Cisplatin anticancer agent

Pt Polynuclear PtIV species Anticancer agents BBR3464, Satraplatin, AMD-473 Expands spectmm of activity of cisplatin overcomes resistance oral activity ... 

Figure 4 Hydrolysis scheme for cisplatin-based anticancer agents. Where L = U = NH3 cisplatin is indicated. When L = NH3 and V = 2-picoline or cha the rates of aquation of the trans-chloride ligands are different.

Pt Cisplatin, platinol, cisDDP cis-[Pt(NH3)2Cl2] Anticancer agent... 

Sedletska Y, Giraud-Panis MJ, Malinge JM (2005) Cisplatin is a DNA-damaging antitumour compound triggering multifactorial biochemical responses in cancer cells importance of apoptotic pathways. Curr Med Chem Anticancer Agents 5(3) 251-265... 

Cisplatin, an anticancer agent used for the treatment of solid tumors, is prepared by the reaction of ammonia with potassium tetrachloroplatinate ... 

Experiments in this laboratory identified apoptosis as a consequence of the action of cisplatin and many other anticancer agents [50-52], Many authors have subsequently misquoted these results when suggesting that cisplatin kills by apoptosis, and that suppression of apoptosis is a mechanism of resistance. It should be evident by now that apoptosis is better defined as a consequence of the mechanism of action of cisplatin and a failure of the mechanisms of resistance. Apoptosis is certainly not an alternative to the formation of DNA cross-links, nor to the cell-cycle perturbations that result these are still essential events in the initiation phase of apoptosis. The mechanisms of resistance to cisplatin still include reduced drug accumulation, reduced DNA platination, and altered DNA repair. However, apoptosis provides a framework for understanding the complete pathway from initial insult to eventual death of a cell. It provides the realization that there are additional factors that influence cell survival and death. Expression of Bcl-2 family members or changes in signal transduction pathways impact... 

In order to understand all aspects of the action of cisplatin as an anticancer agent, further structural research on the complexes between HMG-domain proteins and platinated DNA fragments will be necessary. On the other hand, further studies of small model compounds may furnish several new details of the chemistry controlling cisplatin-DNA interactions. 

Fig. 3 Venn-diagram for selected compounds interacting with the key MDR-related ABC transporters. MDR-substrate anticancer agents. Abbreviations VCR vincristine, VP-16 etoposide, STER steroids, TAM tamoxiphen, TKI-INHIB tyrosin kinase inhibitors e.g. STI-571, DOX doxorubicine or adriamycin, DNR daunorubicin, EPIR epirubicin, MX mitoxantrone, TOPOT topotecan, iridotecan, BISANT bisanthrone, COLCH colchicin, ACT-D actinomycin D, MYTOM mytomycin, TX methotrexate, CPHAM cyclophosphamide, CHLB chlorambucil, CARM carmustine, LCV leucovorin, HUR hydroxy urea, CISPL cisplatin, TAXOL paclitaxel. (Reproduced from [4])...

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