Synthesis of novel acridine bis-sulfonamides with effective inhibitory activity against the carbonic anhydrase isoforms I, II, IX and XII

Bioorg Med Chem. 2015 Oct 15;23(20):6573-80. doi: 10.1016/j.bmc.2015.09.022. Epub 2015 Sep 15.

Abstract

By using a multi component reaction system (MCR), nitro acridine sulfonamides were obtained from cyclic-1,3-diketones, 4-aminobenzene sulfonamide and aromatic aldehydes. Some novel acridine bis-sulfonamides 6a-l were then synthesized by the reaction between sulfonyl chlorides and the novel amino-acridine sulfonamides 5a and 5b, obtained by reduction of nitro-acridine sulfonamide derivatives 4a and 4b. The newly synthesized compounds were investigated as inhibitors of 4 human carbonic anhydrase isoforms (hCA, EC 4.2.1.1). Several of the compounds showed low micromolar inhibition against the medically relevant isoforms hCA I, II, IX, and XII.

Keywords: Acridine; Carbonic anhydrase; Enzyme inhibition; Isoforms CA I, II, IX and VII; Sulfonamide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / metabolism*
  • Carbonic Anhydrase I / antagonists & inhibitors*
  • Carbonic Anhydrase I / metabolism
  • Carbonic Anhydrase II / antagonists & inhibitors*
  • Carbonic Anhydrase II / metabolism
  • Carbonic Anhydrase IX
  • Carbonic Anhydrase Inhibitors / chemical synthesis
  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Carbonic Anhydrases / metabolism*
  • Dose-Response Relationship, Drug
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Antigens, Neoplasm
  • Carbonic Anhydrase Inhibitors
  • Carbonic Anhydrase I
  • Carbonic Anhydrase II
  • CA9 protein, human
  • Carbonic Anhydrase IX
  • Carbonic Anhydrases
  • carbonic anhydrase XII