ABSTRACT
The enediyne antitumor antibiotics represent some of the most potent, biologically active natural products ever discovered. These compounds possess both antibacterial and antitumor activities and are related by containing enediyne functionality constrained within 9-or 10-membered rings, with varying degrees of chemical complexity in the remainder of the molecules. Most of these antitumor antibiotics are produced by microorganisms classiœed as the actinomycetes. The challenging chemical structures of these enediynes, their mechanisms of action, and their biological activity have attracted considerable scientiœc attention. Two of these compounds, neocarzinostatin and esperamicin A1, were advanced into anticancer clinical trials as single agents. Esperamicin A1 was eventually abandoned from further development because of toxicity issues. However, neocarzinostatin has been approved for human use in Japan for a number of cancer indications, both as the natural product itself as well as a part of a polymer-based conjugate. A monoclonal antibody conjugate of calicheamicin was successful in clinical trials and has been commercialized for the treatment of acute myelogenous leukemia in adults.
