Gust, Ronald and Niebler, Karlheinz and Schoenenberger, Helmut (2005) [N-Ethyl- and [N,N '-diethyl-1,2-bis(2,6-difluoro-3-hydroxyphenyl)-ethylenediamine]dichloroplatinum(II): Structure and cytotoxic/estrogenic activity in breast cancer cells. JOURNAL OF MEDICINAL CHEMISTRY, 48 (23). pp. 7132-7144. ISSN 0022-2623,
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N-Ethyl and N,N'-diethyl derivatives (erythro- and threo-2-PtCl2; meso- and D,L-3-PtCl2) of [meso- and D,L-1,2-bis(2,6-difluoro-3-hydroxyphenyl)ethylenediamine]dichloroplatinum(II) (meso- and D,L-1-PtCl2) were synthesized and tested for cytotoxicity on the estrogen receptor-positive (ER+) human MCF-7 breast cancer cell line. In this test, only D,L-1-PtCl2 and threo2-PtCl2 showed strong cytotoxic properties. This revealed the existence of at least one NH2 fragment as a prerequisite for antitumor activity. Furthermore, studies on the three-dimensional structure of the new compounds demonstrated that the aryl and alkyl residues at the five-membered chelate ring have to be arranged in equatorial positions for the triggering of cytotoxic effects, very likely due to the reaction with d(GpG) sequences in DNA resulting in GG-N7,N7 chelates. A contribution of the ER-mediated processes-(a) hindrance of the cellular processing of Pt-modified DNA by overexpression of high mobility group domain proteins and (b) interruption of the vicious circle of mutual growth stimulation of breast cancer cells and granulocytes/macrophages by reduction of the formation of key cytokines-to the anti-breast cancer activity of threo-2-PtCl2 is unlikely, since we did not observe transcription activation in the test on ER+ MCF-7 breast cancer cells stably transfected with luciferase reporter plasmid ERE(wtc)luc.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | TUMOR-INHIBITING PROPERTIES; BIOLOGICAL RESPONSE MODIFIER; ANTICANCER DRUG CISPLATIN; PLATINUM(II) COMPLEXES; VARIABLE SUBSTITUENTS; ESTROGENIC ACTIVITY; ANTITUMOR-ACTIVITY; 2-PHENYL RING; <1,2-BIS(2,6-DIHALO-3-HYDROXYPHENYL)ETHYLENEDIAMINE>PLATINUM(II) COMPLEXES; ENDOCRINE THERAPY; |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy > Alumni or Retired Professors > Prof. Schönenberger |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 23 Apr 2021 07:00 |
| Last Modified: | 23 Apr 2021 07:00 |
| URI: | https://pred.uni-regensburg.de/id/eprint/35413 |
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