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Chemical and Biological Explorations of the Family of CC-1065 and the Duocarmycin Natural Products.
Ghosh, Nandita Sheldrake, Helen M. Searcey, M. Pors, Klaus
Ghosh, Nandita
Sheldrake, Helen M.
Searcey, M.
Pors, Klaus
Publication Date
2009-10
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© 2009. Bentham Science Publishers. Reproduced in accordance with the publisher's self-archiving policy.
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Abstract
CC-1065, the duocarmycins and yatakemycin are members of a family of ultrapotent antitumour antibiotics that
have been the subject of extensive investigations due to their mode of action and potential in the design of new anticancer
therapeutics. The natural products and their analogues exert their effects through a sequence selective alkylation of duplex
DNA in the minor groove at the N3 of adenine. An understanding of their structure and its effect on biological activity has
been derived through chemical synthesis and has also generated new potential lead compounds. These studies form the
first section of the review. The desire to progress these compounds to clinic has also led to studies of bioconjugation and
prodrug formation and this is discussed in the second section of the review. The combination of synthesis with key
biological experiments is a powerful tool to define the requirements for the development of natural products as potential
therapeutic agents. The studies described herein form an excellent paradigm for the study and development of other
natural products.
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Citation
Ghosh N, Sheldrake HM, Searcey M et al (2009) Chemical and biological explorations of the family of CC-1065 and the duocarmycin natural products. Current Topics in Medicinal Chemistry. 9(16): 1494-1524.
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