Dihydroindenoisoquinolines function as prodrugs of indenoisoquinolines

Xiangshu Xiao; Ze Hong Miao; Smitha Antony; Yves Pommier; Mark Cushman

doi:10.1016/j.bmcl.2005.03.101

Dihydroindenoisoquinolines function as prodrugs of indenoisoquinolines

Xiangshu Xiao, Ze Hong Miao, Smitha Antony, Yves Pommier, Mark Cushman

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

28 Scopus citations

Abstract

Dihydroindenoisoquinolines are analogs of cytotoxic indenoisoquinoline topoisomerase I (Top1) inhibitors, exhibiting potent cytotoxicity but weak inhibitory activity toward Top1. Through COMPARE analysis, cytotoxicity studies in Top1-deficient cells, chemical synthesis and biological evaluation of methylated dihydroindenoisoquinoline 5, we demonstrated that dihydroindenoisoquinolines function as prodrugs of indenoisoquinolines in cancer cells.

Original language	English (US)
Pages (from-to)	2795-2798
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	15
Issue number	11
DOIs	https://doi.org/10.1016/j.bmcl.2005.03.101
State	Published - Jun 2 2005
Externally published	Yes

Keywords

Antitumor
Dihydroindenoisoquinoline
Indenoisoquinoline
Prodrug
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.2005.03.101

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title = "Dihydroindenoisoquinolines function as prodrugs of indenoisoquinolines",

abstract = "Dihydroindenoisoquinolines are analogs of cytotoxic indenoisoquinoline topoisomerase I (Top1) inhibitors, exhibiting potent cytotoxicity but weak inhibitory activity toward Top1. Through COMPARE analysis, cytotoxicity studies in Top1-deficient cells, chemical synthesis and biological evaluation of methylated dihydroindenoisoquinoline 5, we demonstrated that dihydroindenoisoquinolines function as prodrugs of indenoisoquinolines in cancer cells.",

keywords = "Antitumor, Dihydroindenoisoquinoline, Indenoisoquinoline, Prodrug, Topoisomerase I",

author = "Xiangshu Xiao and Miao, {Ze Hong} and Smitha Antony and Yves Pommier and Mark Cushman",

note = "Funding Information: This work was made possible by the National Institutes of Health (NIH) through support of this work with Research Grant UO1 CA89566. The in vitro testing was conducted through the Developmental Therapeutics Program, DCTD, NCI under Contract NO1-CO-56000. This research was conducted in a facility constructed with support from Research Facilities Improvement Program Grant Number C06-14499 from the National Center for Research Resources of the National Institutes of Health. ",

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doi = "10.1016/j.bmcl.2005.03.101",

language = "English (US)",

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journal = "Bioorganic and Medicinal Chemistry Letters",

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AU - Xiao, Xiangshu

AU - Miao, Ze Hong

AU - Antony, Smitha

AU - Pommier, Yves

AU - Cushman, Mark

N1 - Funding Information: This work was made possible by the National Institutes of Health (NIH) through support of this work with Research Grant UO1 CA89566. The in vitro testing was conducted through the Developmental Therapeutics Program, DCTD, NCI under Contract NO1-CO-56000. This research was conducted in a facility constructed with support from Research Facilities Improvement Program Grant Number C06-14499 from the National Center for Research Resources of the National Institutes of Health.

PY - 2005/6/2

Y1 - 2005/6/2

N2 - Dihydroindenoisoquinolines are analogs of cytotoxic indenoisoquinoline topoisomerase I (Top1) inhibitors, exhibiting potent cytotoxicity but weak inhibitory activity toward Top1. Through COMPARE analysis, cytotoxicity studies in Top1-deficient cells, chemical synthesis and biological evaluation of methylated dihydroindenoisoquinoline 5, we demonstrated that dihydroindenoisoquinolines function as prodrugs of indenoisoquinolines in cancer cells.

AB - Dihydroindenoisoquinolines are analogs of cytotoxic indenoisoquinoline topoisomerase I (Top1) inhibitors, exhibiting potent cytotoxicity but weak inhibitory activity toward Top1. Through COMPARE analysis, cytotoxicity studies in Top1-deficient cells, chemical synthesis and biological evaluation of methylated dihydroindenoisoquinoline 5, we demonstrated that dihydroindenoisoquinolines function as prodrugs of indenoisoquinolines in cancer cells.

KW - Antitumor

KW - Dihydroindenoisoquinoline

KW - Indenoisoquinoline

KW - Prodrug

KW - Topoisomerase I

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JF - Bioorganic and Medicinal Chemistry Letters

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ER -

Dihydroindenoisoquinolines function as prodrugs of indenoisoquinolines

Abstract

Keywords

ASJC Scopus subject areas

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