Bleomycin antitumor natural product

Hecht SM. Bleomycin group antitumor agents. In Anticancer Agents from Natural Products. Cragg GM, Kingston DGI, Newman DJ, eds. 2005. Taylor and Francis, Boca Raton, FL. pp. 357-381. 

Many important therapeutics, in use in clinics today, are biosynthesized by the nonribosomal peptide synthetase (NRPS) and polyketide synthase (PKS) paradigm. For example, many of the antibiotics (penicillin, cephalosporin, vancomycin, erythromycin, etc.), immunosuppressors (cyclosporine, rapamycin), antiviral agents (luzopeptin A), antitumor agents (bleomycin), and toxins (thaxtomin) are NRPS and PKS derived.20-22 Figure 1 displays a small selection of natural products that are NRPS and PKS derived and illustrates the diversity of molecular structures generated by these biosynthetic paradigms. 

There are now more than forty drugs approved for the treatment of human cancer in the United States. Considering the thousands of compounds that have been tested as candidate antitumor agents, this is a highly select group. Among them are two drugs that require a metal ion as part of their structures. One is the simple metal complex cis-diamminedichloroplatinum(ii). The other, bleomycin, is a natural product that must form an iron complex to display cytotoxicity. In addition, two anthracycline natural products, doxorubicin or adriamycin, and daunomycin, may also function as iron complexes or utilize cellular iron in an indirect way in their mechanisms of action. 

The second class of natural products we shall discuss are NRPs. Similar to the PK natural products, NRPs have found widespread clinical use. Representative members of this class of natural products include the antibiotics vancomycin (4, Figure 4.1), penicillin, bacitracin, and actinomycin D the antitumor drug bleomycin the immunosuppressant cyclosporine A and the siderophore enterobactin." ... 

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