Antitumor agents. Part 226: synthesis and cytotoxicity of 2-phenyl-4-quinolone acetic acids and their esters.
2-Phenyl-4-quinolone acetic acids and their esters were synthesized and evaluated for interaction with tubulin and for cytotoxicity against a panel of human tumor cell lines. 2-Phenyl- and 2-(2'-fluorophenyl)-4-quinolone-8-acetic acids (11 and 12) displayed potent cytotoxicity with ED(50) values at nanomolar concentrations, but had minimal activity against tubulin polymerization. 2-(2'-Fluorophenyl)-4-quinolone-6-acetic acid (3) and 2-(2'-fluorophenyl)-4-quinolone-8-acetic acid methyl ester (10) moderately inhibited tubulin polymerization.
Xia
Yi
Y
Natural Products Laboratory, School of Pharmacy, University of North Carolina, Chapel Hill 27599, USA.
Yang
Zheng-Yu
ZY
Xia
Peng
P
Bastow
Kenneth F
KF
Nakanishi
Yuka
Y
Nampoothiri
Priya
P
Hamel
Ernest
E
Brossi
Arnold
A
Lee
Kuo-Hsiung
KH
D000085:Acetates / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004952:Esters; D006801:Humans; D020128:Inhibitory Concentration 50; D015363:Quinolones / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014404:Tubulin / Q000737:chemistry / Q000187:drug effects
D000085:Acetates; D000970:Antineoplastic Agents; D004952:Esters; D015363:Quinolones; D014404:Tubulin