Cytotoxicity and TOP1-targeting activity of 8- and 9-amino derivatives of 5-butyl- and 5-(2-N,N-dimethylamino)ethyl-5H-dibenzo[c,h][1,6]naphthyridin-6-ones

Lisa Sharma, Yuan Chin Tsai, Angela A. Liu, Leroy F. Liu, Edmond J. LaVoie

Research output: Contribution to journalArticle

7 Citations (Scopus)

Abstract

Studies on substituted 5H-dibenzo[c,h][1,6]naphthyridin-6-ones and 6H-dibenzo[c,h][2,6]naphthyridin-5-ones have demonstrated that hydrophilic substituents at the 2-position of an ethyl group at the 5- and 6-positions, respectively, can enhance biological activity. The compatibility of such hydrophilic groups at other sites with either TOP1-targeting activity or potent cytotoxic activity has not been explored. The present study examines the influence on biological activity of either a 2-(N,N-dimethylamino)ethyl or a N,N-dimethylacetamide derivative of 8- or 9-amino-5H-dibenzo[c,h]naphthyridin-6-ones that have a 5-butyl- or 5-[2-(N,N-dimethylamino)ethyl]-substituent.

Original languageEnglish
Pages (from-to)1471-1476
Number of pages6
JournalEuropean Journal of Medicinal Chemistry
Volume44
Issue number4
DOIs
Publication statusPublished - Apr 2009
Externally publishedYes

Fingerprint

Cytotoxicity
Bioactivity
Derivatives
dimethylacetamide

Keywords

  • 5H-Dibenzo[c,h][1,6]naphthyridin-6-ones
  • Cytotoxicity
  • Multidrug resistance
  • Topoisomerase I-targeting agents

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

@article{02fe72597d594ca0912b359d1ace1ce4,
title = "Cytotoxicity and TOP1-targeting activity of 8- and 9-amino derivatives of 5-butyl- and 5-(2-N,N-dimethylamino)ethyl-5H-dibenzo[c,h][1,6]naphthyridin-6-ones",
abstract = "Studies on substituted 5H-dibenzo[c,h][1,6]naphthyridin-6-ones and 6H-dibenzo[c,h][2,6]naphthyridin-5-ones have demonstrated that hydrophilic substituents at the 2-position of an ethyl group at the 5- and 6-positions, respectively, can enhance biological activity. The compatibility of such hydrophilic groups at other sites with either TOP1-targeting activity or potent cytotoxic activity has not been explored. The present study examines the influence on biological activity of either a 2-(N,N-dimethylamino)ethyl or a N,N-dimethylacetamide derivative of 8- or 9-amino-5H-dibenzo[c,h]naphthyridin-6-ones that have a 5-butyl- or 5-[2-(N,N-dimethylamino)ethyl]-substituent.",
keywords = "5H-Dibenzo[c,h][1,6]naphthyridin-6-ones, Cytotoxicity, Multidrug resistance, Topoisomerase I-targeting agents",
author = "Lisa Sharma and Tsai, {Yuan Chin} and Liu, {Angela A.} and Liu, {Leroy F.} and LaVoie, {Edmond J.}",
year = "2009",
month = "4",
doi = "10.1016/j.ejmech.2008.09.048",
language = "English",
volume = "44",
pages = "1471--1476",
journal = "European Journal of Medicinal Chemistry",
issn = "0223-5234",
publisher = "Elsevier Masson SAS",
number = "4",

}

TY - JOUR

T1 - Cytotoxicity and TOP1-targeting activity of 8- and 9-amino derivatives of 5-butyl- and 5-(2-N,N-dimethylamino)ethyl-5H-dibenzo[c,h][1,6]naphthyridin-6-ones

AU - Sharma, Lisa

AU - Tsai, Yuan Chin

AU - Liu, Angela A.

AU - Liu, Leroy F.

AU - LaVoie, Edmond J.

PY - 2009/4

Y1 - 2009/4

N2 - Studies on substituted 5H-dibenzo[c,h][1,6]naphthyridin-6-ones and 6H-dibenzo[c,h][2,6]naphthyridin-5-ones have demonstrated that hydrophilic substituents at the 2-position of an ethyl group at the 5- and 6-positions, respectively, can enhance biological activity. The compatibility of such hydrophilic groups at other sites with either TOP1-targeting activity or potent cytotoxic activity has not been explored. The present study examines the influence on biological activity of either a 2-(N,N-dimethylamino)ethyl or a N,N-dimethylacetamide derivative of 8- or 9-amino-5H-dibenzo[c,h]naphthyridin-6-ones that have a 5-butyl- or 5-[2-(N,N-dimethylamino)ethyl]-substituent.

AB - Studies on substituted 5H-dibenzo[c,h][1,6]naphthyridin-6-ones and 6H-dibenzo[c,h][2,6]naphthyridin-5-ones have demonstrated that hydrophilic substituents at the 2-position of an ethyl group at the 5- and 6-positions, respectively, can enhance biological activity. The compatibility of such hydrophilic groups at other sites with either TOP1-targeting activity or potent cytotoxic activity has not been explored. The present study examines the influence on biological activity of either a 2-(N,N-dimethylamino)ethyl or a N,N-dimethylacetamide derivative of 8- or 9-amino-5H-dibenzo[c,h]naphthyridin-6-ones that have a 5-butyl- or 5-[2-(N,N-dimethylamino)ethyl]-substituent.

KW - 5H-Dibenzo[c,h][1,6]naphthyridin-6-ones

KW - Cytotoxicity

KW - Multidrug resistance

KW - Topoisomerase I-targeting agents

UR - http://www.scopus.com/inward/record.url?scp=61349125497&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=61349125497&partnerID=8YFLogxK

U2 - 10.1016/j.ejmech.2008.09.048

DO - 10.1016/j.ejmech.2008.09.048

M3 - Article

VL - 44

SP - 1471

EP - 1476

JO - European Journal of Medicinal Chemistry

JF - European Journal of Medicinal Chemistry

SN - 0223-5234

IS - 4

ER -