First total synthesis of protoapigenone and its analogues as potent cytotoxic agents

J Med Chem. 2007 Aug 9;50(16):3921-7. doi: 10.1021/jm070363a. Epub 2007 Jul 10.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cyclohexanones / chemical synthesis*
  • Cyclohexanones / chemistry
  • Cyclohexanones / pharmacology
  • Drug Screening Assays, Antitumor
  • Flavones / chemical synthesis*
  • Flavones / chemistry
  • Flavones / pharmacology
  • Flavonoids / chemical synthesis*
  • Flavonoids / chemistry
  • Flavonoids / pharmacology
  • Humans
  • Structure-Activity Relationship

Substances

  • 5-hydroxy-2-(1-hydroxy-4-oxocyclohexa-2,5-dienyl)-7-methoxy-4H-chromen-4-one
  • Antineoplastic Agents
  • Cyclohexanones
  • Flavones
  • Flavonoids
  • protoapigenone