Anticancer agents, complexes

In 1985, it was reported by Hsiang et al. [43] that the cytotoxic activity of 20-(S)-camptothecin (CPT III) was attributed to a novel mechanism of action involving the nuclear enzyme topo I, and this discovery of unique mechanism of action revived the interest in CPT and its analogues as anticancer agents. CPT stabilizes the covalent, reversible topo I-DNA complex leading to the inhibition of DNA synthesis in mammalian cells and interferes with the topo I breakage-reunion reaction [44]. Clinical trials and structure-activity relationships have demonstrated the requirement of the a-hydroxy group, the... 

Farrell, N. In Polynuclear Charged Platinum Complexes as a New Class of Anticancer Agents Kelland, L. R., Farrell, N., Eds. Humana Press Totowa, NJ,... 

The affinity of platinum(II) for N-donor ligands is well established. There are numerous examples in the literature of mono-, di-, and trinuclear platinum(II)-ammine and alkylamine complexes, most of which are structural analogues of the anticancer agent, mplatin (cis- PtCl2(NH3)2]), and the corresponding trans isomer. Selected novel complexes and synthetic methods are presented below. 

The interaction of platinum(II) complexes with various amino acids and simple peptides is relevant to understanding the biological fate of platinum anticancer agents such as mplatin, and this area has been reviewed extensively.258-261... 

PLATINUM COMPLEXES AS THERAPEUTIC AGENTS 9.18.2.1 Clinically Used Anticancer Agents. CA-platinum Compounds... 

The iodido-Pt(IV) complexes thus provided a proof-of-principle being photoactive, but the complexes still suffered from slow photoreactions and, importantly, limited stability in the dark especially against biological reducing agents such as glutathione, which results in undesired toxicity of the anticancer agents in the dark. 

Mixed-ligand Cu(II) complexes with salicylato and phenanthroline derivatives as ligands can also be highly cytotoxic (231). Mixed-ligand Cu(II) amino acid phenanthroline complexes (Casiopeinas) such as [Cu(L-Ser)(phen)(H20)]+ 52 are reported to be effective anticancer agents (232). It is possible that a complex in this class will soon enter clinical trials. 

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