[Development of antitumor platinum complexes].
Since the discovery of the antitumor activity of cis-dichlorodiammine platinum (II) in various tumor systems by B. Rosenberg in 1969, many Pt complexes have been prepared to ameliolate DDP. It has been known to have severe nephrotoxicity, nausea and vomiting, as well as ototoxicity. However, DDP has a wide spectrum of antitumor activity, and it is specifically active against cancers in bladder, testis, ovary and, head and neck. To attenuate such toxicities, hydration prior to DDP administration and/or application of diuretics, as well as combination therapy with other antitumor agents have been developed. Various studies indicated that the nephrotoxicity was attenuated by changing carrier ligands and leaving groups. Toxicity to be removed so far is myelosuppression and vomiting. Another problem is the cross-resistance of DDP. Against L1210/DDP, amine, ethylenediamine, o-phenylenediamine and 1,2-cyclopentanediamine Pt complexes showed cross-resistance, while dach and 1,2-cycloheptanediamine Pt complexes showed no cross-resistance. In this review, the author discusses mainly preparation of the Pt complex of the 2nd generation, being now in the clinical trials and my approach to the development of the antitumor Pt complexes in my laboratory. Pt complexes being now in the advanced studies are: CBDCA, CHIP, DACCP, PYPl PHIC, TNO-6 and l-OHP. New Pt complexes are still deviced continuously. The capability of synthesizing Pt complexes which are characteristically effective against the slow-growing solid tumors, from the standpoint of the coordination chemist.
D000818:Animals; D000970:Antineoplastic Agents; D016190:Carboplatin; D002945:Cisplatin / Q000494:pharmacology / Q000633:toxicity; D003514:Cyclohexylamines / Q000494:pharmacology; D006801:Humans; D007668:Kidney / Q000187:drug effects; D009369:Neoplasms / Q000188:drug therapy; D009374:Neoplasms, Experimental / Q000188:drug therapy; D009944:Organoplatinum Compounds / Q000494:pharmacology; D010984:Platinum / Q000494:pharmacology / Q000633:toxicity; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D003514:Cyclohexylamines; D009944:Organoplatinum Compounds; D010984:Platinum; C023359:iproplatin; D016190:Carboplatin; C030435:1,2-cyclohexanediamine; C040757:spiroplatin; D002945:Cisplatin