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Design, synthesis, and mechanism of action of 2-(3-hydroxy-5-methoxyphenyl)-6-pyrrolidinylquinolin-4-one as a potent anticancer lead.

ABSTRACT: New 6- (or 6,7-) substituted 2-(hydroxyl substituted phenyl)quinolin-4-one derivatives were synthesized and screened for antiproliferative effects against cancer cell lines. Structure-activity relationship correlations were established and the most promising compound 2-(3-hydroxy-5-methoxyphenyl)-6-pyrrolidin-1-ylquinolin-4-one (6h) exhibited strong inhibitory activity against various human cancer cell lines, particularly non-small cell lung cancer NCI-H522. Additional studies suggested a mechanism of action resembling that of the antimitotic drug vincristine. The presence of a C-ring OH group in 6h will allow this compound to be converted readily to a water soluble and physicochemically stable hydrophilic prodrug. Compound 6h is proposed as a new anticancer lead compound.

SUBMITTER: Cheng YY

PROVIDER: S-EPMC3773863 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Design, synthesis, and mechanism of action of 2-(3-hydroxy-5-methoxyphenyl)-6-pyrrolidinylquinolin-4-one as a potent anticancer lead.

Cheng Yung-Yi YY Liu Chin-Yu CY Tsai Meng-Tung MT Lin Hui-Yi HY Yang Jai-Sing JS Wu Tian-Shung TS Kuo Sheng-Chu SC Huang Li-Jiau LJ Lee Kuo-Hsiung KH

Bioorganic & medicinal chemistry letters 20130704 18

New 6- (or 6,7-) substituted 2-(hydroxyl substituted phenyl)quinolin-4-one derivatives were synthesized and screened for antiproliferative effects against cancer cell lines. Structure-activity relationship correlations were established and the most promising compound 2-(3-hydroxy-5-methoxyphenyl)-6-pyrrolidin-1-ylquinolin-4-one (6h) exhibited strong inhibitory activity against various human cancer cell lines, particularly non-small cell lung cancer NCI-H522. Additional studies suggested a mechan ...[more]

PMID: 23916255

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