Dimethoxybenzo[i]phenanthridine-12-carboxylic acid derivatives and 6H-dibenzo[c,h][2,6]naphthyridin-5-ones with potent topoisomerase I-targeting activity and cytotoxicity

Alexander L. Ruchelman; Shejin Zhu; Nai Zhou; Angela Liu; Leroy F. Liu; Edmond J. LaVoie

doi:10.1016/j.bmcl.2004.08.070

Dimethoxybenzo[i]phenanthridine-12-carboxylic acid derivatives and 6H-dibenzo[c,h][2,6]naphthyridin-5-ones with potent topoisomerase I-targeting activity and cytotoxicity

Alexander L. Ruchelman, Shejin Zhu, Nai Zhou, Angela Liu, Leroy F. Liu, Edmond J. LaVoie

Ernest Mario School of Pharmacy, Medicinal Chemistry

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

17 Scopus citations

Abstract

The exceptional TOP1-targeting activity and antitumor activity of ARC-111, 1, prompted studies on similarly substituted benzo[i]phenanthridine-12- carboxylic ester and amide derivatives. These studies were extended to include 6-substituted 8,9-dimethoxy-2,3-methylenedioxy-dibenzo[c,h][2,6]naphthyridin-5- ones, which represent reversed lactam analogues of 1. Several of these analogues retained the potent TOP1-targeting activity and cytotoxicity observed for ARC-111.

Original language	English (US)
Pages (from-to)	5585-5589
Number of pages	5
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	14
Issue number	22
DOIs	https://doi.org/10.1016/j.bmcl.2004.08.070
State	Published - Nov 15 2004

All Science Journal Classification (ASJC) codes

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

Keywords

Anticancer
Benzo[i]phenanthridines
Cytotoxic agents
Dibenzo[c,h]naphthyridines
Topoisomerase I

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10.1016/j.bmcl.2004.08.070

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title = "Dimethoxybenzo[i]phenanthridine-12-carboxylic acid derivatives and 6H-dibenzo[c,h][2,6]naphthyridin-5-ones with potent topoisomerase I-targeting activity and cytotoxicity",

abstract = "The exceptional TOP1-targeting activity and antitumor activity of ARC-111, 1, prompted studies on similarly substituted benzo[i]phenanthridine-12- carboxylic ester and amide derivatives. These studies were extended to include 6-substituted 8,9-dimethoxy-2,3-methylenedioxy-dibenzo[c,h][2,6]naphthyridin-5- ones, which represent reversed lactam analogues of 1. Several of these analogues retained the potent TOP1-targeting activity and cytotoxicity observed for ARC-111.",

keywords = "Anticancer, Benzo[i]phenanthridines, Cytotoxic agents, Dibenzo[c,h]naphthyridines, Topoisomerase I",

author = "Ruchelman, {Alexander L.} and Shejin Zhu and Nai Zhou and Angela Liu and Liu, {Leroy F.} and LaVoie, {Edmond J.}",

note = "Funding Information: This study was supported by Grant CA098127 (E.J.L.) and Grant CA39662 (L.F.L.) and Grant CA077433 (L.F.L.) from the National Cancer Institute.",

year = "2004",

month = nov,

day = "15",

doi = "10.1016/j.bmcl.2004.08.070",

language = "English (US)",

volume = "14",

pages = "5585--5589",

journal = "Bioorganic and Medicinal Chemistry Letters",

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Dimethoxybenzo[i]phenanthridine-12-carboxylic acid derivatives and 6H-dibenzo[c,h][2,6]naphthyridin-5-ones with potent topoisomerase I-targeting activity and cytotoxicity. / Ruchelman, Alexander L.; Zhu, Shejin; Zhou, Nai et al.
In: Bioorganic and Medicinal Chemistry Letters, Vol. 14, No. 22, 15.11.2004, p. 5585-5589.

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

TY - JOUR

T1 - Dimethoxybenzo[i]phenanthridine-12-carboxylic acid derivatives and 6H-dibenzo[c,h][2,6]naphthyridin-5-ones with potent topoisomerase I-targeting activity and cytotoxicity

AU - Ruchelman, Alexander L.

AU - Zhu, Shejin

AU - Zhou, Nai

AU - Liu, Angela

AU - Liu, Leroy F.

AU - LaVoie, Edmond J.

N1 - Funding Information: This study was supported by Grant CA098127 (E.J.L.) and Grant CA39662 (L.F.L.) and Grant CA077433 (L.F.L.) from the National Cancer Institute.

PY - 2004/11/15

Y1 - 2004/11/15

N2 - The exceptional TOP1-targeting activity and antitumor activity of ARC-111, 1, prompted studies on similarly substituted benzo[i]phenanthridine-12- carboxylic ester and amide derivatives. These studies were extended to include 6-substituted 8,9-dimethoxy-2,3-methylenedioxy-dibenzo[c,h][2,6]naphthyridin-5- ones, which represent reversed lactam analogues of 1. Several of these analogues retained the potent TOP1-targeting activity and cytotoxicity observed for ARC-111.

AB - The exceptional TOP1-targeting activity and antitumor activity of ARC-111, 1, prompted studies on similarly substituted benzo[i]phenanthridine-12- carboxylic ester and amide derivatives. These studies were extended to include 6-substituted 8,9-dimethoxy-2,3-methylenedioxy-dibenzo[c,h][2,6]naphthyridin-5- ones, which represent reversed lactam analogues of 1. Several of these analogues retained the potent TOP1-targeting activity and cytotoxicity observed for ARC-111.

KW - Anticancer

KW - Benzo[i]phenanthridines

KW - Cytotoxic agents

KW - Dibenzo[c,h]naphthyridines

KW - Topoisomerase I

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JO - Bioorganic and Medicinal Chemistry Letters

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ER -

Dimethoxybenzo[i]phenanthridine-12-carboxylic acid derivatives and 6H-dibenzo[c,h][2,6]naphthyridin-5-ones with potent topoisomerase I-targeting activity and cytotoxicity

Abstract

All Science Journal Classification (ASJC) codes

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