Camptothecin: Current perspectives

Craig J. Thomas; Nicolas J. Rahier; Sidney M. Hecht

doi:10.1016/j.bmc.2003.11.036

Camptothecin: Current perspectives

Craig J. Thomas, Nicolas J. Rahier, Sidney M. Hecht

Research output: Contribution to journal › Review article › peer-review

359 Scopus citations

Abstract

This review provides a detailed discussion of recent advances in the medicinal chemistry of camptothecin, a potent antitumor antibiotic. Two camptothecin analogues are presently approved for use in the clinic as antitumor agents and several others are in clinical trials. Camptothecin possesses a novel mechanism of action involving the inhibition of DNA relaxation by DNA topoisomerase I, and more specifically the stabilization of a covalent binary complex formed between topoisomerase I and DNA. This review summarizes the current status of studies of the mechanism of action of camptothecin, including topoisomerase I inhibition and additional cellular responses. Modern synthetic approaches to camptothecin and several of the semi-synthetic methods are also discussed. Finally, a systematic evaluation of novel and important analogues of camptothecin and their contribution to the current structure-activity profile are considered.

Original language	English (US)
Pages (from-to)	1585-1604
Number of pages	20
Journal	Bioorganic and Medicinal Chemistry
Volume	12
Issue number	7
DOIs	https://doi.org/10.1016/j.bmc.2003.11.036
State	Published - Apr 1 2004
Externally published	Yes

ASJC Scopus subject areas

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

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10.1016/j.bmc.2003.11.036

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title = "Camptothecin: Current perspectives",

abstract = "This review provides a detailed discussion of recent advances in the medicinal chemistry of camptothecin, a potent antitumor antibiotic. Two camptothecin analogues are presently approved for use in the clinic as antitumor agents and several others are in clinical trials. Camptothecin possesses a novel mechanism of action involving the inhibition of DNA relaxation by DNA topoisomerase I, and more specifically the stabilization of a covalent binary complex formed between topoisomerase I and DNA. This review summarizes the current status of studies of the mechanism of action of camptothecin, including topoisomerase I inhibition and additional cellular responses. Modern synthetic approaches to camptothecin and several of the semi-synthetic methods are also discussed. Finally, a systematic evaluation of novel and important analogues of camptothecin and their contribution to the current structure-activity profile are considered.",

author = "Thomas, {Craig J.} and Rahier, {Nicolas J.} and Hecht, {Sidney M.}",

note = "Funding Information: This review is dedicated to the memory of Dr. Monroe Wall. We thank Dr. Christopher Claeboe and David Maloney for helpful discussions during the writing of this review. Work in our laboratory has been supported by NIH research grant CA78415, awarded by the National Cancer Institute, and by American Cancer Society fellowship PF-02-090-01-CDD (to C. J. T.). ",

year = "2004",

month = apr,

day = "1",

doi = "10.1016/j.bmc.2003.11.036",

language = "English (US)",

volume = "12",

pages = "1585--1604",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Limited",

number = "7",

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TY - JOUR

T1 - Camptothecin

T2 - Current perspectives

AU - Thomas, Craig J.

AU - Rahier, Nicolas J.

AU - Hecht, Sidney M.

N1 - Funding Information: This review is dedicated to the memory of Dr. Monroe Wall. We thank Dr. Christopher Claeboe and David Maloney for helpful discussions during the writing of this review. Work in our laboratory has been supported by NIH research grant CA78415, awarded by the National Cancer Institute, and by American Cancer Society fellowship PF-02-090-01-CDD (to C. J. T.).

PY - 2004/4/1

Y1 - 2004/4/1

N2 - This review provides a detailed discussion of recent advances in the medicinal chemistry of camptothecin, a potent antitumor antibiotic. Two camptothecin analogues are presently approved for use in the clinic as antitumor agents and several others are in clinical trials. Camptothecin possesses a novel mechanism of action involving the inhibition of DNA relaxation by DNA topoisomerase I, and more specifically the stabilization of a covalent binary complex formed between topoisomerase I and DNA. This review summarizes the current status of studies of the mechanism of action of camptothecin, including topoisomerase I inhibition and additional cellular responses. Modern synthetic approaches to camptothecin and several of the semi-synthetic methods are also discussed. Finally, a systematic evaluation of novel and important analogues of camptothecin and their contribution to the current structure-activity profile are considered.

AB - This review provides a detailed discussion of recent advances in the medicinal chemistry of camptothecin, a potent antitumor antibiotic. Two camptothecin analogues are presently approved for use in the clinic as antitumor agents and several others are in clinical trials. Camptothecin possesses a novel mechanism of action involving the inhibition of DNA relaxation by DNA topoisomerase I, and more specifically the stabilization of a covalent binary complex formed between topoisomerase I and DNA. This review summarizes the current status of studies of the mechanism of action of camptothecin, including topoisomerase I inhibition and additional cellular responses. Modern synthetic approaches to camptothecin and several of the semi-synthetic methods are also discussed. Finally, a systematic evaluation of novel and important analogues of camptothecin and their contribution to the current structure-activity profile are considered.

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U2 - 10.1016/j.bmc.2003.11.036

DO - 10.1016/j.bmc.2003.11.036

M3 - Review article

C2 - 15028252

AN - SCOPUS:1542507062

VL - 12

SP - 1585

EP - 1604

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

SN - 0968-0896

IS - 7

ER -

Camptothecin: Current perspectives

Abstract

ASJC Scopus subject areas

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