Total and semisynthesis and in vitro studies of both enantiomers of 20-fluorocamptothecin

Raghuram S. Tangirala, Rachel Dixon, Danzhou Yang, A. Ambrus, Smitha Antony, Keli Agama, Yves Pommier, Dennis P. Curran

Research output: Contribution to journalArticle

15 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)4736-4740
Number of pages5
JournalBioorganic and Medicinal Chemistry Letters
Volume15
Issue number21
DOIs
Publication statusPublished - Nov 1 2005

Fingerprint

Camptothecin
Enantiomers
Type I DNA Topoisomerase
Lactones
Assays
20-fluorocamptothecin
In Vitro Techniques

Keywords

  • Camptothecin
  • Isonitrile radical annulation
  • Topoisomerase I

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

Cite this

Total and semisynthesis and in vitro studies of both enantiomers of 20-fluorocamptothecin. / Tangirala, Raghuram S.; Dixon, Rachel; Yang, Danzhou; Ambrus, A.; Antony, Smitha; Agama, Keli; Pommier, Yves; Curran, Dennis P.

In: Bioorganic and Medicinal Chemistry Letters, Vol. 15, No. 21, 01.11.2005, p. 4736-4740.

Research output: Contribution to journalArticle

Tangirala, RS, Dixon, R, Yang, D, Ambrus, A, Antony, S, Agama, K, Pommier, Y & Curran, DP 2005, 'Total and semisynthesis and in vitro studies of both enantiomers of 20-fluorocamptothecin', Bioorganic and Medicinal Chemistry Letters, vol. 15, no. 21, pp. 4736-4740. https://doi.org/10.1016/j.bmcl.2005.07.074
Tangirala, Raghuram S. ; Dixon, Rachel ; Yang, Danzhou ; Ambrus, A. ; Antony, Smitha ; Agama, Keli ; Pommier, Yves ; Curran, Dennis P. / Total and semisynthesis and in vitro studies of both enantiomers of 20-fluorocamptothecin. In: Bioorganic and Medicinal Chemistry Letters. 2005 ; Vol. 15, No. 21. pp. 4736-4740.
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