Improved understanding in platinium antitumour chemistry

Abstract

After the serendipitous rediscovery of cisplatin{cis-[PtCl₂(NH₃)₂], first synthesized in 1845} in 1964 by Rosenberg, and its routine use as a successful cytostatic durg since 1979, exciting chemistry has resulted from several laboratories, using this simple compound and a variety of its derivatives. The major chemical features that have led to a significant improvement of our insight into the mechanism of action are discussed in this feature acticle. Key elements appear to be: (i) controlled hydrolysis, transport and binding to DNA; (ii) a specific binding at neighbouring guanine bases; and in particular (iii) a specific distortion of DNA, changing its interactions with proteins.