Synthesis of imine-pyrazolopyrimidinones and their mechanistic interventions on anticancer activity

Bioorg Med Chem. 2013 Sep 15;21(18):5782-93. doi: 10.1016/j.bmc.2013.07.016. Epub 2013 Jul 17.

Abstract

Design, synthesis and anticancer activity of a series of imine-pyrazolopyrimidinones is reported for the first time. Compounds 9d, 9n and 9o in the series show encouraging in vitro anticancer activity with low micromolar IC50 values against prostate (PC3) and breast (MCF7) cancer cell lines. Some notions about structure-activity relationships and plausible mechanism of biological activity are presented.

Keywords: Anticancer agents; Catalytic topoisomerase inhibitors; Effects on G2/M phase of the cell cycle; Imine-pyrazolopyrimidinones; Synthesis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antigens, Neoplasm / chemistry
  • Antigens, Neoplasm / metabolism
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / toxicity
  • Binding Sites
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • DNA Topoisomerases, Type II / chemistry
  • DNA Topoisomerases, Type II / metabolism
  • DNA-Binding Proteins / chemistry
  • DNA-Binding Proteins / metabolism
  • Drug Design
  • Drug Screening Assays, Antitumor
  • G2 Phase Cell Cycle Checkpoints / drug effects
  • HeLa Cells
  • Humans
  • Imines / chemistry*
  • M Phase Cell Cycle Checkpoints / drug effects
  • MCF-7 Cells
  • Molecular Docking Simulation
  • Protein Structure, Tertiary
  • Pyrazoles / chemical synthesis
  • Pyrazoles / chemistry*
  • Pyrazoles / toxicity
  • Pyridines / chemical synthesis
  • Pyridines / chemistry*
  • Pyridines / toxicity
  • Structure-Activity Relationship

Substances

  • Antigens, Neoplasm
  • Antineoplastic Agents
  • DNA-Binding Proteins
  • Imines
  • Pyrazoles
  • Pyridines
  • pyrazolopyridine
  • DNA Topoisomerases, Type II