Synthesis of trans-caffeate analogues and their bioactivities against HIV-1 integrase and cancer cell lines

Bioorg Med Chem Lett. 2008 Dec 15;18(24):6553-7. doi: 10.1016/j.bmcl.2008.10.046. Epub 2008 Oct 15.

Abstract

Forty caffeate analogues were synthesized via a convenient method starting from vanillin with moderate to good yields. The testing of biological activity of these compounds against HIV-1 integrase indicates that four compounds: bornyl caffeate, bornyl 2-nitrocaffeate, 5-nitrocaffeic acid and 5-nitrocaffeic acid phenethyl ester (5-nitroCAPE) possess a good HIV integrase inhibitory activity, IC(50) 19.9, 26.8, 25.0 and 13.5 microM , respectively. Twelve caffeate analogues were tested by MTT assay on growth of human hepatocellular carcinoma BEL-7404, human breast MCF-7 adenocarcinoma, human lung A549 adenocarcinoma and human gastric cancer BCG823 cell lines, respectively. And the best result is IC(50) 5.5 microM for CAPE against BEL-7404.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology
  • Binding Sites
  • Biotin / chemistry
  • Caffeic Acids / chemistry*
  • Cell Line, Tumor
  • Chemistry, Pharmaceutical / methods
  • Drug Design
  • Enzyme-Linked Immunosorbent Assay
  • HIV Integrase / chemistry*
  • HIV Integrase Inhibitors / chemical synthesis*
  • HIV Integrase Inhibitors / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Models, Chemical
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Caffeic Acids
  • HIV Integrase Inhibitors
  • Biotin
  • HIV Integrase
  • p31 integrase protein, Human immunodeficiency virus 1