Isatin analogs as novel inhibitors of Candida spp. β-carbonic anhydrase enzymes

Bioorg Med Chem. 2016 Apr 15;24(8):1648-52. doi: 10.1016/j.bmc.2016.02.036. Epub 2016 Feb 27.

Abstract

Enzyme inhibition data of structurally novel isatin-containing sulfonamides were determined for two carbonic anhydrases (CAs, EC 4.2.1.1) from pathogenic Candida species (CaNce103 from C. albicans and CgNce103 from C. glabrata). The compounds show KI values in the low nanomolar range for the fungal CAs, while they have significantly higher KI values for the human CAs. Homology models were constructed for the CaNce103 and CgNce103 and subsequently the ligands were docked into these models to rationalize their enzyme inhibitory properties.

Keywords: Candida; Carbonic anhydrase; Carbonic anhydrase inhibitors; Isatins; Sulfonamides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Candida / enzymology*
  • Carbonic Anhydrases / metabolism*
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Isatin / analogs & derivatives*
  • Isatin / chemical synthesis
  • Isatin / chemistry
  • Isatin / pharmacology*
  • Ligands
  • Models, Molecular
  • Molecular Structure
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*

Substances

  • Enzyme Inhibitors
  • Ligands
  • Sulfonamides
  • Isatin
  • Carbonic Anhydrases