Discovery of novel β-carboline/acylhydrazone hybrids as potent antitumor agents and overcome drug resistance

Eur J Med Chem. 2018 May 25:152:516-526. doi: 10.1016/j.ejmech.2018.05.003. Epub 2018 May 7.

Abstract

Twenty-four novel β-carboline/acylhydrazone hybrids were synthesized and evaluated for their in vitro antiproliferative activity. Among them, 12r exhibited the most potent activity, with IC50 values of 1-2 μM against panel of cancer cell lines and retained significant activity in multidrug resistant cancer cells. Treated cells were not arrested in any phase of cell cycle but resulted in late cellular apoptosis on both MCF-7 and MCF-7/ADR cancer cells. Importantly, 12r showed certain antitumor effect on inhibiting the tumor growth with low toxic and side effects and without significant body weight loss.

Keywords: Antitumor activity; Cellular apoptosis; H460 xenograft model; Multidrug resistance; β-Carboline.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Carbolines / chemistry
  • Carbolines / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Discovery*
  • Drug Resistance, Neoplasm / drug effects*
  • Drug Screening Assays, Antitumor
  • Female
  • Humans
  • Hydrazones / chemistry
  • Hydrazones / pharmacology*
  • Mammary Neoplasms, Experimental
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Molecular Structure
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / pathology
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Carbolines
  • Hydrazones
  • norharman