Cisplatin: Chemistry and Biochemistry of a Leading Anticancer Drug

Abstract

Part I The start: platinum complexes for the treatment of cancer - why the search goes on. Part II Cisplatin - how good is it?: clinical status of cisplatin and other PT antitumor drugs. Part III How does it possibly work? - biochemistry: the response of cellular proteins to cisplatin - damaged DNA the mechanism of action of cisplatin - from adducts to apoptosis replication of platinated DNA and its mutagenic consequences interstand cross-links in cisplatin- or transplatin-modified DNA. Part IV Chemistry relevant to PT-biomolecule interactions: platinum complexes - hydrolysis and binding to N7 and N1 of purines reactivity and inertness of PT-nucleobase complexes kinetics and selectivity of DNA platination structure and dynamics of PT anticancer drug adducts from nucleotides to oligonucleotides as revealed by NMR methods 195Pt and 15N NMR spectroscopic studies of cisplatin reactions with biomolecules structural aspects of PT-purine interactions - from models to DNA platinum-sulfur interactions involved in antitumor drugs, rescue agents and biomolecules diammine- and diamineplatinum complexes with non-sulfur-containing amino acids and peptides. Part V Inorganic chemistry revived or initiated by cisplatin: platinum blues - on the way toward unraveling a mystery heteronuclear PT(II) complexes with pyrimidine nucleobases displatinum(III) complexes - chemical species more widely spread than suspected inorganic and organometallic chemistry of cisplatin-derived PT(III) complexes. Part VI New developments: structure-activity relationships within di- and trinuclear platinum phase I clinical anticancer agents the development of orally-active platinum drugs methods for screening the potential antitumor activity of platinum compounds in combinatorial libraries computational studies on platinum antitumor complexes and their adducts with nucleid acids constituents.