Natural and Designed Enediyne Antibiotics

Enediynes hold substantial promise as anticancer drugs because of their potency and selectivity. Not only do they inhibit cell growth, they have a greater tendency to kill cancer cells than they do normal cells. The mechanism by which enediynes act involves novel chemistry unique to the C=C—C=C—C=C unit, which leads to a species that cleaves DNA and halts tumor growth. 

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In spite of the fact that few cycloalkynes occur naturally, they gained recent attention when it was discovered that some of them hold promise as anticancer drugs. (See the boxed essay Natural and Designed Enediyne Antibiotics following this section.)... 

However, as there is no free DNA in the cell, and the real target for DNA-inter-active agents is the chromatin, it is not clear whether in vitro studies can contribute to understanding of cellular DNA sequence selectivity. Various synthetic approaches and mechanistic studies assisted by computer aided molecular design (CAMD) have been described aiming at an optimization of the pharmacological properties of the enediyne antibiotics [80]. It remains to be seen whether enediynes, either natural or designed, will become a useful supplement to the arsenal for the treatment of cancer. 

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