Carbonic Anhydrase Inhibitors. Biphenylsulfonamides With Inhibitory Action Towards the Transmembrane, Tumor-Associated Isozymes IX Possess Cytotoxic Activity Against Human Colon, Lung and Breast Cancer Cell Lines

J Enzyme Inhib Med Chem. 2009 Apr;24(2):499-505. doi: 10.1080/14756360802218441.

Abstract

Reaction of 4,4-biphenyl-disulfonyl chloride with aromatic/heterocyclic sulfonamides also incorporating a free amino group, such as 4-aminobenzenesulfonamide, 4-aminoethyl-benzenesulfonamide, 6-chloro-4-aminobenzene-1,3-disulfonamide or 5-amino-1,3,4-thiadiazole-2-sulfonamide afforded bis-sulfonamides which have been tested as inhibitors of the zinc enzyme carbonic anhydrase (CA, EC 4..2.1.1). The compounds were rather modest inhibitors of isozymes CA I and XII, but were more efficient as inhibitors of the cytosolic CA II and transmembrane, tumor-associated CA IX (inhibition constants in the range of 21-129 nM gainst hCA II, and 23-79 nM against hCA IX, respectively). The new bis-sulfonamides also showed inhibition of growth of several tumor cell lines (ex vivo), with GI(50) values in the range of 0.74-10.0 microg/mL against the human colon cancer cell line HCT116, the human lung cancer cell line H460 and the human breast cancer cell line MCF-7.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / toxicity*
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / metabolism
  • Carbonic Anhydrase Inhibitors / toxicity*
  • Carbonic Anhydrases / metabolism*
  • Colonic Neoplasms / enzymology
  • Colonic Neoplasms / metabolism
  • Dose-Response Relationship, Drug
  • Female
  • HCT116 Cells
  • Humans
  • Isoenzymes / antagonists & inhibitors
  • Isoenzymes / metabolism
  • Lung Neoplasms / enzymology
  • Lung Neoplasms / metabolism
  • Sulfonamides / toxicity*

Substances

  • Antineoplastic Agents
  • Carbonic Anhydrase Inhibitors
  • Isoenzymes
  • Sulfonamides
  • Carbonic Anhydrases