Novel alkyl-1,4-butanediamine Pt(II) complexes having a seven-membered ring structure were synthesized and characterized by fast atom bombardment mass and infrared spectra and elemental analysis. Their antitumor activities in vivo toward lymphoid leukemia L1210 and Lewis lung carcinoma LL were studied in the case where the leaving group was either dichloride or cyclobutane-1,1-dicarboxylate. 1,4-Butanediamine Pt(II) complexes (seven-membered ring) showed higher antitumor activities than those of ethylenediamine Pt(II) (five-membered ring) and 1,3-propanediamine Pt(II) (six-membered ring) complexes toward L1210 for both leaving groups. Alkyl-1,4-butanediamine Pt(II) complexes showed high antitumor activities toward L1210, except for 1,1-dimethyl-1,4-butanediamine Pt(II) complexes. In particular, 2,2-dimethyl-1,4-butanediamine and 2,3-dimethyl-1,4-butanediamine Pt(II) complexes exhibited excellent antitumor activities with T/C% values higher than 300. None of the dichloro Pt(II) complexes showed antitumor activities toward LL, but the cyclobutane-1,1-dicarboxylato Pt(II) complexes, which were moderately active toward L1210 with T/C% values around 200, also showed high antitumor activities toward LL with T/C% values of more than 200. Alkyl-1,4-butanediamine Pt(II) complexes with a seven-membered ring structure were found to be stable and to have antitumor activities in vivo.
Factor analysis was applied to the data matrix of in vitro growth inhibitory activities of 52 platinum complexes against 9 tumor cell lines, L1210, P388, Lewis lung, AH66, AH66F, HeLa S3, KB, HT-1197 and HT-1376 cell lines. Three factors were obtained by the principal factor analysis method. After the varimax rotation of these three factors, tumor cell lines were classified into four groups according to their factor loadings. The platinum complexes were characterized by the factor scores. Cisplatin was situated in an extreme position as compared with the other platinum complexes. In vivo antitumor activities of the platinum complexes were tested against L1210 and LL murine tumor models. The in vivo activity against L1210 showed a negative correlation with that against LL. Factor 2 scores of the complexes obtained by factor analysis of in vitro antitumor activities showed a good correlation with these in vivo antitumor activities. Then, the structure-factor 2 score relationships among platinum complexes were analyzed by the Free-Wilson method. From this analysis, structure-activity relationships for carrier ligands and leaving groups are proposed. Factor analysis is suggested to be a useful method to establish an efficient screening system for platinum complexes.
Catalysis by a platinumtin complex, [(CH3),N]3[Pt(SnC13),1, in acetone solution has been studied for the hydrogenation of ethylene within the temperature range 0 to 15°C and at low pressures up to 100 Torr. An induction period on hydrogenation was scarcely observed and good reproducibility was shown in a repeated use of the complex as catalyst. Solvent acetone was not hydrogenated under the conditions of reaction. The dependence of the initial rate of ethane formation on catalyst concentration exhibited two maxima in the range 1.0 x to 5.0 x mol dm-3. Kinetic and spectroscopic studies revealed that cluster complexes of various size are dispersed in the solution and showed, with the help of distribution statistics, that the complexes containing one and six Pt-atoms are responsible for the respective rate maxima.* uncertainties are within 5%.
SUMMARYA promising antitumor drug, cis-1,l-cyclobutane-dicarboxylato (2R)-2-methyl-1,4-butanediamine platinum(II), NK121, was synthesized from radionuclides of platinum such as 193mPt, l9SmPt and 191Pt which were produced by neutron irradiation of enriched lg2Pt. The overall yield was 38.6% in a synthesis time of 10 hours. The radioactivities present in 8.39 mg of NK121 were 115.3 pCi as 193mPt, 29.9 pCi as l97Pt, 22.0 pCi as 195mPt, and 4.8 pCi as lglPt at the end of synthesis. The specific activity of the NK121 was 13.7 pCi (193mPt)/mg NK121 at the end of synthesis. The radiochemical purity of NK121 was typically 99 %. HPLC analyses confirmed that NK121 was in an adequate chemical purity and suitable for animal experimentation.
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