6-Substituted 6H-dibenzo[c,h][2,6]naphthyridin-5-ones: Reversed lactam analogues of ARC-111 with potent topoisomerase I-targeting activity and cytotoxicity

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

研究成果: 雜誌貢獻文章

22 引文 (Scopus)

摘要

6-Substituted 8,9-dimethoxy-2,3-methylenedioxy-6H-dibenzo[c,h][2,6] naphthyridin-5-ones were synthesized and evaluated for topoisomerase I-targeting activity and cytotoxicity. Several of these reversed lactam analogues of ARC-111 exhibited exceptional cytotoxicity with IC50 values ranging from 0.5 to 3.0 nM. In contrast to topotecan, no resistance was observed with several of these reversed lactam analogues in tumor cell lines that overexpressed the efflux transporters MDR1 or BCRP.

原文英語
頁(從 - 到)3131-3143
頁數13
期刊Bioorganic and Medicinal Chemistry
14
發行號9
DOIs
出版狀態已發佈 - 五月 1 2006
對外發佈Yes

指紋

Lactams
Type I DNA Topoisomerase
Cytotoxicity
Topotecan
Tumor Cell Line
Inhibitory Concentration 50
Tumors
Cells
topovale

ASJC Scopus subject areas

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

引用此文

6-Substituted 6H-dibenzo[c,h][2,6]naphthyridin-5-ones : Reversed lactam analogues of ARC-111 with potent topoisomerase I-targeting activity and cytotoxicity. / Zhu, Shejin; Ruchelman, Alexander L.; Zhou, Nai; Liu, Angela; Liu, Leroy-Fong; LaVoie, Edmond J.

於: Bioorganic and Medicinal Chemistry, 卷 14, 編號 9, 01.05.2006, p. 3131-3143.

研究成果: 雜誌貢獻文章

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abstract = "6-Substituted 8,9-dimethoxy-2,3-methylenedioxy-6H-dibenzo[c,h][2,6] naphthyridin-5-ones were synthesized and evaluated for topoisomerase I-targeting activity and cytotoxicity. Several of these reversed lactam analogues of ARC-111 exhibited exceptional cytotoxicity with IC50 values ranging from 0.5 to 3.0 nM. In contrast to topotecan, no resistance was observed with several of these reversed lactam analogues in tumor cell lines that overexpressed the efflux transporters MDR1 or BCRP.",
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AU - Zhu, Shejin

AU - Ruchelman, Alexander L.

AU - Zhou, Nai

AU - Liu, Angela

AU - Liu, Leroy-Fong

AU - LaVoie, Edmond J.

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