Camptothecin: current perspectives

被引：368

作者：

Thomas, CJ

Rahier, NJ

Hecht, SM

机构：

[1] Univ Virginia, Dept Chem, Charlottesville, VA 22901 USA

[2] Univ Virginia, Dept Biol, Charlottesville, VA 22901 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY | 2004年 / 12卷 / 07期

关键词：

D O I：

10.1016/j.bmc.2003.11.036

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 1, 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. (C) 2004 Elsevier Ltd. All rights reserved.

引用

收藏

页码：1585 / 1604

页数：20

相关论文

共 181 条

[1] CHARACTERIZATION OF A MAMMALIAN MUTANT WITH A CAMPTOTHECIN-RESISTANT DNA TOPOISOMERASE-I [J].

ANDOH, T ;

ISHII, K ;

SUZUKI, Y ;

IKEGAMI, Y ;

KUSUNOKI, Y ;

TAKEMOTO, Y ;

OKADA, K .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1987, 84 (16) :5565-5569

[2] Design and optimization of camptothecin conjugates of triple helix-forming oligonucleotides for sequence-specific DNA cleavage by topoisomerase [J].

Arimondo, PB ;

Boutorine, A ;

Baldeyrou, B ;

Bailly, C ;

Kuwahara, M ;

Hecht, SM ;

Sun, JS ;

Garestier, T ;

Hélène, C .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2002, 277 (05) :3132-3140

[3] Homocamptothecin, an E-ring-modified camptothecin analogue, generates new topoisomerase I-mediated DNA breaks [J].

Bailly, C ;

Lansiaux, A ;

Dassonneville, L ;

Demarquay, D ;

Coulomb, H ;

Huchet, M ;

Lavergne, O ;

Bigg, DCH .

BIOCHEMISTRY, 1999, 38 (47) :15556-15563

[4] Homocamptothecins: potent topoisomerase I inhibitors and promising anticancer drugs [J].

Bailly, C .

CRITICAL REVIEWS IN ONCOLOGY HEMATOLOGY, 2003, 45 (01) :91-108

[5] DNA BREAKAGE AND CLOSURE BY RAT-LIVER TYPE-1 TOPOISOMERASE - SEPARATION OF THE HALF-REACTIONS BY USING A SINGLE-STRANDED-DNA SUBSTRATE [J].

BEEN, MD ;

CHAMPOUX, JJ .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-BIOLOGICAL SCIENCES, 1981, 78 (05) :2883-2887

[6] Addition of ester enolates to N-alkyl-2-fluoropyridinium salts:: Total synthesis of (±)-20-deoxycamptothecin and (+)-camptothecin [J].

Bennasar, ML ;

Zulaica, E ;

Juan, C ;

Alonso, Y ;

Bosch, J .

JOURNAL OF ORGANIC CHEMISTRY, 2002, 67 (21) :7465-7474

[7]

BENNASAR ML, 2000, J CHEM SOC CHEM COMM, V24, P2459

[8] Total synthesis of (+)-camptothecin [J].

Blagg, BSJ ;

Boger, DL .

TETRAHEDRON, 2002, 58 (32) :6343-6349

[9] REACTIONS WITH INDOLE-DERIVATIVES .17. BIOGENETICALLY ORIENTATED TOTAL-SYNTHESIS OF DL-CAMPTOTHECIN AND 7-CHLOROCAMPTOTHECIN [J].

BOCH, M ;

WINTERFELDT, E ;

NELKE, JM ;

RADUNZ, H ;

PIKE, D ;

KORTH, T .

CHEMISCHE BERICHTE-RECUEIL, 1972, 105 (07) :2126-+

[10] Novel A,B,E-ring-modified camptothecins displaying high lipophilicity and markedly improved human blood stabilities [J].

Bom, D ;

Curran, DP ;

Chavan, AJ ;

Kruszewski, S ;

Zimmer, SG ;

Fraley, KA ;

Burke, TG .

JOURNAL OF MEDICINAL CHEMISTRY, 1999, 42 (16) :3018-3022

← 1 2 3 4 5 6 7 8 9 10 →