Synthesis of caffeic acid amides bearing 2,3,4,5-tetra-hydrobenzo[b][1,4]dioxocine moieties and their biological evaluation as antitumor agents

Molecules. 2014 Jun 3;19(6):7269-86. doi: 10.3390/molecules19067269.

Abstract

A series of caffeic acid amides D1-D17 bearing 2,3,4,5-tetrahydrobenzo-[b][1,4]dioxocine units has been synthesized and their biological activities evaluated for potential antiproliferative and EGFR inhibitory activity. Of all the compounds studied, compound D9 showed the most potent inhibitory activity (IC50=0.79 μM for HepG2 and IC50=0.36 μM for EGFR). The structures of compounds were confirmed by 1H-NMR, ESI-MS and elemental analysis. Among all, the structure of compound D9 ((E)-N-(4-ethoxyphenyl)-3-(2,3,4,5-tetrahydrobenzo[b][1,4]dioxocin-8-yl)acrylamide) was also determined by single-crystal X-ray diffraction analysis. Compound D9 was found to be a potential antitumor agent according to biological activity, molecular docking, apoptosis assay and inhibition of HepG2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amides / chemistry*
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Caffeic Acids / chemistry*
  • Cell Movement / drug effects
  • Drug Screening Assays, Antitumor
  • ErbB Receptors / metabolism
  • Hep G2 Cells
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship
  • X-Ray Diffraction

Substances

  • Amides
  • Antineoplastic Agents
  • Caffeic Acids
  • EGFR protein, human
  • ErbB Receptors
  • caffeic acid