Synthesis and assessment of the antioxidant and antitumor properties of asymmetric curcumin analogues

Eur J Med Chem. 2015 Mar 26;93:461-9. doi: 10.1016/j.ejmech.2015.02.005. Epub 2015 Feb 7.

Abstract

In this study, 12 asymmetric curcumin (CUR) analogues and 5 symmetric curcumin derivatives were synthesized, the antioxidant activity of these derivatives were evaluated by radicals 1,1-diphenyl-2-picryl-hydrazyl (DPPH) assay, 2,2-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid) (ABTS) assay, ROO (TRAP) assay and O(2-) (NET) assay and anti-proliferative activities of these analogues were assessed against the human hepatoma cell line (SMMC-7721), the human breast cancer cell line (MCF-7) and the human prostate cancer cell lines (PC-3). Most of the asymmetric compounds showed stronger antioxidant activities than Vitamin C (Vc). Curcumin analogues reducing free radicals contain two reaction mechanisms: H-atom and electron transfer mechanisms. Compound 14 showed the most significant antioxidant activity compared with curcumin and other derivatives. Shorted the carbon chain of 14 can reduce the O-H bond dissociation enthalpy (BED) to improve the antioxidant activity. The antioxidant activity of 25 was similar to curcumin. All of the compounds performed better in an anti-proliferate assay than curcumin, especially compound 25, which exhibited the preferential cytotoxic activity against MCF-7 cells(25, IC50 = 9.11 μM, curcumin, IC50 = 70.2 μM). Considering these data, future studies should be performed to assess the therapeutic values of these asymmetric curcumin analogues.

Keywords: Anti-proliferate; Antioxidant; Asymmetric curcumin analogues.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chemistry Techniques, Synthetic
  • Curcumin / analogs & derivatives
  • Curcumin / chemical synthesis*
  • Curcumin / pharmacology*
  • Free Radical Scavengers / chemical synthesis*
  • Free Radical Scavengers / chemistry
  • Free Radical Scavengers / pharmacology*
  • Humans
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Free Radical Scavengers
  • Curcumin