Syntheses and biological evaluation of topoisomerase I-targeting agents related to 11-[2-(N,N-dimethylamino)ethyl]-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-one (ARC-31)

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

研究成果: 雜誌貢獻文章

11 引文 (Scopus)

摘要

Several 11-ethyl-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-ones with varied functionality on the ethyl substituent have exhibited potent topoisomerase I (TOP1) targeting activity and antitumor activity. The influence of various polar substituents at the 2-position of the 11-ethyl substituent, including N-methylamine, N-isopropylamine, hydroxyl, and hydroxylamino groups, on TOP1-targeting activity and cytotoxicity was assessed. The N-methylamine and N-isopropylamine derivatives were also evaluated as antitumor agents in athymic nude mice with MDA-MB-435 human tumor xenografts. Both compounds were active as antitumor agents upon either parenteral or oral administration.
原文英語
頁(從 - 到)7824-7831
頁數8
期刊Bioorganic and Medicinal Chemistry
16
發行號16
DOIs
出版狀態已發佈 - 八月 15 2008
對外發佈Yes

指紋

Type I DNA Topoisomerase
Nude Mice
Antineoplastic Agents
Cytotoxicity
Heterografts
Hydroxyl Radical
Oral Administration
Tumors
Derivatives
Neoplasms
12-aza-5H-8,9-dimethoxy-5-(2-(N,N-dimethylamino)ethyl)-2,3-methylenedioxydibenzo(c,h)(1,6)naphthyridin-6-one
2-propylamine
methylamine

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Organic Chemistry
  • Drug Discovery
  • Pharmaceutical Science

引用此文

Syntheses and biological evaluation of topoisomerase I-targeting agents related to 11-[2-(N,N-dimethylamino)ethyl]-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-one (ARC-31). / Satyanarayana, Mavurapu; Feng, Wei; Cheng, Liang; Liu, Angela A.; Tsai, Yuan Chin; Liu, Leroy F.; LaVoie, Edmond J.

於: Bioorganic and Medicinal Chemistry, 卷 16, 編號 16, 15.08.2008, p. 7824-7831.

研究成果: 雜誌貢獻文章

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title = "Syntheses and biological evaluation of topoisomerase I-targeting agents related to 11-[2-(N,N-dimethylamino)ethyl]-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-one (ARC-31)",
abstract = "Several 11-ethyl-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-ones with varied functionality on the ethyl substituent have exhibited potent topoisomerase I (TOP1) targeting activity and antitumor activity. The influence of various polar substituents at the 2-position of the 11-ethyl substituent, including N-methylamine, N-isopropylamine, hydroxyl, and hydroxylamino groups, on TOP1-targeting activity and cytotoxicity was assessed. The N-methylamine and N-isopropylamine derivatives were also evaluated as antitumor agents in athymic nude mice with MDA-MB-435 human tumor xenografts. Both compounds were active as antitumor agents upon either parenteral or oral administration.",
keywords = "Antitumor, Athymic mice, Cinnolines, Cytotoxicity, Human tumor xenografts, Isoquino[4,3-c]cinnolin-12-ones, Multidrug resistance, Topoisomerase",
author = "Mavurapu Satyanarayana and Wei Feng and Liang Cheng and Liu, {Angela A.} and Tsai, {Yuan Chin} and Liu, {Leroy F.} and LaVoie, {Edmond J.}",
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AU - Satyanarayana, Mavurapu

AU - Feng, Wei

AU - Cheng, Liang

AU - Liu, Angela A.

AU - Tsai, Yuan Chin

AU - Liu, Leroy F.

AU - LaVoie, Edmond J.

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N2 - Several 11-ethyl-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-ones with varied functionality on the ethyl substituent have exhibited potent topoisomerase I (TOP1) targeting activity and antitumor activity. The influence of various polar substituents at the 2-position of the 11-ethyl substituent, including N-methylamine, N-isopropylamine, hydroxyl, and hydroxylamino groups, on TOP1-targeting activity and cytotoxicity was assessed. The N-methylamine and N-isopropylamine derivatives were also evaluated as antitumor agents in athymic nude mice with MDA-MB-435 human tumor xenografts. Both compounds were active as antitumor agents upon either parenteral or oral administration.

AB - Several 11-ethyl-2,3-dimethoxy-8,9-methylenedioxy-11H-isoquino[4,3-c]cinnolin-12-ones with varied functionality on the ethyl substituent have exhibited potent topoisomerase I (TOP1) targeting activity and antitumor activity. The influence of various polar substituents at the 2-position of the 11-ethyl substituent, including N-methylamine, N-isopropylamine, hydroxyl, and hydroxylamino groups, on TOP1-targeting activity and cytotoxicity was assessed. The N-methylamine and N-isopropylamine derivatives were also evaluated as antitumor agents in athymic nude mice with MDA-MB-435 human tumor xenografts. Both compounds were active as antitumor agents upon either parenteral or oral administration.

KW - Antitumor

KW - Athymic mice

KW - Cinnolines

KW - Cytotoxicity

KW - Human tumor xenografts

KW - Isoquino[4,3-c]cinnolin-12-ones

KW - Multidrug resistance

KW - Topoisomerase

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