title: 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.
authors.affiliation: Graduate Institute of Pharmaceutical Chemistry, China Medical University, Taichung 40402, Taiwan, ROC.
authors.forename: Yung-Yi
authors.initials: YY
authors.lastname: Cheng
authors.forename: Chin-Yu
authors.initials: CY
authors.lastname: Liu
authors.forename: Meng-Tung
authors.initials: MT
authors.lastname: Tsai
authors.forename: Hui-Yi
authors.initials: HY
authors.lastname: Lin
authors.forename: Jai-Sing
authors.initials: JS
authors.lastname: Yang
authors.forename: Tian-Shung
authors.initials: TS
authors.lastname: Wu
authors.forename: Sheng-Chu
authors.initials: SC
authors.lastname: Kuo
authors.forename: Li-Jiau
authors.initials: LJ
authors.lastname: Huang
authors.forename: Kuo-Hsiung
authors.initials: KH
authors.lastname: Lee
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D015394:Molecular Structure; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D015363:Quinolones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C587421:2-(3-hydroxy-5-methoxyphenyl)-6-pyrrolidinylquinolin-4-one; D000970:Antineoplastic Agents; D011759:Pyrrolidines; D015363:Quinolones
keywords: 2-(Hydroxyphenyl)quinolin-4-one derivatives; Anticancer lead development; Antiproliferative activity; Prodrug
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