Structure-Activity Relationships of the Antitumor C5-Curcuminoid GO-Y030

Molecules. 2015 Aug 24;20(8):15374-91. doi: 10.3390/molecules200815374.

Abstract

1,5-Bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadiene-3-one (2) was isolated from Curcuma domestica as a curcumin (1)-related compound, which we named C5-curcumin. Intrigued by the potent antitumor activity of C5-curcumin (2)-related 1,5-bisaryl-1,4-pentadiene-3-ones [bis(arylmethylidene)acetones, termed C5-curcuminoids], we previously conducted a structure-activity relationship study of C5-curcuminoids and showed that highly active GO-Y030 [1,5-bis(3,5-bis(methoxymethoxy)phenyl)-1,4-pentadiene-3-one (4)] is the most promising antitumor compound. In this study, a panel of C5-curcuminoids based on GO-Y030, consisting of 30 new and 10 known compounds, was synthesized to elucidate in detail which moiety of GO-Y030 is significant for antitumor activity. The results confirmed that both the cross-conjugated dienone moiety and the 3,5-bis(methoxymethoxy) substituent are important for the antitumor activity.

Keywords: Michael reaction; antitumor; curcumin; structure-activity relationship.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Benzene Derivatives / chemical synthesis
  • Benzene Derivatives / chemistry*
  • Benzene Derivatives / pharmacology*
  • Curcumin / chemical synthesis
  • Curcumin / chemistry*
  • Curcumin / pharmacology*
  • Electrons
  • Ketones / chemical synthesis
  • Ketones / chemistry*
  • Ketones / pharmacology*
  • Protons
  • Structure-Activity Relationship

Substances

  • 1,5-bis(3,5-bis(methoxymethoxy)phenyl)penta-1,4-dien-3-one
  • Antineoplastic Agents
  • Benzene Derivatives
  • Ketones
  • Protons
  • Curcumin