In vivo and in silico anti-inflammatory mechanism of action of the semisynthetic (-)-cubebin derivatives (-)-hinokinin and (-)-O-benzylcubebin

Bioorg Med Chem Lett. 2017 Jan 15;27(2):176-179. doi: 10.1016/j.bmcl.2016.11.081. Epub 2016 Nov 29.

Abstract

(-)-Cubebin (CUB), isolated from seeds of Piper cubeba, was used as starting material to obtain the derivatives (-)-hinokinin (HK) and (-)-O-benzyl cubebin (OBZ). Using paw edema as the experimental model and different chemical mediators (prostaglandin and dextran), it was observed that both derivatives were active in comparison with both negative (5% Tween® 80 in saline) and positive (indomethacin) controls. The highest reduction in the prostaglandin-induced edema was achieved by OBZ (66.0%), while HK caused a 59.2% reduction. Nonetheless, the dextran-induced paw edema was not significantly reduced by either of the derivatives (HK or OBZ), which inhibited edema formation by 18.3% and 3.5%, respectively, in contrast with the positive control, cyproheptadine, which reduced the edema by 56.0%. The docking analysis showed that OBZ presented the most stable ligand-receptor (COX-2 - cyclooxygenase-2) interaction in comparison with CUB and HK.

Keywords: (−)-Cubebin; (−)-Hinokinin; (−)-O-benzylcubebin; Anti-inflammatory activity; Piper cubeba.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / administration & dosage
  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / chemical synthesis
  • 4-Butyrolactone / chemistry
  • 4-Butyrolactone / pharmacology
  • Animals
  • Anti-Inflammatory Agents, Non-Steroidal / administration & dosage
  • Anti-Inflammatory Agents, Non-Steroidal / chemical synthesis
  • Anti-Inflammatory Agents, Non-Steroidal / chemistry
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Benzodioxoles / administration & dosage
  • Benzodioxoles / chemical synthesis
  • Benzodioxoles / chemistry
  • Benzodioxoles / pharmacology*
  • Catalytic Domain
  • Computer Simulation
  • Cyclooxygenase 2 / chemistry
  • Cyclooxygenase 2 Inhibitors / administration & dosage
  • Cyclooxygenase 2 Inhibitors / chemical synthesis
  • Cyclooxygenase 2 Inhibitors / chemistry
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Cyproheptadine / pharmacology
  • Dextrans / pharmacology
  • Dinoprostone / pharmacology
  • Dioxoles / administration & dosage
  • Dioxoles / chemical synthesis
  • Dioxoles / chemistry
  • Dioxoles / pharmacology*
  • Edema / chemically induced
  • Furans / administration & dosage
  • Furans / chemical synthesis
  • Furans / chemistry
  • Furans / pharmacology*
  • Indomethacin / pharmacology
  • Ligands
  • Lignans / administration & dosage
  • Lignans / chemical synthesis
  • Lignans / chemistry
  • Lignans / isolation & purification
  • Lignans / pharmacology*
  • Male
  • Mice
  • Molecular Docking Simulation
  • Polysorbates / pharmacology
  • Rats, Wistar
  • Rutaceae / chemistry

Substances

  • Anti-Inflammatory Agents, Non-Steroidal
  • Benzodioxoles
  • Cyclooxygenase 2 Inhibitors
  • Dextrans
  • Dioxoles
  • Furans
  • Ligands
  • Lignans
  • Polysorbates
  • o-benzyl cubebin
  • hinokinin
  • Cyproheptadine
  • Ptgs2 protein, mouse
  • Cyclooxygenase 2
  • cubebin
  • Dinoprostone
  • 4-Butyrolactone
  • Indomethacin