1. Synthetic Secofriedelane and Friedelane Derivatives as Inhibitors of Human Lymphocyte Proliferation and Growth of Human Cancer Cell Lines in Vitro
- Author
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M. J. Marcelo-Curto, Madalena Pinto, R. Tavares, M. H. Florêncio, Nascimento Ms, Fátima Cerqueira, F. Justino, Cristina Moiteiro, and Madalena Pedro
- Subjects
Lung Neoplasms ,Magnetic Resonance Spectroscopy ,Silylation ,Carboxylic acid ,Friedelin ,Pharmaceutical Science ,Breast Neoplasms ,Chemical synthesis ,Aldehyde ,Analytical Chemistry ,Inhibitory Concentration 50 ,Quercus ,Structure-Activity Relationship ,chemistry.chemical_compound ,Drug Discovery ,Tumor Cells, Cultured ,Humans ,Organic chemistry ,Lymphocytes ,Cytotoxicity ,Melanoma ,Pharmacology ,chemistry.chemical_classification ,Ozonolysis ,Dose-Response Relationship, Drug ,Molecular Structure ,Portugal ,Brain Neoplasms ,Organic Chemistry ,Periodic acid ,Antineoplastic Agents, Phytogenic ,Kidney Neoplasms ,Triterpenes ,Complementary and alternative medicine ,chemistry ,Molecular Medicine ,Chromatography, Thin Layer ,Drug Screening Assays, Antitumor ,Oxidation-Reduction ,Nuclear chemistry - Abstract
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.
- Published
- 2001