Syntheses of New Anti-tumor Platinum Complexes in the Light of Di-region Theory

Di-region theory discovers that the key step of chemical carcinogenesis is the cross-linking between the complementary base pair of DNA double helix, in order to raise the selectivity and strength the activity of anti-tumor agent, so that the design of new anti-tumor agent should reduce the ability of the above-mentioned cross-linking, but should strengthen the cross-linking capability between the non-complementary base pair or within the one strand only. It can be anticipated in terms of the Di-region theory, that the various benzylamino congeners of the important drug cisplatin would satisfy the above requirement due to the interaction between the two phenyl groups and histone, as well as the formation of epoxide from the metabolism of benzene rings in cancer cell. Over dozen of (RC₆H₄ CHYNH₂) PtX₂ type complexes have been synthesized in this laboratory, where R=o-,m-or p- Cl, Br,CH₃O- and CH₃-;Y=H or CH₃-;X=Cl or I.Their tumor cell killing ratio including of iodo congeners for B 16, Hela and human gastric carcinoma cell, the majority are double of the corresponding cisplatin control. This encouraging results were seldom seen in the previous platinum complex syntheses, and the animal tests as well as the syntheses of other congeners based upon Di-region theory, are now being undertaken in the laboratory.