Synthese, in vivo- und in vitro-Untersuchungen zur tumorhemmenden Wirkung von cis-Dichloro-dipeptidester-platin(II)-Komplexen / Synthesis, in vivo and in vitro Studies on the Antineoplastic Effect of cis-Dichloro-dipeptide Ester Platinum(II) Complexes

Abstract

cis-Dichlorodipeptide esterplatinum complexesCl2Pt(MetGlyOEt),Cl2Pt(EthionylGlyOEt), Cl2Pt(GlyGlyOEt)2 and Cl2Pt(GlySerOEt)2 are prepared from the α-amino acid complexes by peptide synthesis using platinum as an amino protecting group. cis-Cl2Pt(GlyGlyOEt)2 and cis-Cl2Pt(GlySerOEt)2 have been prepared also directly from K2PtCl4 and the dipeptidesters. cis-Cl2Pt(GlyGlyOEt)2 (2 a) and cis-Cl2Pt(NH3)2 (5) lead to a prefered inhibition of the DNA-synthesis of sarcoma 180, Yoshida-sarcoma and Walker-256-carcinosarcoma in vitro; RNA- and protein biosynthesis are influenced to a much lower degree. 2a and 5 cause filamentous growth in Escherichia coli B. The DNA polymerase deficient strain of E. coli, p 3478 pol A-, is more inhibited by 2 a and 5 than the non deficient strain W 3110 pol A+. Tumor growth of di-2-chloro-ethylmethylamine (HN2) resistant sarcoma 180 and of Yoshida sarcoma is weakly inhibited, whereas Walker-256-carcinosarcoma is markedly inhibited; however 2a and 5 show similar inhibition of the same tumor.

The first examples of platinum amine hydroxamate complexes: structures and biological activity

“…Attempts to selectively target Pt drugs to tumour cells over healthy cells using biologically active ligands, particularly those that have an affinity for tumour cells or have increased cellular uptake, have not met with great success. [3][4][5] Recent approaches to anticancer therapy have involved agents that target specific cellular processes that are enhanced or altered in tumours. In particular, the discovery of matrix metalloproteinases (MMPs) as enzymes critically linked to metastasising tumours has prompted development of a class of drugs that have the potential to not only be potent, but act selectively on tumours as well.…”

Optimization of cisplatin for the treatment of hormone dependent tumoral diseases

“…One of the first attempts to develop Pt-complexes acting according to this concept was the synthesis and evaluation of several cis-[dipeptidester]dichloroplatinum(II) compounds by Beck et al [35]. It was assumed that the complexes were enriched in tumor cells due to an increased uptake of amino acids, peptides and proteins by the latter.…”

“…[31][32][33][34][35][36][37][38][39] and [61] cited therein). Presumably this effect contributes as well to the anti-breast cancer activity of ER-agonistic or ER-antagonistic Pt-complexes.…”