Total and semisynthesis and in vitro studies of both enantiomers of 20-fluorocamptothecin.
Both 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.
Tangirala
Raghuram S
RS
Department of Chemistry, University of Pittsburgh, Pittsburgh, PA 15260, USA.
Dixon
Rachel
R
Yang
Danzhou
D
Ambrus
Attila
A
Antony
Smitha
S
Agama
Keli
K
Pommier
Yves
Y
Curran
Dennis P
DP
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002166:Camptothecin / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D006860:Hydrogen Bonding; D006868:Hydrolysis; D007700:Kinetics; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors
C506412:20-fluorocamptothecin; D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D059004:Topoisomerase I Inhibitors; D002166:Camptothecin