anhydrase Inhibition with Sulfonamides Incorporating Pyrazole- and Pyridazinecarboxamide Moieties Provides Examples of Isoform-Selective Inhibitors

  • Andrea Angeli,
  • Victor Kartsev,
  • Anthi Petrou,
  • Mariana Pinteala,
  • Volodymyr Brovarets,
  • Roman Vydzhak,
  • Svitlana Panchishin,
  • Athina Geronikaki,
  • Claudiu T. Supuran

DOI
https://doi.org/10.3390/molecules26227023
Journal volume & issue
Vol. 26, no. 22
p. 7023

Abstract

Read online

A series of benzenesulfonamides incorporating pyrazole- and pyridazinecarboxamides decorated with several bulky moieties has been obtained by original procedures. The new derivatives were investigated for the inhibition of four physiologically crucial human carbonic anhydrase (hCA, EC 4.2.2.1.1) isoforms, hCA I and II (cytosolic enzymes) as well as hCA IX and XII (transmembrane, tumor-associated isoforms). Examples of isoform-selective inhibitors were obtained for all four enzymes investigated here, and a computational approach was employed for explaining the observed selectivity, which may be useful in drug design approaches for obtaining inhibitors with pharmacological applications useful as antiglaucoma, diuretic, antitumor or anti-cerebral ischemia drugs.

Keywords