Synthesis of novel flavone derivatives possessing substituted benzamides and their biological evaluation against human cancer cells

Bioorg Med Chem Lett. 2016 Sep 1;26(17):4170-3. doi: 10.1016/j.bmcl.2016.07.063. Epub 2016 Jul 28.

Abstract

Baicalein is a well-known flavone derivative that possesses diverse biological properties, such as anticancer, antioxidant and anti-inflammatory activities. Numerous baicalein derivatives, including 5,6,7-trimethoxyflavone, have been synthesized with the aim of enhancing its inherent biological activities. In the present work, new flavones, possessing an N-aroylamine-substituent on the B-ring, were synthesized to improve the cytotoxicity of baicalein and 5,6,7-trimethoxyflavone against human cancer cell lines. The majority of the flavones synthesized exhibited greater cytotoxicity than baicalein and 5,6,7-trimethoxyflavone against HepG2 and MCF-7 cells. Among them, compounds 5n, possessing a 3-methoxybenzoylamino group, exhibited great cytotoxic effects on HepG2 (GI50=7.06μM) and MCF-7 (GI50=7.67μM) cells. In contrast, N-aroylamine-substituted 5-hydroxy-6,7-dimethoxyflavone derivatives showed greater cytotoxicity against MCF-7 than HepG2 cells, indicating that the replacement of a 5-methoxy group on the A-ring with a 5-hydroxy group has a marked influence on the cytotoxicity profile.

Keywords: 5,6,7-Trimethoxyflavone; Baicalein; Cytotoxicity; HepG2; MCF-7; N-Aroylamine-substituted.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / toxicity
  • Benzamides / chemistry*
  • Cell Survival / drug effects
  • Flavanones / chemistry
  • Flavones / chemical synthesis
  • Flavones / chemistry*
  • Flavones / toxicity
  • Flavonoids / chemistry
  • Flavonoids / toxicity
  • Hep G2 Cells
  • Humans
  • MCF-7 Cells
  • Neoplasms
  • Structure-Activity Relationship

Substances

  • 5,6,7-trimethoxyflavone
  • Antineoplastic Agents
  • Benzamides
  • Flavanones
  • Flavones
  • Flavonoids
  • baicalein