Mechanism of action of cis-bis(glycylglycineethyl ester)platinum(II) chloride - effect on protein biosynthesis

The effect of cis-bis(glycylglycine Et ester)platinum(II) chloride [60426-60-0] and cisplatinum [15663-27-1] on the protein biosynthesis of Walker-25 carcinosarcoma was confirmed to arise from an inhibition of the aminoacylation of tRNA and the biosynthesis of polyphenylalanine. Expts. were conducted in a cell-free system using poly-U as exogenous messenger

cis-Dichloropeptide ester-platinum(II) complexes

Peptide complexes I (R, R1 = H, C1-4 alkyl, optionally substituted by OH, NH2, OMe, OEt, SH, SMe, SEt, CH2Ph, CH2C6H4OH, CH2C6H4OMe, CH2C6H4OEt; R2 = C1-4 alkyl; n = 1-3) were prepd. Thus cis-PtCl2(Gly-OH)2 was treated with 4-O2NC6H4OH and cis-PtCl2(Gly-OC6H4NO2-4)2 treated with H-Gly-OEt to give cis-PtCl2(Gly-Gly-OEt)2 (I). I had a min. inhibitory concn. against Escherichia coli B of 5 * 10-4 mol/L and inhibited DNA synthesis in Walker 256 carcinosarcoma at 4.5 * 10-7 mol/L

cis-Dichloro[bis(oligopeptide ester)]platinum(II) complexes, study on the detection of antitumor activity with bacteriological test systems

Sixteen title compds., PtA2Cl2 (A = peptide ester groups), and 10 known antitumor compds. were compared in 3 bacteriol. tests: filament induction in Escherichia coli B, growth inhibition of DNA polymerase-deficient E. coli p 3478 pol A-, and prophage induction in E. coli K12 (l). The compds. were also tested for inhibition of ADJ/PC6 plasmacytoma growth in vitro. Only the prophage induction test correlated with the neoplasm-inhibitory activity, suggesting it as a screening method for detecting antineoplastic Pt complexes

Synthesis, in vivo and in vitro studies on the antineoplastic effect of cis-dichloro-dipeptide ester-platinum(II) complexes

Cis-Cl2Pt(GlyGlyOEt)2 (I) [60426-60-0] (1.7 * 10-5M) inhibited DNA formation by sarcoma 180, Yoshida sarcoma, and Walker 256 carcinosarcoma in vitro. RNA and protein synthesis were inhibited to a lesser extent. I inhibited growth of Walker 256 carcinosarcoma by 78% at 380 mg/kg i.p. in rats and produced 30% cures; I was less effective against the other tumors in vivo. I caused filamentous growth of Escherichia coli B. A DNA polymerase-deficient strain of E. coli was more strongly inhibited by I than a nondeficient strain. I was prepd. either (1) directly from K2PtCl4 and the dipeptide ester or (2) from the alpha -amino acid complex using Pt as an amino protecting group. Also prepd. Cl2Pt(MetGlyOEt) (II) [60399-21-5], Cl2Pt(ethynyl-GlyOEt) [60399-23-7], cis-Cl2Pt(GlySerOet)2 [60399-28-2], and some corresponding Pd complexes

Studies on the mammary tumor inhibiting effect of cis-bis(glycylglycin ethyl ester)platinum(II) chloride

In vivo, cis-dichlorodiammineplatinum(II) (I) [15663-27-1] and cis-dichlorobis(glycylglycine Et ester)platinum(II) (II) [60426-60-0] inhibited the DMBA-induced hormone-dependent mammary carcinoma of the SD rat. In vitro, a marked effect on DNA synthesis by mammary tumor cells and an inhibition of estradiol-receptor interaction by I and II were demonstrated. Binding to DNA and inhibition of the proliferation-stimulating effect of endogenous estrogens by blocking the hormone receptors are discussed as modes of action of I and II

Studies on the mechanism activity of cis-bis(glycylglycine ethyl ester)platinum(II) chloride - action on nucleic acid metabolism

cis-bis(glycylglycinethylester)platinum II chloride (I) [60426-60-0] interfered with the nucleic acid metab. in tumor cells by inhibiting the DNA template activity as well as the DNA- [9012-90-2] and RNA polymerase [9014-24-8] and the ribonucleotide reductase [9040-57-7] system. The activity of I was similar to the therapeutically used Pt coordination complex cis-Pt(NH3)2Cl2

Relations between structure and antitumor activity of cis-dichloro[bis(oligopeptide ester)platinum(II)] complexes

Several title compds., cis- and trans-[PtA2X2] complexes (A = esters of oligopeptides; X = Cl, oxalate, or malonate), were tested for their ability to inhibit thymidine 3H incorporation by suspensions by ADJ/PC6 plasmacytoma cells, as an index of antitumor action. The effect was markedly dependent on the type, no., and sequence of the amino acids in the peptide component. The most active compd. was cis-[Pt(Gly-GlyOEt)2Cl2] [60426-60-0], whose activity was comparable with that of mitomycin C, amethopterin, or 5-fluorouracil. The isomeric trans-[Pt(Gly-GlyOEt)2Cl2] [39680-31-4] had insignificant activity. Substitution of other amino acids for the glycyl residue directly coordinated to the Pt markedly decreased antitumor activity, as did replacement of Gly-GlyOEt by Gly-Gly-GlyOEt. There was a close correlation between the ability of the compds. to inhibit thymidine uptake in the above system and their inhibition of ADJ/PC6 plasmacytoma growth in mice. Brief data are also given on the UV difference spectra of DNA after interaction with some of the Pt compds

Metal complexes with biologically important ligands. XXI. Antitumor active cis-platinum(II) complexes with alpha -amino acid esters and peptide esters. Structure of cis-dichlorobis(glycylglycine ethyl ester)platinum(II)

cis-PtX2L2 (X = Cl, Br, I; L = alpha -amino acid ester, peptide ester) and cis-PtZL2 (H2Z = oxalic acid, malonic acid) were prepd. from PtX42- or PtZ22- and L. The dipeptide complexes were also prepd. via peptide synthesis from PtCl2(NH2CHRCO2H)2 and alpha -amino acid esters using carbodiimide as the coupling agent. PtCl2L2 (L = alpha -amino acid ester) were prepd. from cis-Pt(NH2CHRCO)2 and alc. in the presence of HCl. cis-PtCl(GlyGlyOET)2 is triclinic, space group P.hivin.1, with a 887.2(2), b 928.2(3), c 1421.2(5) pm, alpha 78.01(3), beta 82.58(3), gamma 60.24(2) Deg, Z = 2, d. (x-ray) = 1.96