Novel 2-indolinones containing a sulfonamide moiety as selective inhibitors of candida β-carbonic anhydrase enzyme

J Enzyme Inhib Med Chem. 2019 Dec;34(1):528-531. doi: 10.1080/14756366.2018.1564045.

Abstract

Inhibition of the β-carbonic anhydrase (CA, EC 4.2.1.1) from pathogenic Candida glabrata (CgNce103) by 1H-indole-2,3-dione 3-[N-(4-sulfamoylphenyl)thiosemicarbazones] 4a-m was investigated. All the compounds were found to be potent inhibitors of CgNce103, with inhibition constants in the range of 6.4-63.9 nM. The 5,7-dichloro substituted derivative 4l showed the most effective inhibition (KI of 6.4 nM) as well as the highest selectivity for inhibiting CgNce103 over the cytosolic human (h) isoforms hCA I and II. A possible binding interaction of compound 4l within the active site of CgNce103 has been proposed based on docking studies.

Keywords: Sulfonamides; carbonic anhydrase; docking.

MeSH terms

  • Candida albicans / enzymology*
  • Carbonic Anhydrase Inhibitors / chemical synthesis
  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Carbonic Anhydrases / metabolism*
  • Dose-Response Relationship, Drug
  • Molecular Docking Simulation
  • Molecular Structure
  • Oxindoles / chemical synthesis
  • Oxindoles / chemistry
  • Oxindoles / pharmacology*
  • Structure-Activity Relationship
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*

Substances

  • Carbonic Anhydrase Inhibitors
  • Oxindoles
  • Sulfonamides
  • 2-oxindole
  • Carbonic Anhydrases

Grants and funding

This work was supported by Istanbul University Scientific Research Projects, Project Number: ÖNAP-36808.