当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > Novel quinolinequinone antitumor agents: structure-metabolism studies with NAD(P)H:quinone oxidoreductase (NQO1).

Novel quinolinequinone antitumor agents: structure-metabolism studies with NAD(P)H:quinone oxidoreductase (NQO1).

Abstract：

:A series of quinolinequinones bearing various substituents has been synthesized, and the effects of substituents on the metabolism of the quinones by recombinant human NAD(P)H:quinone oxidoreductase (hNQO1) was studied. A range of quinolinequinones were selected for study, and were specifically designed to probe the effects of aryl substituents at C-2. A range of 28 quinolinequinones 2-29 was prepared using three general strategies: the palladium(0) catalyzed coupling of 2-chloroquinolines, the classical Friedländer synthesis and the double-Vilsmeier reaction of acetanilides. One example of an isoquinolinequinone 30 was also prepared, and the reduction potentials of the quinones were measured by cyclic voltammetry. For simple substituents R(2) at the quinoline 2-position, the rates of quinone metabolism by hNQO1 decrease for R(2)=Cl>H approximately Me>Ph. For aromatic substituents, the rate of reduction decreases dramatically for R(2)=Ph>1-naphthyl>2-naphthyl>4-biphenyl. Compounds containing a pyridine substituent are the best substrates, and the rates decrease as R(2)=4-pyridyl>3-pyridyl>2-pyridyl>4-methyl-2-pyridyl>5-methyl-2-pyridyl. The toxicity toward human colon carcinoma cells with either no detectable activity (H596 or BE-WT) or high NQO1 activity (H460 or BE-NQ) was also studied in representative quinones. Quinones that are good substrates for hNQO1 are more toxic to the NQO1 containing or expressing cell lines (H460 and BE-NQ) than the NQO1 deficient cell lines (H596 and BE-WT).

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Fryatt T,Pettersson HI,Gardipee WT,Bray KC,Green SJ,Slawin AM,Beall HD,Moody CJ

doi

10.1016/j.bmc.2004.01.021

subject

Has Abstract

pub_date

2004-04-01 00:00:00

pages

1667-87

issue

7

eissn

0968-0896

issn

1464-3391

pii

S0968089604000549

journal_volume

12

pub_type

杂志文章

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