基于双区理论的新抗癌铂络合物合成

<正>一切抗癌的烷化剂同时也都是致癌的，铂络合物抗癌药也井不例外‘”。双区理论发现，致癌剂引发细胞癌变的关键步骤是互补碱对间的横向交联。抗癌剂研究的长期实践证朋，癌细胞的修复能力虽然弱于正常哺乳动物细胞，却强于原核细胞，所以抗癌要求双官能或多官能烷化剂，或在体内形成的双官能烷化剂的作用。即对于杀伤癌细胞，引起其股内和股间的各种形式的横向交联是必要的。氮芥等多数抗癌烷化剂，其亲电中心的距离远超过 2.80一3.00人，共引起的股间横向交联必然主要是非互补碱对性质的，因此抗癌并不一定要求互补碱对之间的横向交联。因此，为了加强抗癌烷化剂对正常细胞和癌细胞作用的选择性，双区理论在抗癌剂合成中的必然可以引伸的指导思想，是应力图促使抗癌药在体内引起DNA股内或股间非互补碱对的交联，而避免互补碱对的交联。

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.