Synthesis and mechanism of action of novel pyrimidinyl pyrazole derivatives possessing antiproliferative activity

Bioorg Med Chem Lett. 2002 Nov 4;12(21):3191-3. doi: 10.1016/s0960-894x(02)00568-1.

Abstract

Pyrimidinyl pyrazole derivatives 1-4, prepared as a new scaffold of an anti-tumor agent, showed antiproliferative activity against human lung cancer cell lines and inhibited tubulin polymerization. Furthermore, it was found that compound 2 bound at the colchicine site on tubulin, but the tubulin binding pattern was different from that of colchicine. Here, we describe the synthesis of the derivatives and the differences of the action mechanism on tubulin polymerization inhibition between compound 2 and colchicine.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology*
  • Binding, Competitive / drug effects
  • Colchicine / pharmacology
  • Drug Screening Assays, Antitumor
  • Humans
  • Indicators and Reagents
  • Lung Neoplasms / drug therapy
  • Lung Neoplasms / pathology
  • Microtubules / drug effects
  • Protein Binding / drug effects
  • Pyrazoles / chemical synthesis*
  • Pyrazoles / pharmacology*
  • Pyrimidines / chemical synthesis*
  • Pyrimidines / pharmacology*
  • Tubulin / drug effects
  • Tubulin Modulators
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Indicators and Reagents
  • Pyrazoles
  • Pyrimidines
  • Tubulin
  • Tubulin Modulators
  • Colchicine