title: [1,2-Bis(2-hydroxyphenyl)ethylenediamine]dichloroplatinum(II), a new compound for the therapy of ovarian cancer. III. Detailed evaluation of the antitumor activity of the enantiomeric complexes on the human NIH:OVCAR-3 ovarian cancer cell line.
abstract: The stereoisomeric [1,2-bis(2-hydroxyphenyl)ethylenediamine]dichloroplatinum(II) complexes were thoroughly tested on the cisplatin-resistant human NIH:OVCAR-3 ovarian cancer cell line. The racemate and its enantiomers produced cytocidal effects at a concentration of 2.5 microM (incubation time 256 h). The meso form, however, was merely cytostatically active. Differences between the enantiomers became evident after a short drug incubation time (1 h) followed by an incubation in drug-free medium (243 h). The S,S-configurated enantiomer (-)-3-PtCl2 proved to be the most active compound. To achieve cytocidal effects concentrations of 2.5-5.0 microM and incubation times of about 3 h were necessary for (-)-3-PtCl2. This compound is also sufficiently stable under test conditions as shown by the preincubation in cell-free medium for 3 h. These results and the augmentation of its antitumor activity by buthionine sulfoximine recommend the further preclinical development of (-)-3-PtCl2 for clinical use.
authors.affiliation: Institut für Pharmazie, Universität Regensburg, Federal Republic of Germany.
authors.forename: G
authors.initials: G
authors.lastname: Bernhardt
authors.forename: R
authors.initials: R
authors.lastname: Gust
authors.forename: H
authors.initials: H
authors.lastname: Reile
authors.forename: H D
authors.initials: HD
authors.lastname: vom Orde
authors.forename: R
authors.initials: R
authors.lastname: Müller
authors.forename: C
authors.initials: C
authors.lastname: Keller
authors.forename: T
authors.initials: T
authors.lastname: Spruss
authors.forename: H
authors.initials: H
authors.lastname: Schönenberger
authors.forename: T
authors.initials: T
authors.lastname: Burgemeister
authors.forename: A
authors.initials: A
authors.lastname: Mannschreck
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D019328:Buthionine Sulfoximine; D002460:Cell Line; D002945:Cisplatin / Q000494:pharmacology; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008717:Methionine Sulfoximine / Q000031:analogs & derivatives / Q000494:pharmacology; D009944:Organoplatinum Compounds / Q000494:pharmacology*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000473:pathology*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds; C073528:(1,2-bis(2-hydroxyphenyl)ethylenediamine)dichloroplatinum (II); D008717:Methionine Sulfoximine; D019328:Buthionine Sulfoximine; D005978:Glutathione; D002945:Cisplatin