Lignans from the bark of Machilus thunbergii and their DNA topoisomerases I and II inhibition and cytotoxicity

Biol Pharm Bull. 2004 Jul;27(7):1147-50. doi: 10.1248/bpb.27.1147.

Abstract

Activity-guided fractionation based on topoisomerase I inhibitory activity lead to the isolation of ten lignans (1-10) from the methylene chloride extract of the bark of Machilus thunbergii SIEB. et ZUCC. (Lauraceae). These were identified as machilin A (1), erythro-austrobailignan-6 (2), meso-monomethyl dihydroguaiaretic acid (3), meso-dihydroguaiaretic acid (4), galbacin (5), machilin F (6), nectandrin A (7) nectandrin B (8), (-)-acuminatin (9) and (7S,8S)-7-(4-hydroxy-3-methoxyphenyl)-1'-formyl-3'-methoxy-8-methyldihydrobenzofuran (10) by spectral evidence. In DNA topoisomerase I and II assays in vitro at a concentration of 100 microM, 4 showed the most potent inhibitory activity, 93.6 and 82.1% inhibition, respectively, and 8 showed 79.1 and 34.3% inhibition, respectively. All of these compounds exhibited weak or no cytotoxicities against either the human colon carcinoma cell line (HT-29) or the human breast carcinoma cell line (MCF-7).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cell Line, Tumor
  • DNA Topoisomerases, Type I / metabolism
  • DNA Topoisomerases, Type II / metabolism
  • Enzyme Inhibitors / isolation & purification
  • Enzyme Inhibitors / pharmacology
  • Enzyme Inhibitors / toxicity*
  • HT29 Cells
  • Humans
  • Lauraceae*
  • Lignans / isolation & purification
  • Lignans / pharmacology
  • Lignans / toxicity*
  • Plant Bark
  • Plant Extracts / isolation & purification
  • Plant Extracts / pharmacology
  • Plant Extracts / toxicity
  • Topoisomerase I Inhibitors*
  • Topoisomerase II Inhibitors*

Substances

  • Enzyme Inhibitors
  • Lignans
  • Plant Extracts
  • Topoisomerase I Inhibitors
  • Topoisomerase II Inhibitors
  • DNA Topoisomerases, Type I
  • DNA Topoisomerases, Type II