Fluorescent Silica Nanoparticles with Multivalent Inhibitory Effects towards Carbonic Anhydrases

Chemistry. 2015 Jul 13;21(29):10306-9. doi: 10.1002/chem.201501037. Epub 2015 May 12.

Abstract

Multifunctional silica nanoparticles decorated with fluorescent and sulfonamide carbonic anhydrase (CA) inhibitors were prepared and investigated as multivalent enzyme inhibitors against the cytosolic isoforms hCA I and II and the transmembrane tumor-associated ones hCA IX and XII. Excellent inhibitory effects were observed with these nanoparticles, with KI values in the low nanomolar range (6.2-0.67 nM) against all tested isozymes. A significant multivalency effect was seen for the inhibition of the monomeric enzymes hCA I and II compared to the dimeric hCA IX and hCA XII isoforms, where no multivalent effect was observed, suggesting that the multivalent binding is occurring through enzyme clustering.

Keywords: carbonic anhydrase; inhibitors; multivalency; nanoparticles; sulfonamide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / chemistry*
  • Antigens, Neoplasm / metabolism
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology
  • Carbonic Anhydrase I / antagonists & inhibitors*
  • Carbonic Anhydrase I / chemistry
  • Carbonic Anhydrase I / metabolism
  • Carbonic Anhydrase II / antagonists & inhibitors*
  • Carbonic Anhydrase II / chemistry
  • Carbonic Anhydrase II / metabolism
  • Carbonic Anhydrase Inhibitors / chemistry*
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Carbonic Anhydrases / metabolism
  • Cell Line, Tumor
  • Cytosol / chemistry
  • Cytosol / drug effects*
  • Cytosol / enzymology
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Humans
  • Isoenzymes / antagonists & inhibitors*
  • Isoenzymes / chemistry
  • Isoenzymes / metabolism*
  • Molecular Structure
  • Nanoparticles / chemistry*
  • Neoplasms / chemistry*
  • Neoplasms / drug therapy*
  • Neoplasms / enzymology
  • Silicon Dioxide / chemistry*
  • Structure-Activity Relationship

Substances

  • Antigens, Neoplasm
  • Antineoplastic Agents
  • Carbonic Anhydrase Inhibitors
  • Enzyme Inhibitors
  • Isoenzymes
  • Silicon Dioxide
  • Carbonic Anhydrase I
  • Carbonic Anhydrase II
  • Carbonic Anhydrases