New sulfonamides containing organometallic-acylhydrazones: synthesis, characterisation and biological evaluation as inhibitors of human carbonic anhydrases

J Enzyme Inhib Med Chem. 2019 Dec;34(1):451-458. doi: 10.1080/14756366.2018.1555156.

Abstract

A series of organometallic acylhydrazones was prepared, incorporating Re(CO)3, Mn(CO)3 and ferrocenyl moieties, which were subsequently reacted with amino-sulfonamides in order to obtain carbonic anhydrase (CA, EC 4.2.1.1) inhibitors possessing organometallic moieties in their molecules. The new derivatives were investigated as inhibitors of four human (h) CA isoforms with pharmaceutical applications, such as the cytosolic hCA I, II and VII and the mitochondrial hCA VA. An interesting inhibitory profile against these isoforms was obtained, with some of these metal complexes acting as subnanomolar or low nanomolar inhibitors. They were also thoroughly characterised from the chemical point of view, making them of interest for further developments in the field of metal complexes of sulfonamides with CA inhibitory action.

Keywords: Organometallic-acylhydrazones; carbonic anhydrase; inhibitors; sulfonamides.

MeSH terms

  • Carbonic Anhydrase Inhibitors / chemical synthesis
  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Carbonic Anhydrases / metabolism*
  • Dose-Response Relationship, Drug
  • Humans
  • Hydrazones / chemistry
  • Hydrazones / pharmacology*
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Molecular Structure
  • Organometallic Compounds / chemistry
  • Organometallic Compounds / pharmacology*
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*

Substances

  • Carbonic Anhydrase Inhibitors
  • Hydrazones
  • Isoenzymes
  • Organometallic Compounds
  • Sulfonamides
  • Carbonic Anhydrases

Grants and funding

R.A and N.N acknowledge FONDECYT-Chile [Project 11130443, 1110669]. R.A and Y.H. acknowledge VRID-UdeC [grant 216.021.034-1.0] for the funding of this study.