Schertl, Sabine and Hartmann, Rolf W. and Batzl-Hartmann, Christine and Bernhardt, Guenther and Spruss, Thilo and Beckenlehner, Karin and Koch, Marion and Krauser, Rudolf and Schlemmer, Richard and Gust, Ronald and Schonenberger, Helmut (2004) [1,2-bis(2,6-difluoro-3-hydroxyphenyl)ethylenediamine]platinum(II) complexes, compounds for the endocrine therapy of breast cancer - Mode of action II: Contribution of drug inactivation, cellular drug uptake and sterical factors in the drug-target interaction to the antitumor activity. ARCHIV DER PHARMAZIE, 337 (6). pp. 349-359. ISSN 0365-6233, 1521-4184
Full text not available from this repository. (Request a copy)Abstract
The marked activity of [meso-1,2-bis(2,6-difluoro-3-hydroxyphenyl)ethylenediamine]platinum(II) (meso-3-PtLL', L,L' = Cl-2 or L = OH2, L' = OSO3) on the hormone-sensitive MXT-M-3,2 breast cancer implanted in mice is most probably due to a mechanism based on the reduction of the endogenous estrogen level. Cytotoxic effects which are poorly pronounced in experiments on several breast cancer cell lines (e.g. MCF-7), do not significantly contribute to the anti-breast cancer activity of this compound. In contrast to this, the standard cisplatin and the structurally related comparison compound [meso-1,2-bis(4-fluorophenyl)ethylenediamine]platinum(II) (meso-4-PtLL', L,L' = Cl-2 or L = OH2, L' = OSO3) are strongly active in vivo as well as in vitro. Both effects entail programmed cell death, which is responsible for the inhibition of the tumor growth. The minor cytotoxicity of meso-3-PtLL' in breast cancer cell cultures is caused neither by an inappropriate rate of reaction with bionucleophiles (e.g. by a too fast inactivation by plasma proteins) nor solely by the observed poor absorption by the tumor cells resulting in an insufficient drug concentration at the DNA. Additionally, an impeded reaction with biologically important, guanine-rich sequences of DNA (owing to the 2,6-standing F atoms which hinder the drug-target interaction) must be assumed as cause of its marginal cytotoxicity.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | DIAQUA(1,2-DIPHENYLETHYLENEDIAMINE) PLATINUM(II) SULFATES; INHIBITING PROPERTIES; ANTICANCER DRUGS; SERUM-ALBUMIN; MAJOR ADDUCT; IN-VITRO; CISPLATIN; DNA; CIS-DIAMMINEDICHLOROPLATINUM(II); CYTOTOXICITY; reactivity; inactivation kinetics; drug accumulation; anti-breast cancer activity |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Alumni or Retired Professors > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 14 Jul 2021 04:51 |
| Last Modified: | 14 Jul 2021 04:51 |
| URI: | https://pred.uni-regensburg.de/id/eprint/37555 |
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