title: Antitumor activity of S-(p-bromobenzyl)glutathione diesters in vitro: a structure-activity study.
abstract: S-(p-Bromobenzyl)glutathione is a competitive inhibitor of human glyoxalase I which is part of the cytosolic glyoxalase system. It may be delivered into the cystosol of cells by diesterification wherein it is deesterified by cytosolic nonspecific esterases. S-(p-Bromobenzyl)glutathione diesters had antitumor activity in vitro and in vivo. The inhibition of human leukemia 60 cell growth in vitro by a series of alkyl and cycloalkyl diesters of S-(p-bromobenzyl)glutathione was investigated. For n-alkyl diesters, the n-propyl diester was the most potent derivative with a median growth inhibitory concentration GC50 value of 7.77 +/- 0.01 microM (N = 18). The most potent derivative was S-(p-bromobenzyl)glutathione cyclopentyl diester which had a GC50 value of 4.23 +/- 0.01 microM (N = 21) and also had antitumor activity in vivo.
authors.affiliation: Department of Biological and Chemical Sciences, University of Essex, Colchester, U.K.
authors.forename: P J
authors.initials: PJ
authors.lastname: Thornalley
authors.forename: M J
authors.initials: MJ
authors.lastname: Ladan
authors.forename: S J
authors.initials: SJ
authors.lastname: Ridgway
authors.forename: Y
authors.initials: Y
authors.lastname: Kang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004952:Esters; D005978:Glutathione / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D018922:HL-60 Cells; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000037:antagonists & inhibitors; D009682:Magnetic Resonance Spectroscopy; D012044:Regression Analysis; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D004952:Esters; D007791:Lactoylglutathione Lyase; D005978:Glutathione