The Critical Distance for the Cycloaromatization Reactions of Enediynes

Author(s): Joseph F. Capitani, Shannon M. Gaffney, Lyana Castaldo, Abhijit Mitra

Journal Name: Current Topics in Medicinal Chemistry

Volume 8 , Issue 6 , 2008

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It has been shown that the enediyne anticancer antibiotics e.g., calicheamicin, neocarzinostatin and others cleave DNA via the putative intermediate 1,4-diradical formed in the Bergmann cyclization and are thus useful for cancer chemotherapy. The pharmacological activity of these drugs is based, in general, on the activation of the pharmacophore and the subsequent cyclization leading to the formation of a radical, the rate of which is, in part, based on the terminal distance of the 1,5-diyne functionality, also known as the critical distance. But the critical distance alone cannot govern the rate of cyclization of the enediynes. A theoretical model has been developed to predict the rate of cyclization, and the thus the pharmacological activity, of these antibiotics based on the critical distance and the energy of activation.

Keywords: Enediynes, cycloaromatization, Hopf cyclization, Myers-Saito cyclization, Bergman cyclization, critical distance model, antitumor antibiotics, QSAR

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Article Details

Year: 2008
Page: [470 - 486]
Pages: 17
DOI: 10.2174/156802608783955719
Price: $65

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