Anticancer phytochemical analogs 37: synthesis, characterization, molecular docking and cytotoxicity of novel plumbagin hydrazones against breast cancer cells

Bioorg Med Chem Lett. 2014 Jul 1;24(13):2900-4. doi: 10.1016/j.bmcl.2014.04.100. Epub 2014 May 4.

Abstract

We have synthesized, structurally characterized and examined cytotoxicity of novel plumbagin hydrazones against estrogen and progesterone receptor positive (ER+/PR+) MCF-7 and triple negative MDA-MB-231 breast cancer cell lines in order to evaluate the potential of these novel phytochemical analogs. Compounds were docked into the protein cavity of p50-subunit of NF-κB protein revealing better fit and better binding energies than the parent plumbagin compound. This was also reflected in their superior cytotoxicities which were found to be mediated by inhibition of NF-κB expression. These compounds can provide a starting point for the development of novel drug molecules against triple negative breast cancers.

Keywords: Breast cancer; Molecular docking; NF-κB; Plumbagin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / pathology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Hydrazones / chemical synthesis
  • Hydrazones / chemistry
  • Hydrazones / pharmacology*
  • MCF-7 Cells
  • Models, Molecular
  • Molecular Structure
  • Naphthoquinones / chemical synthesis
  • Naphthoquinones / chemistry
  • Naphthoquinones / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Hydrazones
  • Naphthoquinones
  • plumbagin