Synthesis of 4-(thiazol-2-ylamino)-benzenesulfonamides with carbonic anhydrase I, II and IX inhibitory activity and cytotoxic effects against breast cancer cell lines

Bioorg Med Chem. 2016 Jul 1;24(13):3043-3051. doi: 10.1016/j.bmc.2016.05.016. Epub 2016 May 12.

Abstract

A series of 4-(thiazol-2-ylamino)-benzenesulfonamides was synthesized and screened for their carbonic anhydrase (CA, EC 4.2.1.1) inhibitory and cytotoxic activity on human breast cancer cell line MCF-7. Human (h) CA isoforms I, II and IX were included in the study. The new sulfonamides showed excellent inhibition of all three isoforms, with KIs in the range of 0.84-702nM against hCA I, of 0.41-288nM against hCA II and of 5.6-29.2 against the tumor-associated hCA IX, a validated anti-tumor target, with a sulfonamide (SLC-0111) in Phase I clinical trials for the treatment of hypoxic, metastatic solid tumors overexpressing CA IX. The new compounds showed micromolar inhibition of growth efficacy against breast cancer MCF-7 cell lines.

Keywords: Antitumor; Carbonic anhydrase; Cytotoxic agent; Inhibitor; Sulfonamide.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Benzenesulfonamides
  • Breast Neoplasms / drug therapy
  • Carbonic Anhydrase Inhibitors / chemical synthesis*
  • Carbonic Anhydrase Inhibitors / chemistry
  • Carbonic Anhydrase Inhibitors / pharmacology*
  • Carbonic Anhydrase Inhibitors / toxicity
  • Carbonic Anhydrases / metabolism
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Drug Delivery Systems
  • Female
  • Humans
  • Inhibitory Concentration 50
  • MCF-7 Cells
  • Molecular Structure
  • Sulfonamides / chemical synthesis*
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*
  • Thiazoles / chemistry

Substances

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