Synthetic secofriedelane and friedelane derivatives as inhibitors of human lymphocyte proliferation and growth of human cancer cell lines in vitro.
Controlled silylation of friedelin (1) from cork smoker wash solids, a byproduct generated during processing of corkboard by steam baking, gave 3-trimethylsiloxyfriedel-2-ene (3) in high yields. Oxidation of 3 with OsO(4)/NMMO produced 2alpha-hydroxyfriedelan-3-one (cerin) (5), from which the new 2,3-secofriedelan-2-al-3-oic acid (6) was obtained quantitatively by periodic acid oxidation. Oxidation of 3 with DDQ afforded friedel-1-en-3-one (8). Reductive ozonolysis of 3 gave 2alpha,3beta-dihydroxyfriedelane, pachysandiol A (7). Compound 6 proved to be a potent inhibitor of human lymphocyte proliferation (IC(50) = 10.7 microM) and of the growth of a human cancer cell line (GI(50) = 5.4-17.2 microM). (13)C NMR data for compounds (3, 4, 5, 6a,7, and 8) are described for the first time.
Moiteiro
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INETI-Instituto Nacional de Engenharia e Tecnologia Industrial, Departamento de Tecnologia de Indústrias Químicas, Serviço de Química Fina, Estrada do Paço do Lumiar, 1649-038 Lisbon, Portugal. cristina.moiteiro@mail.ineti.pt
Justino
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Tavares
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Marcelo-Curto
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Florêncio
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Nascimento
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Pedro
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Cerqueira
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D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001932:Brain Neoplasms; D001943:Breast Neoplasms; D002855:Chromatography, Thin Layer; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D007680:Kidney Neoplasms; D008175:Lung Neoplasms; D008214:Lymphocytes / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D008545:Melanoma; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011174:Portugal; D029963:Quercus / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014315:Triterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D014407:Tumor Cells, Cultured / Q000187:drug effects
C439991:2,3-secofriedelan-2-al-3-oic acid; C439990:2-hydroxyfriedelan-3-one; C439989:3-trimethylsiloxyfriedel-2-ene; D000972:Antineoplastic Agents, Phytogenic; D014315:Triterpenes; C439992:friedel-1-en-3-one; C421805:friedelane