Synthesis and biological relationships of 3',6-substituted 2-phenyl-4-quinolone-3-carboxylic acid derivatives as antimitotic agents.

Abstract:

:As part of a continuing search for potential anticancer drug candidates in the 2-phenyl-4-quinolone series, 3',6-substituted 2-phenyl-4-quinolone-3-carboxylic acid derivatives and their salts were synthesized and evaluated. Preliminary screening showed that carboxylic acid analogs containing a m-fluoro substituted 2-phenyl group displayed the highest in vitro anticancer activity. Activity decreased significantly if a chlorine or methoxy group replaced the fluorine atom. 3'-Fluoro-6-methoxy-2-phenyl-4-quinolone-3-carboxylic acid (68) had the highest in vitro cytotoxic activity among all tested carboxylic acid derivatives and their salts. The mechanism of action may be similar, but not identical, to that of tubulin binding drugs, such as navelbine and taxol. Compound 68 merits further investigation as a novel hydrophilic antimitotic agent.

journal_name

Bioorg Med Chem

authors

Lai YY,Huang LJ,Lee KH,Xiao Z,Bastow KF,Yamori T,Kuo SC

doi

10.1016/j.bmc.2004.09.041

subject

Has Abstract

pub_date

2005-01-03 00:00:00

pages

265-75

issue

1

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(04)00738-2

journal_volume

13

pub_type

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