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

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

doi:10.1016/j.bmcl.2005.07.074

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

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

Pharmacology and Toxicology

Research output: Contribution to journal › Article › peer-review

20 Scopus citations

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 language	English (US)
Pages (from-to)	4736-4740
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	15
Issue number	21
DOIs	https://doi.org/10.1016/j.bmcl.2005.07.074
State	Published - Nov 1 2005

Keywords

Camptothecin
Isonitrile radical annulation
Topoisomerase I

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2005.07.074

Cite this

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title = "Total and semisynthesis and in vitro studies of both enantiomers of 20-fluorocamptothecin",

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.",

keywords = "Camptothecin, Isonitrile radical annulation, Topoisomerase I",

author = "Tangirala, \{Raghuram S.\} and Rachel Dixon and Danzhou Yang and Attila Ambrus and Smitha Antony and Keli Agama and Yves Pommier and Curran, \{Dennis P.\}",

note = "Funding Information: We thank the NIH for partial funding of this work. ",

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doi = "10.1016/j.bmcl.2005.07.074",

language = "English (US)",

volume = "15",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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TY - JOUR

T1 - Total and semisynthesis and in vitro studies of both enantiomers of 20-fluorocamptothecin

AU - Tangirala, Raghuram S.

AU - Dixon, Rachel

AU - Yang, Danzhou

AU - Ambrus, Attila

AU - Antony, Smitha

AU - Agama, Keli

AU - Pommier, Yves

AU - Curran, Dennis P.

N1 - Funding Information: We thank the NIH for partial funding of this work.

PY - 2005/11/1

Y1 - 2005/11/1

N2 - 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.

AB - 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.

KW - Camptothecin

KW - Isonitrile radical annulation

KW - Topoisomerase I

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U2 - 10.1016/j.bmcl.2005.07.074

DO - 10.1016/j.bmcl.2005.07.074

M3 - Article

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AN - SCOPUS:25144481437

SN - 0960-894X

VL - 15

SP - 4736

EP - 4740

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 21

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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