Pyrazolo[4,3-e][1,2,4]triazine sulfonamides as carbonic anhydrase inhibitors with antitumor activity

Bioorg Med Chem. 2014 May 1;22(9):2643-7. doi: 10.1016/j.bmc.2014.03.029. Epub 2014 Mar 27.

Abstract

A series of sildenafil analogues and aniline substituted pyrazolo[4,3-e][1,2,4]triazine sulfonamides were prepared and evaluated as carbonic anhydrase (CA, EC 4.2.1.1) inhibitors and for their anticancer activity against two human breast cancer cell lines (MCF-7, MDA-MB-231). The new compounds were ineffective as CA I inhibitors, poorly inhibited CA II, but were more effective against the tumor-associated isoforms CA IX and XII, with some compounds acting as low nanomolar inhibitors. Evaluation of the cytotoxicity by using an MTT assay, the inhibition of [(3)H]thymidine incorporation into DNA as well as collagen synthesis inhibition, demonstrated that these sulfonamides exhibit cytotoxic effects on breast cancer cell lines ex vivo.

Keywords: Carbonic anhydrase inhibitors; Cytotoxicity; MCF-7; MDA-MB-231; Pyrazolo[4,3-e][1,2,4]triazine; Sulfonamides.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / toxicity
  • Carbonic Anhydrase Inhibitors / chemical synthesis
  • Carbonic Anhydrase Inhibitors / chemistry*
  • Carbonic Anhydrase Inhibitors / toxicity
  • Carbonic Anhydrases / chemistry*
  • Carbonic Anhydrases / metabolism
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Humans
  • MCF-7 Cells
  • Pyrazoles / chemistry*
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry*
  • Sulfonamides / toxicity
  • Triazines / chemistry*

Substances

  • Antineoplastic Agents
  • Carbonic Anhydrase Inhibitors
  • Pyrazoles
  • Sulfonamides
  • Triazines
  • pyrazole
  • Carbonic Anhydrases