Lupane derivatives from Lophopetalum wallichii with farnesyl protein transferase inhibitory activity

J Nat Prod. 1996 Jul;59(7):658-63. doi: 10.1021/np960370u.

Abstract

Chloroform-soluble extracts of the stems and of the mixed stems and stem bark of Lophopetalum wallichii were found to be inhibitory in a farnesyl protein transferase (FPTase) bioassay system. During the course of activity-guided fractionation, the known lupane-type triterpenes, ochraceolide A (1), ochraceolide B (2), betulin, and lupeol and the new lupane lactone, dihydro ochraceolide A (4), were isolated. The stereochemistry of the epoxide group of ochraceolide B (2) was determined by preparation of both epoxide isomers [2, and the new semisynthetic derivative, 20-epi-ochraceolide B (3)] from 1. The structure of 4 was established by reduction of 1 with sodium borohydride. Compounds 1 and 2 exhibited significant inhibitory activity in the FPTase assay (IC50 values of 1.0 and 0.7 microgram/mL, respectively). Lupeol was found to be weakly active (IC50 65.0 micrograms/mL) in this test system, whereas no significant inhibition was detected for betulin or compounds 3 or 4. When evaluated against a panel of human cancer cells in culture, compounds 1 and 4 were modestly cytotoxic. Compounds 2 and 3 were not active in the panel.

Publication types

  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkyl and Aryl Transferases*
  • Drug Screening Assays, Antitumor
  • Enzyme Inhibitors / isolation & purification*
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Magnetic Resonance Spectroscopy
  • Models, Molecular
  • Plant Stems / chemistry*
  • Plants, Medicinal / chemistry*
  • Transferases / antagonists & inhibitors*
  • Triterpenes / isolation & purification*
  • Triterpenes / pharmacology
  • Tumor Cells, Cultured

Substances

  • Enzyme Inhibitors
  • Triterpenes
  • Transferases
  • Alkyl and Aryl Transferases
  • p21(ras) farnesyl-protein transferase