Carbonic anhydrase inhibitors. The nematode alpha-carbonic anhydrase of Caenorhabditis elegans CAH-4b is highly inhibited by 2-(hydrazinocarbonyl)-3-substituted-phenyl-1H-indole-5-sulfonamides

Guzel O., Innocenti A., Hall R. A., Scozzafava A., Muhlschlegel F. A., Supuran C. T.

BIOORGANIC & MEDICINAL CHEMISTRY, vol.17, no.8, pp.3212-3215, 2009 (SCI-Expanded) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 17 Issue: 8
  • Publication Date: 2009
  • Doi Number: 10.1016/j.bmc.2009.01.048
  • Journal Name: BIOORGANIC & MEDICINAL CHEMISTRY
  • Journal Indexes: Science Citation Index Expanded (SCI-EXPANDED), Scopus
  • Page Numbers: pp.3212-3215
  • Istanbul University Affiliated: Yes

Abstract

A series of 2-(hydrazinocarbonyl)-3-substituted-phenyl-1H-indole-5-sulfonamides possessing various 2-, 3- or 4-substituted phenyl groups with methyl-, halogeno- and methoxy-functionalities, as well as the perfluorophenyl moiety, have been evaluated as inhibitors of an alpha-carbonic anhydrase (CA, EC 4.2.1.1) of the nematode model organism Caenorhabditis elegans (CAH-4b, or ceCA). The substitution pattern at the 3- phenyl ring highly influenced the ceCA inhibitory activity of these heterocyclic sulfonamides, with best inhibitors (K(I)s in the range of 6.0 - 13.4 nM) incorporating 3- methyl-, 4- methyl-, 2-/3-/4-fluoro-, 4chloro- and 3-/4-bromo-phenyl such moieties. Some of these sulfonamides also showed a good selectivity pro. le for the inhibition of the nematode over the human isozymes CA I and II ( selectivity ratios in the range of 1.78 - 4.95 for the inhibition of ceCA over hCA II). These data can be used for the design of possibly new antihelmintic drugs, since the genome of many parasitic nematodes encode for a multitude of orthologue CA isozymes to ceCA investigated here. (C) 2009 Elsevier Ltd. All rights reserved.