title: Lupane derivatives from Lophopetalum wallichii with farnesyl protein transferase inhibitory activity.
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.
authors: Department of Medicinal Chemistry and Pharmacognosy, College of Pharmacy, University of Illinois at Chicago 60612, USA.
authors: S
authors: S
authors: Sturm
authors: R R
authors: RR
authors: Gil
authors: H B
authors: HB
authors: Chai
authors: O D
authors: OD
authors: Ngassapa
authors: T
authors: T
authors: Santisuk
authors: V
authors: V
authors: Reutrakul
authors: A
authors: A
authors: Howe
authors: M
authors: M
authors: Moss
authors: J M
authors: JM
authors: Besterman
authors: S L
authors: SL
authors: Yang
authors: J E
authors: JE
authors: Farthing
authors: R M
authors: RM
authors: Tait
authors: J A
authors: JA
authors: Lewis
authors: M J
authors: MJ
authors: O'Neill
authors: N R
authors: NR
authors: Farnsworth
authors: G A
authors: GA
authors: Cordell
authors: J M
authors: JM
authors: Pezzuto
authors: A D
authors: AD
authors: Kinghorn
mesh_terms: D019883:Alkyl and Aryl Transferases; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D018547:Plant Stems / Q000737:chemistry*; D010946:Plants, Medicinal / Q000737:chemistry*; D014166:Transferases / Q000037:antagonists & inhibitors*; D014315:Triterpenes / Q000302:isolation & purification* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D004791:Enzyme Inhibitors; D014315:Triterpenes; D014166:Transferases; D019883:Alkyl and Aryl Transferases; C064911:p21(ras) farnesyl-protein transferase