Synthesis and mechanistic aspects of 2-anilinonicotinyl-pyrazolo[1,5-a]pyrimidine conjugates that regulate cell proliferation in MCF-7 cells via estrogen signaling

Bioorg Med Chem Lett. 2016 Apr 15;26(8):2077-83. doi: 10.1016/j.bmcl.2016.02.072. Epub 2016 Feb 26.

Abstract

A series of anilinonicotinyl linked pyrazolo[1,5-a]pyrimidine conjugates (6a-x) were synthesized and evaluated for their antiproliferative activity. Some of these conjugates exhibited promising cytotoxic effects in the MCF-7 cell line and among these 6a and 6c exhibited significant effects, apart from G2/M cell cycle arrest. Interestingly they showed profound effects on cyclin D1, Bcl-2 and survivin proteins that regulate breast cancer cell proliferation. Moreover, ER alpha protein expression was studied to understand regulatory role of these conjugates on estrogen activity in estrogen positive breast cancer cells like MCF-7 and compounds 6a and 6c reduced their activity.

Keywords: Bcl-2; Cell cycle; Cyclin D1; Estrogen receptors; Pyrazolopyrimidine.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Cycle / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Estrogens / metabolism*
  • Humans
  • MCF-7 Cells
  • Molecular Structure
  • Nicotine / analogs & derivatives*
  • Nicotine / chemical synthesis
  • Nicotine / chemistry
  • Nicotine / pharmacology
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology*
  • Signal Transduction / drug effects*
  • Structure-Activity Relationship

Substances

  • 2-anilinonicotinyl-pyrazolo(1,5-a)pyrimidine
  • Antineoplastic Agents
  • Estrogens
  • Pyrimidines
  • Nicotine