Anticancer drugs replication

A major point that needs to be addressed in future work is the targeted delivery of organometallic anticancer drugs to cancer cells only. Also, additional features that generate cytotoxic activity other than disruption of DNA replication, such as the inclusion of molecular fragments that can interfere in cancer cell-specific cellular pathways, could be explored (11,103). 

Cisplatin (dx-Diamminedichloroplatinum) is a divalent water-soluble platinum containing complex. It reacts directly with DNA, resulting in both intra-and inter-strand cross-links. It also causes DNA breaks and it inhibits DNA replication and RNA transcription. A mechanism for the occurrence of resistance appears to be an increased of the levels of DNA-excision repair enzymes. Cisplatin is used in combination therapies with other anticancer drugs in the treatment of testicular and ovarian cancers and it has also shown high activity against cancers of the bladder, head, neck and endometrium. It is administered intravenously by rapid injection or by continuous infusion. It is for more that 90% bound to... 

Bu may pair with G, however, as if it were C (Fig. 6.44), with the consequence that G C to A T and A T to G C transitions result. The first type of transition occurs because of erroneous incorporation and the second results from erroneous replication against the incorporated Bu. Other base analogues, some of which are used as anticancer drugs, may produce lethal mutations in mammalian cells, particularly in cancerous cells, which are involved in rapid DNA synthesis. 

The triazole ribofuranoside ribavirin (101) has been used clinically against influenza, parainfluenza and herpes infections with varying results, and imidazole ribofuranosides are active in vitro. The antibiotic pyrazofurin (102) inhibits the replication of many viruses and has also been tried as an anticancer drug. 

The study of various anticancer drugs shows that many possess an optimal circadian delivery pattern, according to the phase of the cell cycle in which the cytotoxic effect is exerted. A case in point is provided by 5-FU. This widely used anticancer drug interferes with DNA synthesis and acts during DNA replication, the S phase of the cell cycle. Cells exposed to 5-FU during the S phase have an enhanced proba-... 

A variety of plant substances with planar, polycyclic, aromatic structures can intercalate with DNA, examples being the quinoline alkaloid camptothecin and the furanocoumarin phenolic psoralen (Table 12.1). A variety of plant-derived anthraquinones and naphthoquinones bind to DNA and it is notable that the structurally related anthraquinones mitox-antrone and adriamycin are clinically employed as anticancer drugs (Table 12.1). DNA-binding compounds that interfere with DNA repair, DNA replication and gene expression are cytotoxic and have potential as anticancer agents (see Chapter 9). 

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