Radical-scavenging activity and cytotoxicity of p-methoxyphenol and p-cresol dimers

Molecules. 2010 Feb 26;15(3):1103-12. doi: 10.3390/molecules15031103.


Compoundswith two phenolic OH groups like curcumin possess efficient antioxidant and anti-inflammatory activity. We synthesized p-cresol dimer (2,2'-dihydroxy-5,5'-dimethylbiphenol, 2a) and p-methoxyphenol dimer (2,2'-dihydroxy-5,5'-dimethoxybiphenol, 2b) by ortho-ortho coupling reactions of the parent monomers, p-cresol (1a) and p-methoxyphenol (1b), respectively. Their antioxidant activity was determined using the induction period method, and their cytotoxicity towards RAW 264.7 cells was also investigated using a cell counting kit. The stoichiometric factors n (number of free radicals trapped by one mole of antioxidant moiety) for 2a and 2b were 3 and 2.8, respectively, being greater than those for 1a and 1b. The ratio of the rate constant of inhibition to that of propagation (k(inh)/k(p)) for 2a and 2b was similar to that for 2-t-butyl-4-methoxyphenol (BHA), a conventional food antioxidant. The 50% inhibitory dose (ID50) declined in the order 1b > 1a >> 2b > 2a > BHA. The cytotoxicity for 2a and 2b was significantly greater than that for the parent monomers (p < 0.001), but smaller than that for BHA (p < 0.01). Compounds 2a and 2b may be useful as food antioxidants.

MeSH terms

  • Animals
  • Anisoles / chemistry
  • Anisoles / pharmacology*
  • Calorimetry, Differential Scanning
  • Cell Line
  • Cell Survival / drug effects
  • Cresols / chemistry
  • Cresols / pharmacology*
  • Dimerization
  • Dose-Response Relationship, Drug
  • Free Radical Scavengers / chemistry
  • Free Radical Scavengers / pharmacology*
  • Macrophages / cytology
  • Macrophages / drug effects
  • Magnetic Resonance Spectroscopy
  • Mice


  • Anisoles
  • Cresols
  • Free Radical Scavengers
  • 4-cresol
  • mequinol