Synthesis and Antitumor Activity of cis-Dichloroplatinum Complexes Coordinating Nitrogen Cyclic or Sulfur Compounds

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cis-Dichloroplatinum complexes of nitrogen cyclic compounds and sulfur-containing compounds were synthesized through the reaction of K_2PtCl_4 with the corresponding ligands in water or an interfacial layer between water and an organic solvent. The effect of substituents of pyridine derivatives on the synthesis of the cis-platinum complexes depended greatly on their position. The coordination of 2-substituted pyridines required a long reaction time and the yields were low. That of 3- or 4-substituted pyridines proceeded smoothly in high yields. The complexes coordinating dimethyl- or trimethyl-substituted pyridines were obtained in low yields, but a methyl group at the para position increased the coordination activity of pyridines. The reactivity of other nitrogen cyclic compounds depended greatly on their structures and no clear correlation between structure and reactivity was observed. In some cases, polynuclear or unidentified complexes were formed. Sulfurcontaining compounds reacted smoothly in high yields.Three synthesized cis-dichloroplatinum(II) complexes coordinating di(3-methylpyridine), di(quinoline) and di(isoquinoline) and a polynuclear platinum piperidine complex (Pt_4Cl_5(OH)_3-(C_5H_<11>N)_6・3H_2O) had high antitumor activities against Sarcoma 180 ascites in female ICR/CRJ mice. The required platinum weight of these effective complexes for antitumor activity was in the range of 23-94 mg/kg in mice compared with 5 mg/kg in the case of cis-dichlorodiammineplatinum.
社団法人日本薬学会の論文
1986-09-25

Synthesis and Antitumor Activity of cis-Dichloroplatinum Complexes Coordinating Nitrogen Cyclic or Sulfur Compounds

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