Discovery of Strecker-type α-aminonitriles as a new class of human carbonic anhydrase inhibitors using differential scanning fluorimetry

J Enzyme Inhib Med Chem. 2016 Dec;31(6):1707-11. doi: 10.3109/14756366.2016.1156676. Epub 2016 Mar 16.

Abstract

A new type of carbonic anhydrase inhibitors was identified via differential scanning fluorimetry (DSF) screening. The compounds displayed interesting inhibition profile against human carbonic anhydrase isoforms I, II, IX and XII with an obvious selectivity displayed by one compound toward carbonic anhydrase (CA) IX, an established anti-cancer target. A hypothetical mechanism of inhibitory action by the Strecker-type α-aminonitriles has been proposed.

Keywords: Carbonic anhydrases; cyanide donors; differential scanning fluorimetry; isoform selectivity; protein affinity; suicide inhibitors; thermal shift assay.

MeSH terms

  • Carbonic Anhydrase Inhibitors / chemistry*
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Fluorometry / methods*
  • Nitriles / chemistry*
  • Nitriles / pharmacology*

Substances

  • Carbonic Anhydrase Inhibitors
  • Nitriles