Synthesis and Evaluation of Bakuchiol Derivatives as Potential Anticancer Agents

Molecules. 2018 Feb 26;23(3):515. doi: 10.3390/molecules23030515.

Abstract

A series of bakuchiol derivatives were synthesized and evaluated for their anti-proliferative and the inhibitory activities on SMMC7721 cell line migration using PX-478 as a positive control. The results showed (S,E)-4-(7-methoxy-3,7-dimethyl-3-vinyloct-1-en-1-yl)phenol (10) to have the best activity among the tested compounds, which included PX-478. In addition, compound 10 showed greater inhibitory activity than that of bakuchiol in the transwell migration and invasion assays at every dose. In western blotting tests, compound 10 showed a promising ability to downregulate the expression of HIF-1α and its associated downstream proteins MMP-2 and MMP-9. Moreover, this effect was dose-dependent and could represent a possible mechanism of action for the anticancer activity of compound 10.

Keywords: bakuchiol derivatives; cytotoxicity; invasion; migration; semi-synthesis.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Chemistry Techniques, Synthetic*
  • Dose-Response Relationship, Drug
  • Gene Expression
  • Humans
  • Matrix Metalloproteinase 2 / genetics
  • Matrix Metalloproteinase 2 / metabolism
  • Matrix Metalloproteinase 9 / genetics
  • Matrix Metalloproteinase 9 / metabolism
  • Molecular Structure
  • Phenols / chemical synthesis*
  • Phenols / chemistry
  • Phenols / pharmacology*

Substances

  • Antineoplastic Agents
  • Phenols
  • Matrix Metalloproteinase 2
  • Matrix Metalloproteinase 9
  • bakuchiol