title: 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.affiliation: College of Pharmacy, Shandong University, Ji'nan, Shandong Province 250012, PR China.
authors.forename: Guisen
authors.initials: G
authors.lastname: Zhao
authors.forename: Chuan
authors.initials: C
authors.lastname: Liu
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Dandan
authors.initials: D
authors.lastname: Song
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Wang
authors.forename: Hongxiang
authors.initials: H
authors.lastname: Lou
authors.forename: Yongkui
authors.initials: Y
authors.lastname: Jing
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002855:Chromatography, Thin Layer; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D004976:Ethacrynic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D051549:Glutathione S-Transferase pi / Q000037:antagonists & inhibitors*; D018922:HL-60 Cells; D006801:Humans; D007938:Leukemia / Q000188:drug therapy*; D009682:Magnetic Resonance Spectroscopy; D013055:Spectrophotometry, Infrared; D017550:Spectroscopy, Fourier Transform Infrared; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D051549:Glutathione S-Transferase pi; D004976:Ethacrynic Acid