12-Substituted 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridines as novel topoisomerase I-targeting antitumor agents

Wei Feng; Mavurapu Satyanarayana; Yuan Chin Tsai; Angela A. Liu; Leroy F. Liu; Edmond J. LaVoie

doi:10.1016/j.bmc.2009.02.023

12-Substituted 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridines as novel topoisomerase I-targeting antitumor agents

Wei Feng, Mavurapu Satyanarayana, Yuan Chin Tsai, Angela A. Liu, Leroy F. Liu, Edmond J. LaVoie

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

18 Citations (Scopus)

Abstract

2,3-Dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine and a few of its 12-substituted analogs are active as TOP1-targeting agents. Studies were performed to further evaluate the potential of this series of non-camptothecin TOP1-targeting agents. The influence of a hydroxymethyl, formyl, N,N-dimethylaminomethyl, 2-(N,N-dimethylamino)ethyl, 3-(N,N-dimethylamino)propyl), and 4-(N,N-dimethylamino)butyl substituent at the 12-position on TOP1-targeting activity and tumor cell growth was evaluated. In addition, the relative pharmacologic activities of the 12-carboxamide analog, as well as its N-methyl and N,N-dimethyl derivatives were assessed.

Original language	English
Pages (from-to)	2877-2885
Number of pages	9
Journal	Bioorganic and Medicinal Chemistry
Volume	17
Issue number	7
DOIs	https://doi.org/10.1016/j.bmc.2009.02.023
Publication status	Published - Apr 1 2009
Externally published	Yes

Keywords

Benzo[i]phenanthridines
Cytotoxicity
Structure-activity
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.bmc.2009.02.023

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@article{fc4cc95655cd49fdab252baaf63aaba3,

title = "12-Substituted 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridines as novel topoisomerase I-targeting antitumor agents",

abstract = "2,3-Dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine and a few of its 12-substituted analogs are active as TOP1-targeting agents. Studies were performed to further evaluate the potential of this series of non-camptothecin TOP1-targeting agents. The influence of a hydroxymethyl, formyl, N,N-dimethylaminomethyl, 2-(N,N-dimethylamino)ethyl, 3-(N,N-dimethylamino)propyl), and 4-(N,N-dimethylamino)butyl substituent at the 12-position on TOP1-targeting activity and tumor cell growth was evaluated. In addition, the relative pharmacologic activities of the 12-carboxamide analog, as well as its N-methyl and N,N-dimethyl derivatives were assessed.",

keywords = "Benzo[i]phenanthridines, Cytotoxicity, Structure-activity, Topoisomerase I",

author = "Wei Feng and Mavurapu Satyanarayana and Tsai, {Yuan Chin} and Liu, {Angela A.} and Liu, {Leroy F.} and LaVoie, {Edmond J.}",

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

year = "2009",

month = apr,

day = "1",

doi = "10.1016/j.bmc.2009.02.023",

language = "English",

volume = "17",

pages = "2877--2885",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

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T1 - 12-Substituted 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridines as novel topoisomerase I-targeting antitumor agents

AU - Feng, Wei

AU - Satyanarayana, Mavurapu

AU - Tsai, Yuan Chin

AU - Liu, Angela A.

AU - Liu, Leroy F.

AU - LaVoie, Edmond J.

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

PY - 2009/4/1

Y1 - 2009/4/1

N2 - 2,3-Dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine and a few of its 12-substituted analogs are active as TOP1-targeting agents. Studies were performed to further evaluate the potential of this series of non-camptothecin TOP1-targeting agents. The influence of a hydroxymethyl, formyl, N,N-dimethylaminomethyl, 2-(N,N-dimethylamino)ethyl, 3-(N,N-dimethylamino)propyl), and 4-(N,N-dimethylamino)butyl substituent at the 12-position on TOP1-targeting activity and tumor cell growth was evaluated. In addition, the relative pharmacologic activities of the 12-carboxamide analog, as well as its N-methyl and N,N-dimethyl derivatives were assessed.

AB - 2,3-Dimethoxy-8,9-methylenedioxybenzo[i]phenanthridine and a few of its 12-substituted analogs are active as TOP1-targeting agents. Studies were performed to further evaluate the potential of this series of non-camptothecin TOP1-targeting agents. The influence of a hydroxymethyl, formyl, N,N-dimethylaminomethyl, 2-(N,N-dimethylamino)ethyl, 3-(N,N-dimethylamino)propyl), and 4-(N,N-dimethylamino)butyl substituent at the 12-position on TOP1-targeting activity and tumor cell growth was evaluated. In addition, the relative pharmacologic activities of the 12-carboxamide analog, as well as its N-methyl and N,N-dimethyl derivatives were assessed.

KW - Benzo[i]phenanthridines

KW - Cytotoxicity

KW - Structure-activity

KW - Topoisomerase I

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JO - Bioorganic and Medicinal Chemistry

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ER -

12-Substituted 2,3-dimethoxy-8,9-methylenedioxybenzo[i]phenanthridines as novel topoisomerase I-targeting antitumor agents

Abstract

Keywords

ASJC Scopus subject areas

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