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

Ozlen Güzel, Alessio Innocenti, Rebecca Hall, Andrea Scozzafava, Fritz A Mühlschlegel, Claudiu T Supuran

Research output: Contribution to journalArticlepeer-review

15 Citations (Scopus)

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-, 4-chloro- and 3-/4-bromo-phenyl such moieties. Some of these sulfonamides also showed a good selectivity profile 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.
Original languageEnglish
Pages (from-to)3212-5
Number of pages4
JournalBioorganic & Medicinal Chemistry
Volume17
Issue number8
DOIs
Publication statusPublished - 15 Apr 2009

Keywords

  • Animals
  • Caenorhabditis elegans
  • Carbonic Anhydrase Inhibitors
  • Carbonic Anhydrases
  • Humans
  • Hydrazines
  • Indoles
  • Isoenzymes
  • Molecular Structure
  • Structure-Activity Relationship
  • Sulfonamides

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