Lupane Derivatives from Lophopetalum wallichii with Farnesyl Protein Transferase Inhibitory Activity

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), o...

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Veröffentlicht in:Journal of natural products (Washington, D.C.) D.C.), 1996-07, Vol.59 (7), p.658-663
Hauptverfasser: Sturm, Sonja, Gil, Roberto R, Chai, Hee-Byung, Ngassapa, Olipa D, Santisuk, Thawatchai, Reutrakul, Vichai, Howe, Anne, Moss, Marcia, Besterman, Jeffrey M, Yang, Shi-Lin, Farthing, John E, Tait, R. Murray, Lewis, Jane A, O'Neill, Melanie J, Farnsworth, Norman R, Cordell, Geoffrey A, Pezzuto, John M, Kinghorn, A. Douglas
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Sprache:eng
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Zusammenfassung: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 μg/mL, respectively). Lupeol was found to be weakly active (IC50 65.0 μg/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.
ISSN:0163-3864
1520-6025
DOI:10.1021/np960370u