A novel [1,2,4] triazolo [1,5-a] pyrimidine-based phenyl-linked steroid dimer: synthesis and its cytotoxic activity

Eur J Med Chem. 2013 Nov:69:323-30. doi: 10.1016/j.ejmech.2013.08.029. Epub 2013 Sep 4.

Abstract

A novel [1,2,4] triazolo [1,5-a] pyrimidine-based phenyl-linked steroid dimer was designed, synthesized and evaluated for its cytotoxic activity against five human cancer cell lines and the cytotoxicity against human normal liver cell L-02. Compound 3 showed excellent cytotoxic activity and good selectivity between cancer and normal cells. Further mechanistic studies revealed that treatment of EC109 cells with compound 3 caused an obvious G2/M arrest in a concentration- and time-dependent manner and induced apoptosis probably through the mitochondrial pathway accompanied with the decrease of mitochondrial membrane potential, activations of caspase-9/-3, cleavage of MDM2 as well as up-regulation of the expressions of p53 and Bax.

Keywords: Apoptosis; Cell cycle arrest; Cytotoxicity; Mitochondrial pathway; Steroid dimer; [1,2,4] Triazolo [1,5-a] pyrimidine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cell Cycle / drug effects
  • Cell Line
  • Cell Proliferation / drug effects
  • Dimerization
  • Drug Screening Assays, Antitumor
  • Humans
  • MCF-7 Cells
  • Molecular Structure
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Steroids / chemical synthesis
  • Steroids / chemistry
  • Steroids / pharmacology*
  • Triazoles / chemical synthesis
  • Triazoles / chemistry
  • Triazoles / pharmacology*

Substances

  • 1,2,4-triazole(1,5a)pyrimidine
  • Antineoplastic Agents
  • Pyrimidines
  • Steroids
  • Triazoles