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Current Topics in Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 1568-0266
ISSN (Online): 1873-4294

The Critical Distance for the Cycloaromatization Reactions of Enediynes

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

Volume 8, Issue 6, 2008

Page: [470 - 486] Pages: 17

DOI: 10.2174/156802608783955719

Price: $65

Abstract

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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