Synthesis and anticancer activity of N-substituted 2-arylquinazolinones bearing trans-stilbene scaffold

Eur J Med Chem. 2015 May 5:95:492-9. doi: 10.1016/j.ejmech.2015.03.057. Epub 2015 Mar 26.

Abstract

A novel series of 2-arylquinazolinones 7a-o bearing trans-stilbene moiety were designed, synthesized, and evaluated against human breast cancer cell lines including human breast adenocarcinoma (MCF-7 and MDA-MB-231) and human ductal breast epithelial tumor (T-47D). Among the tested compounds, the sec-butyl derivative 7h showed the best profile of activity (IC50 < 5 μM) against all cell lines, being 2-fold more potent than standard drug, etoposide. Our investigation revealed that the cytotoxic activity was significantly affected by N3-alkyl substituents. Furthermore, the morphological analysis by acridine orange/ethidium bromide double staining test and flow cytometry analysis indicated that the prototype compound 7h can induce apoptosis in MCF-7 and MDA-MB-231 cells.

Keywords: 3H-quinazolin-4-one; Anti-cancer; Cytotoxic agents; trans-stilbene.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Chemistry Techniques, Synthetic
  • Drug Screening Assays, Antitumor
  • Humans
  • MCF-7 Cells
  • Quinazolinones / chemical synthesis*
  • Quinazolinones / chemistry
  • Quinazolinones / pharmacology*
  • Stereoisomerism
  • Stilbenes / chemistry*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Quinazolinones
  • Stilbenes