First total synthesis of protoapigenone and its analogues as potent cytotoxic agents.
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.
Lin
An-Shen
AS
Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Nakagawa-Goto
Kyoko
K
Chang
Fang-Rong
FR
Yu
Donglei
D
Morris-Natschke
Susan L
SL
Wu
Chin-Chung
CC
Chen
Shu-Li
SL
Wu
Yang-Chang
YC
Lee
Kuo-Hsiung
KH
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
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