Since the discovery of antitumor activity of cis-Platin by Rosenberg in 1969, various Pt complexes were prepared in order to ameliolate severe kidney toxicity, and vomiting and nausea. Pt complexes have usually high antitumor activity against leukemia L1210. Various antitumor Pt complexes were prepared, with an aim to synthesize the 2nd generation Pt complexes with high and specific antitumor activity without or least toxicity. Various Pt complexes of 1, 2-cyclohexanediamine (dach) and 2-(aminomethyl)-cyclohexylamine (amcha) isomers were prepared as carrier ligands, and mono- and bi-dentate leaving groups. Among the carrier ligands, trans-l-dach, and cis-dl- and trans-dl-amcha are found to be the most antitumor active ligands with 5-membered and 6-membered chelate rings. Water-soluble Pt complexes and lipo-soluble Pt complexes were also prepared by the modification of leaving groups. They are highly antitumor active. Among the Pt complexes prepared so far, Pt (oxalato) (trans-l-dach), as well as Pt (D-glucuronato) (trans-l-dach) nitrate and Pt (D-glucuronato)
2 (trans-l-dach) are under development as a new type of the antitumor agent. The interactions of Pt complexes with deoxyribonucleic acid (DNA) were discussed. The mode of action of Pt complexes has been found to be mainly intrastrand crosslinking at N
7 of guanine base. The measurements were carried out by the exonuclease enzyme digestion of Pt-DNA complexes, followed by the detection with high performance liquid chromatography. Pt (oxalato) (trans-l-dach) is recommended as the promising 2nd generation Pt complex.
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