Design, synthesis, biological evaluation and molecular modeling of dihydropyrazole sulfonamide derivatives as potential COX-1/COX-2 inhibitors

Bioorg Med Chem Lett. 2015 May 1;25(9):1947-51. doi: 10.1016/j.bmcl.2015.03.022. Epub 2015 Mar 22.

Abstract

Novel dihydropyrazole sulfonamide derivatives (30-56) were designed, synthesized, and evaluated for their biological activities as COX-1 and COX-2 inhibitors. In vitro biological evaluation against three human tumor cell lines revealed that most target compounds showed antiproliferative activities. Among the compounds, compound 48 exhibited the most potent and selective COX-2 inhibitor (COX-2 IC50=0.33 μM; COX-1 IC50=68.49 μM) relative to the reference drugs celecoxib (IC50=0.052 μM). Docking simulation was performed to position compound 48 into the COX-2 active site and the result showed that compound 48 could bind well at the COX-2 active site and it indicated that compound 48 could be a potent and selective COX-2 inhibitor.

Keywords: Anticancer; COX-1/COX-2; Dihydropyrazole sulfonamide; Docking; MTT.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclooxygenase 1 / metabolism*
  • Cyclooxygenase 2 / metabolism*
  • Cyclooxygenase Inhibitors / chemical synthesis
  • Cyclooxygenase Inhibitors / chemistry*
  • Cyclooxygenase Inhibitors / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Drug Screening Assays, Antitumor
  • HeLa Cells
  • Humans
  • MCF-7 Cells
  • Models, Molecular*
  • Molecular Structure
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry
  • Pyrazoles / pharmacology*
  • Structure-Activity Relationship
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry
  • Sulfonamides / pharmacology*

Substances

  • Antineoplastic Agents
  • Cyclooxygenase Inhibitors
  • Pyrazoles
  • Sulfonamides
  • Cyclooxygenase 1
  • Cyclooxygenase 2