KOCKERBAUER, R and BEDNARSKI, PJ (1995) A NOVEL-APPROACH TO PREPARING WATER-SOLUBLE PRODRUG FORMS OF CISPLATIN ANALOGS BEARING CHELATING DIAMINES. JOURNAL OF PHARMACEUTICAL SCIENCES, 84 (7). pp. 819-823. ISSN 0022-3549,
Full text not available from this repository.Abstract
A novel method for creating water soluble prodrugs of cisplatin analogues bearing chelating diamines is introduced. When 2-(amino-methyl)aniline is reacted with K2PtCl4 between a pH of 6 and 7, the neutral chelated complex [2-(aminomethyl)aniline]dichloroplatinum(II) (1) is isolated. On the other hand, when the complexation occurs under acidic conditions (i.e. pH 3), the zwitterionic, ''open-ring'' form [2-(ammonio-methyl)aniline-N-1]trichloroplatinate(ll) (2) is obtained, whereby only the aniline nitrogen is coordinated to platinum. Compound 2 has a solubility of 10 mM in acidic aqueous medium; that is ca. 20 times greater than that of 1. However, 2 rapidly converts to compound 1 at physiologic pH; thus 2 functions as a water soluble prodrug of 1. Both 1 and 2 are equally effective at halting the growth of three different human cancer cell lines in vitro, indicating that the prodrug is quantitatively converted to the parent drug in a complex, biologically relevant medium. In animal experiments, the prodrug form, when given at a dose of 25 mu mol/kg three times a week for 6 weeks, significantly inhibits the growth of the MXT (M3.2) mammary tumor in BDF mice while the same dose of the parent drug has no antitumor activity.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MIXED-AMINE CISPLATIN; CANCER-CHEMOTHERAPY; PLATINUM COMPLEXES; AQUEOUS CHEMISTRY; ETHYLENEDIAMINE; |
| Depositing User: | Dr. Gernot Deinzer |
| Last Modified: | 19 Oct 2022 08:37 |
| URI: | https://pred.uni-regensburg.de/id/eprint/52462 |
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