Novel topoisomerase I-targeting antitumor agents synthesized from the N,N,N-trimethylammonium derivative of ARC-111, 5H-2,3-dimethoxy-8,9-methylenedioxy-5-[(2-N,N,N-trimethylammonium)ethyl]dibenzo[c,h][1,6]naphthyridin-6-one iodide

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

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Several new TOP1-targeting agents were prepared using as an intermediate the N,N,N-trimethyl quaternary ammonium salt 2 of ARC-111. Direct displacement of the quaternary ammonium group with hydroxide, cyclopropylamine, imidazole, 1H-1,2,3-triazole, alkylethylenediamines, ethanolamine, and polyhydroxylated alkylamines provides a convenient means for furthering insight into the structure-activity relationships within this series of non-camptothecin TOP1-targeting agents. The relative TOP1-targeting activities and cytotoxicities were evaluated in RPMI8402 and P388 cells and their camptothecin-resistant variants. Their potential to serve as substrates for the efflux transporters MDR1 and BCRP, which are associated with multidrug resistance, was also assessed.

Original languageEnglish
Pages (from-to)3433-3438
Number of pages6
JournalEuropean Journal of Medicinal Chemistry
Volume44
Issue number9
DOIs
Publication statusPublished - Sep 2009
Externally publishedYes

Fingerprint

Type I DNA Topoisomerase
Iodides
Ammonium Compounds
Antineoplastic Agents
Derivatives
Camptothecin
Ethanolamine
Triazoles
Multiple Drug Resistance
Structure-Activity Relationship
Cytotoxicity
Salts
Substrates
topovale
cyclopropylamine
imidazole
hydroxide ion

Keywords

  • 5H-Dibenzo[c,h][1,6]naphthyridin-6-ones
  • Antitumor
  • ARC-111
  • Cytotoxic activity
  • Multidrug resistance
  • Quaternary ammonium salts
  • TOP1-targeting agents

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

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title = "Novel topoisomerase I-targeting antitumor agents synthesized from the N,N,N-trimethylammonium derivative of ARC-111, 5H-2,3-dimethoxy-8,9-methylenedioxy-5-[(2-N,N,N-trimethylammonium)ethyl]dibenzo[c,h][1,6]naphthyridin-6-one iodide",
abstract = "Several new TOP1-targeting agents were prepared using as an intermediate the N,N,N-trimethyl quaternary ammonium salt 2 of ARC-111. Direct displacement of the quaternary ammonium group with hydroxide, cyclopropylamine, imidazole, 1H-1,2,3-triazole, alkylethylenediamines, ethanolamine, and polyhydroxylated alkylamines provides a convenient means for furthering insight into the structure-activity relationships within this series of non-camptothecin TOP1-targeting agents. The relative TOP1-targeting activities and cytotoxicities were evaluated in RPMI8402 and P388 cells and their camptothecin-resistant variants. Their potential to serve as substrates for the efflux transporters MDR1 and BCRP, which are associated with multidrug resistance, was also assessed.",
keywords = "5H-Dibenzo[c,h][1,6]naphthyridin-6-ones, Antitumor, ARC-111, Cytotoxic activity, Multidrug resistance, Quaternary ammonium salts, TOP1-targeting agents",
author = "Wei Feng and Mavurapu Satyanarayana and Tsai, {Yuan Chin} and Liu, {Angela A.} and Liu, {Leroy F.} and LaVoie, {Edmond J.}",
year = "2009",
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AU - Feng, Wei

AU - Satyanarayana, Mavurapu

AU - Tsai, Yuan Chin

AU - Liu, Angela A.

AU - Liu, Leroy F.

AU - LaVoie, Edmond J.

PY - 2009/9

Y1 - 2009/9

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KW - Cytotoxic activity

KW - Multidrug resistance

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KW - TOP1-targeting agents

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