Fluorocurcumins as cyclooxygenase-2 inhibitor: molecular docking, pharmacokinetics and tissue distribution in mice

Pharm Res. 2009 Nov;26(11):2438-45. doi: 10.1007/s11095-009-9955-6. Epub 2009 Aug 28.


Purpose: The purpose of the current study was to assess the effect of newly synthesized Curcumin analogs on COX-2 protein by molecular docking studies and by assessments of the effect of one such analog (CDF) on nuclear factor NF-kappaB and PGE(2). In addition, we have determined the pharmacokinetics and tissue distribution of CDF in mice compared to Curcumin.

Methods: Molecular docking on COX-2 protein was assessed by standard computer modeling studies. PGE(2) assay in conditioned media was done utilizing high sensitivity immunoassay kit following manufacturer's instructions, while NF-kappaB was done by routine EMSA. Serum pharmacokinetics and tissue distribution studies were carried out using the validated high-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS) methods.

Results: The molecular docking showed that fluorocurcumin analogs do not introduce any major steric changes compared to the parent Curcumin molecule, which was consistent with down-regulation of NF-kappaB and reduced PGE(2) levels in cells treated with CDF. Pharmacokinetic parameters revealed that CDF had better retention and bioavailability and that the concentration of CDF in the pancreas tissue was 10-fold higher compared to Curcumin.

Conclusion: Our observations clearly suggest that the bioavailability of CDF is much superior compared to Curcumin, suggesting that CDF would be clinically useful.

MeSH terms

  • Animals
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacokinetics
  • Antineoplastic Agents / therapeutic use
  • Cell Line, Tumor
  • Chromatography, High Pressure Liquid
  • Curcumin / analogs & derivatives*
  • Curcumin / chemistry
  • Curcumin / pharmacokinetics*
  • Curcumin / therapeutic use
  • Cyclooxygenase 2 / chemistry
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase 2 Inhibitors / chemistry*
  • Cyclooxygenase 2 Inhibitors / metabolism
  • Cyclooxygenase 2 Inhibitors / pharmacokinetics*
  • Cyclooxygenase 2 Inhibitors / therapeutic use
  • Female
  • Humans
  • Mice
  • Mice, SCID
  • Models, Molecular*
  • Pancreatic Neoplasms / drug therapy
  • Tissue Distribution


  • Antineoplastic Agents
  • Cyclooxygenase 2 Inhibitors
  • Cyclooxygenase 2
  • Curcumin