14-Azacamptothecin: A potent water-soluble topoisomerase I poison

Kejun Cheng; Nicolas J. Rahier; Brian M. Eisenhauer; Rong Gao; S. J. Thomas; Sidney M. Hecht

doi:10.1021/ja0442769

14-Azacamptothecin: A potent water-soluble topoisomerase I poison

Kejun Cheng, Nicolas J. Rahier, Brian M. Eisenhauer, Rong Gao, S. J. Thomas, Sidney M. Hecht

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

106 Scopus citations

Abstract

On the basis of an analysis of luotonin A and its D-ring deaza analogue as topoisomerase I poisons and topoisomerase I-dependent cytotoxic agents, a novel analogue of the structurally related antitumor antibiotic camptothecin (CPT) was prepared. 14-Azacamptothecin was found to have much greater aqueous solubility than CPT, to inhibit topoisomerase I-mediated DNA relaxation more efficiently than CPT, and to stabilize the covalent binary complex to almost the same extent. 14-Aza CPT was found to be slightly less active than CPT in mediating cytotoxicity toward yeast expressing human topoisomerase I, possibly as a consequence of its greater off-rate from the CPT-topoisomerase I-DNA ternary complex.

Original language	English (US)
Pages (from-to)	838-839
Number of pages	2
Journal	Journal of the American Chemical Society
Volume	127
Issue number	3
DOIs	https://doi.org/10.1021/ja0442769
State	Published - Jan 26 2005
Externally published	Yes

ASJC Scopus subject areas

Catalysis
General Chemistry
Biochemistry
Colloid and Surface Chemistry

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abstract = "On the basis of an analysis of luotonin A and its D-ring deaza analogue as topoisomerase I poisons and topoisomerase I-dependent cytotoxic agents, a novel analogue of the structurally related antitumor antibiotic camptothecin (CPT) was prepared. 14-Azacamptothecin was found to have much greater aqueous solubility than CPT, to inhibit topoisomerase I-mediated DNA relaxation more efficiently than CPT, and to stabilize the covalent binary complex to almost the same extent. 14-Aza CPT was found to be slightly less active than CPT in mediating cytotoxicity toward yeast expressing human topoisomerase I, possibly as a consequence of its greater off-rate from the CPT-topoisomerase I-DNA ternary complex.",

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T1 - 14-Azacamptothecin

T2 - A potent water-soluble topoisomerase I poison

AU - Cheng, Kejun

AU - Rahier, Nicolas J.

AU - Eisenhauer, Brian M.

AU - Gao, Rong

AU - Thomas, S. J.

AU - Hecht, Sidney M.

PY - 2005/1/26

Y1 - 2005/1/26

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AB - On the basis of an analysis of luotonin A and its D-ring deaza analogue as topoisomerase I poisons and topoisomerase I-dependent cytotoxic agents, a novel analogue of the structurally related antitumor antibiotic camptothecin (CPT) was prepared. 14-Azacamptothecin was found to have much greater aqueous solubility than CPT, to inhibit topoisomerase I-mediated DNA relaxation more efficiently than CPT, and to stabilize the covalent binary complex to almost the same extent. 14-Aza CPT was found to be slightly less active than CPT in mediating cytotoxicity toward yeast expressing human topoisomerase I, possibly as a consequence of its greater off-rate from the CPT-topoisomerase I-DNA ternary complex.

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14-Azacamptothecin: A potent water-soluble topoisomerase I poison

Abstract

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