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TitleTotal and semisynthesis and in vitro studies of both enantiomers of 20-fluorocamptothecin
Publication TypeJournal Article
Year of Publication2005
AuthorsTangirala, R.S., Dixon R., Yang D., Ambrus A., Antony S., Agama K., Pommier Y., and Curran D.P.
JournalBioorganic and Medicinal Chemistry Letters
Pagination4736 - 4740
Date Published2005
ISSN0960894X (ISSN)
Keywords20 fluorocamptothecin, Antineoplastic Agents, article, Camptothecin, camptothecin derivative, DNA, DNA determination, DNA topoisomerase, DNA Topoisomerases, Type I, drug activity, drug DNA binding, drug protein binding, drug synthesis, enantiomer, Enzyme Inhibitors, Humans, Hydrogen bonding, Hydrolysis, hydroxyl group, in vitro study, Kinetics, lactone, phosphate buffered saline, racemic mixture, Stereoisomerism, Structure-Activity Relationship, unclassified drug
AbstractBoth enantiomers of 20-fluorocamptothecin and the racemate have been prepared by total synthesis. The (R)-enantiomer is essentially inactive in a topoisomerase-I/DNA assay, while the (S)-enantiomer is much less active than (20S)-camptothecin. The lactone ring of 20-fluorocamptothecin hydrolyzes more rapidly than that of camptothecin in PBS. The results provide insight into the role of the 20-hydroxy group in the binding of camptothecin to topoisomerase-I and DNA. © 2005 Elsevier Ltd. All rights reserved.

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