Carbonic Anhydrase Inhibitors. Inhibition of the Fungal Beta-Carbonic Anhydrases From Candida Albicans and Cryptococcus Neoformans With Boronic Acids

Bioorg Med Chem Lett. 2009 May 15;19(10):2642-5. doi: 10.1016/j.bmcl.2009.03.147. Epub 2009 Apr 5.

Abstract

Inhibition of the beta-carbonic anhydrases (CAs, EC 4.2.1.1) from the pathogenic fungi Cryptococcus neoformans (Can2) and Candida albicans (Nce103) with a series of aromatic, arylalkenyl- and arylalkylboronic acids was investigated. Aromatic, 4-phenylsubstituted- and 2-naphthylboronic acids were the best Can2 inhibitors, with inhibition constants in the range of 8.5-11.5microM, whereas arylalkenyl and aryalkylboronic acids showed K(I)s in the range of 428-3040microM. Nce103 showed a similar inhibition profile, with the 4-phenylsubstituted- and 2-naphthylboronic acids possessing K(I)s in the range of 7.8-42.3microM, whereas the arylalkenyl and aryalkylboronic acids were weaker inhibitors (K(I)s of 412-5210microM). The host human enzymes CA I and II were also effectively inhibited by these boronic acids. The B(OH)(2) moiety is thus a new zinc-binding group for designing effective inhibitors of the alpha- and beta-CAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Boronic Acids / chemical synthesis
  • Boronic Acids / chemistry*
  • Boronic Acids / pharmacology
  • Candida albicans / enzymology*
  • Carbonic Anhydrase Inhibitors / chemical synthesis
  • Carbonic Anhydrase Inhibitors / chemistry*
  • Carbonic Anhydrase Inhibitors / pharmacology
  • Carbonic Anhydrases / chemistry*
  • Carbonic Anhydrases / metabolism
  • Cryptococcus neoformans / enzymology*
  • Humans
  • Structure-Activity Relationship

Substances

  • Boronic Acids
  • Carbonic Anhydrase Inhibitors
  • Carbonic Anhydrases