The synthesis of alpha,beta-unsaturated carbonyl derivatives with the ability to inhibit both glutathione S-transferase P1-1 activity and the proliferation of leukemia cells.

Abstract

Ethacrynic acid (EA), an alpha,beta-unsaturated carbonyl compound, is a glutathione S-transferase P1-1 (GSTP1-1) inhibitor. Twenty-one novel EA derivatives have been synthesized. The effects of these compounds on GSTP1-1 activity and on the proliferation of human leukemia HL-60 cells have been determined. Compounds with a halogen substitution at the 3'-position of the aromatic ring have greater inhibitory effects on GSTP1-1 activity than those of compounds with a methyl substitution there. Compounds with substitutions at both the 2'- and 3'-positions of the aromatic ring have more antiproliferative ability than those with one substitution at 3'-position. Esterification of the carboxyl group appears to increase the antiproliferative ability.

• Authors: Guisen Zhao, Chuan Liu, Rui Wang, Dandan Song, Xiaobing Wang, Hongxiang Lou, Yongkui Jing
• Journal: Bioorganic & medicinal chemistry (Bioorg Med Chem) Vol. 15 Issue 7 Pg. 2701-7 (Apr 01 2007) ISSN: 0968-0896 [Print] England
• PMID: 17287120 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antineoplastic Agents
• Enzyme Inhibitors
• Glutathione S-Transferase pi
• Ethacrynic Acid

Topics

• Antineoplastic Agents (chemical synthesis, pharmacology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Chromatography, Thin Layer
• Enzyme Inhibitors (chemical synthesis, pharmacology)
• Ethacrynic Acid (analogs & derivatives, chemical synthesis, pharmacology)
• Glutathione S-Transferase pi (antagonists & inhibitors)
• HL-60 Cells
• Humans
• Leukemia (drug therapy)
• Magnetic Resonance Spectroscopy
• Spectrophotometry, Infrared
• Spectroscopy, Fourier Transform Infrared
• Structure-Activity Relationship