Lupane Derivatives from Lophopetalum wallichii with Farnesyl Protein Transferase Inhibitory Activity
| Autor: | J. A. Lewis, John M. Pezzuto, T. Santisuk, R M Tait, A Howe, Roberto R. Gil, Olipa Ngassapa, Vichai Reutrakul, Norman R. Farnsworth, Shu-Wei Yang, J M Besterman, M J O'Neill, Heebyung Chai, J E Farthing, S Sturm, A. D. Kinghorn, M Moss, Geoffrey A. Cordell |
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| Rok vydání: | 1996 |
| Předmět: |
Models
Molecular Magnetic Resonance Spectroscopy Farnesyl Protein Transferase Stereochemistry Pharmaceutical Science Pharmacognosy Analytical Chemistry chemistry.chemical_compound Triterpene Transferases Drug Discovery Tumor Cells Cultured Humans Enzyme Inhibitors Lupeol Pharmacology chemistry.chemical_classification Farnesyl-diphosphate farnesyltransferase Alkyl and Aryl Transferases Plants Medicinal Betulin Plant Stems Organic Chemistry Biological activity Triterpenes Complementary and alternative medicine chemistry Molecular Medicine Drug Screening Assays Antitumor Lactone |
| Zdroj: | Journal of Natural Products. 59:658-663 |
| ISSN: | 1520-6025 0163-3864 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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