title: First total synthesis of protoapigenone and its analogues as potent cytotoxic agents.
abstract: Protoapigenone (1), isolated from Thelypteris torresiana, previously showed significant cytotoxic activity against five human cancer cell lines. In a continued structure-activity relationship study, the first total synthesis and modification of 1 were achieved. All synthesized compounds and related intermediates were evaluated for cytotoxic activity against five human cancer cell lines, HepG2, Hep3B, MDA-MB-231, MCF-7, and A549. Among them, 24 showed 2.2-14.2-fold greater cytotoxicity than 1 and naphthyl A-ring analogues remarkably enhanced the activity.
authors.affiliation: Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
authors.forename: An-Shen
authors.initials: AS
authors.lastname: Lin
authors.forename: Kyoko
authors.initials: K
authors.lastname: Nakagawa-Goto
authors.forename: Fang-Rong
authors.initials: FR
authors.lastname: Chang
authors.forename: Donglei
authors.initials: D
authors.lastname: Yu
authors.forename: Susan L
authors.initials: SL
authors.lastname: Morris-Natschke
authors.forename: Chin-Chung
authors.initials: CC
authors.lastname: Wu
authors.forename: Shu-Li
authors.initials: SL
authors.lastname: Chen
authors.forename: Yang-Chang
authors.initials: YC
authors.lastname: Wu
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; D003512:Cyclohexanones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D047309:Flavones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005419:Flavonoids / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D013329:Structure-Activity Relationship
chemical_list: C524113:5-hydroxy-2-(1-hydroxy-4-oxocyclohexa-2,5-dienyl)-7-methoxy-4H-chromen-4-one; D000970:Antineoplastic Agents; D003512:Cyclohexanones; D047309:Flavones; D005419:Flavonoids; C524112:protoapigenone