Synthesis of kojic acid-derived copper-chelating apoptosis inducing agents

Yu Hua Chen, Pei Jung Lu, Christopher Hulme, Arthur Y. Shaw

Research output: Contribution to journalArticlepeer-review

23 Scopus citations


Three classes of kojic acid derivatives were synthesized and examined for their antiproliferative activity against HeLa cells. Both 8b and 11 co-treated with copper ion exhibited synergistic effect on the HeLa cell growth inhibition with GI50 values of 11.9 and 7.1 μM, respectively. Flow cytometric analysis of HeLa cells revealed that 11-Cu co-treatment induced the sub-G1 arrest in a dose-dependent manner, suggesting that the growth-inhibitory effect is attributed to DNA fragmentation. Moreover, western blot of HeLa cells cytosolic extracts displayed the cleavage of the 116-kDa protein poly(ADP-ribose) polymerase and activation of caspase-3 by the reduced level of the 32-kDa proenzyme, indicating that the caspase-dependent apoptotic pathway was involved. We further demonstrated that MAPK pathway regulators such as ERK and p38 were activated in response to 11-Cu co-treatment, suggesting that the intracellular oxidative stress was dramatically stimulated by the copper ion. Taken together, we have successfully synthesized kojic acid-derived copper-induced apoptotic agents.

Original languageEnglish (US)
Pages (from-to)995-1003
Number of pages9
JournalMedicinal Chemistry Research
Issue number2
StatePublished - Feb 2013


  • Apoptosis inducing agents
  • Copper-chelating effect
  • Kojic acid
  • Mitogen-activated protein (MAP) kinases

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Organic Chemistry


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