Synthesis and biological evaluation of 3',4',5'-trimethoxychalcone analogues as inhibitors of nitric oxide production and tumor cell proliferation

Bioorg Med Chem. 2009 Dec 1;17(23):7909-14. doi: 10.1016/j.bmc.2009.10.022. Epub 2009 Oct 28.

Abstract

A series of 23 3',4',5'-trimethoxychalcone analogues was synthesized and their inhibitory effects on nitric oxide (NO) production in LPS/IFN-gamma-treated macrophages, and tumor cell proliferation has been investigated. 4-Hydroxy-3,3',4',5'-tetramethoxychalcone (7), 3,4-dihydroxy-3',4',5'-trimethoxychalcone (11), 3-hydroxy-3',4,4',5'-tetramethoxychalcone (14), and 3,3',4',5'-tetramethoxychalcone (15) were the most potent growth inhibitory agents on NO production, with an IC(50) value of 0.3, 1.5, 1.3 and 0.3 microM, respectively. The tumor cells proliferation assay results revealed that several compounds exhibited potent inhibition activity against different cancer cell lines. The chalcone 15 was the most potent anti-proliferative compound in the series with IC(50) values of 1.8 and 2.2 microM toward liver cancer Hep G2 and colon cancer Colon 205 cell lines, respectively. 2,3,3',4',5'-Pentamethoxychalcone (1), 3,3',4,4',5,5'-hexamethoxychalcone (3), 2,3',4,4',5,5'-hexamethoxychalcone (5), 2-hydroxy-3,3',4',5'-tetramethoxychalcone (10), 11 and 14 showed significant anti-proliferation actions in Hep G2 and Colon 205 cells with an IC(50) values ranging between 10 and 20 microM. Among the tested agents, compound 7 showed selective NO production inhibition (IC(50)=0.3 microM), while has no effect on tumor cell proliferation (IC(50) >100 microM). 3,3',4,4',5'-Pentamethoxychalcone (2) showed selective anti-proliferation effect in Hep G2 cells, in addition to its potent NO inhibition, however has no such response in Colon 205 cells. In contrast, 3-formyl-3',4',5'-trimethoxychalcone (22) showed moderate growth inhibition in Colon 205 cells, while has no such effect on NO production and Hep G2 cells proliferation. These results provide insight into the correlation between some structural properties of 3',4',5'-trimethoxychalcones and their in vitro anti-inflammatory and anti-cancer differentiation activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anti-Inflammatory Agents / chemical synthesis*
  • Anti-Inflammatory Agents / chemistry
  • Anti-Inflammatory Agents / pharmacology
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Proliferation / drug effects
  • Chalcones / chemical synthesis*
  • Chalcones / chemistry
  • Chalcones / pharmacology*
  • Hep G2 Cells
  • Humans
  • Inhibitory Concentration 50
  • Macrophage Activation / drug effects
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Magnetic Resonance Spectroscopy
  • Mice
  • Nitric Oxide / antagonists & inhibitors*
  • Nitric Oxide / biosynthesis
  • Spectrometry, Mass, Electrospray Ionization

Substances

  • Anti-Inflammatory Agents
  • Antineoplastic Agents
  • Chalcones
  • Nitric Oxide