title: Synthesis and structure-activity relationship of ethacrynic acid analogues on glutathione-s-transferase P1-1 activity inhibition.
abstract: Ethacrynic acid (EA) is a glutathione-s-transferase pi (GSTP1-1) inhibitor. Fifteen of EA analogues were designed and synthesized and their inhibition on GSTP1-1 activity was tested in lysate of human leukemia HL-60 cells. These compounds were synthesized using substituted phenol as precursors through reacting with 2-chlorocarboxylic acid and acylation. Structure-activity analysis indicates that replacements of chlorides of EA by methyl, bromide, and fluoride at 3' position remain the GSTP1-1 inhibitory effect. The compounds without any substitute at 3' position lose the activity on GSTP1-1 inhibition. These data suggest that the substitution of 3' position of EA is necessary for inhibiting GSTP1-1 activity.
authors.affiliation: College of Pharmacy, Shandong University, Ji'nan, Shandong Province, 25001Z, PR China.
authors.forename: Guisen
authors.initials: G
authors.lastname: Zhao
authors.forename: Tao
authors.initials: T
authors.lastname: Yu
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Xiaobing
authors.initials: X
authors.lastname: Wang
authors.forename: Yongkui
authors.initials: Y
authors.lastname: Jing
mesh_terms: D000818:Animals; D002457:Cell Extracts; D045744:Cell Line, Tumor; D015195:Drug Design; D004976:Ethacrynic Acid / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase / Q000037:antagonists & inhibitors* / Q000187:drug effects; D018922:HL-60 Cells; D006219:Halogens; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors* / Q000187:drug effects; D051379:Mice; D008815:Mice, Inbred Strains; D013329:Structure-Activity Relationship; D023041:Xenograft Model Antitumor Assays
chemical_list: D002457:Cell Extracts; D006219:Halogens; D007527:Isoenzymes; C496556:GSTP1 protein, human; D051549:Glutathione S-Transferase pi; D005982:Glutathione Transferase; C496557:Gstp1 protein, mouse; D004976:Ethacrynic Acid