title: Absolute Configuration of Dihydro-β-agarofuran Sesquiterpenes from Maytenus jelskii and Their Potential Antitumor-Promoting Effects.
abstract: Chemoprevention of human cancer appears to be a feasible strategy for cancer control, especially when chemopreventive intervention is involved during early stages of the carcinogenesis process. As a part of our ongoing research program into new chemopreventive agents, herein are reported the isolation, structural elucidation, and biological evaluation of 10 new (1-10) and three known (11-13) sesquiterpenes with a dihydro-β-agarofuran skeleton from the leaves of Maytenus jelskii Zahlbr. Their stereostructures have been elucidated by means of spectroscopic analysis, including 1D and 2D NMR techniques, ECD studies, and biogenetic considerations. The isolated metabolites and eight previously reported sesquiterpenes (14-21) were screened for their antitumor-promoting activity using a short-term in vitro assay for Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorbol-13-acetate (TPA). Six compounds from this series (4, 5, 11, and 13-15) were found to exhibit higher efficacies than β-carotene, used as reference inhibitor for EBV-EA activation. In particular, promising antitumor activity was observed for compound 5, exhibiting inhibition even at the lowest concentration assayed (10 mol ratio/TPA). Preliminary structure-activity relationship analysis revealed that the acetate, benzoate, and hydroxy groups are the most desirable substituents on the sesquiterpene scaffold for activity in the EBV-EA activation assay.
authors.affiliation: Instituto Universitario de Bio-Orgánica Antonio González, Departamento de Química Orgánica, and Instituto Canario de Investigación del Cáncer, Universidad de La Laguna , Avenida Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife, Spain.
authors.forename: Nayra R
authors.initials: NR
authors.lastname: Perestelo
authors.affiliation: Instituto Universitario de Bio-Orgánica Antonio González, Departamento de Química Orgánica, and Instituto Canario de Investigación del Cáncer, Universidad de La Laguna , Avenida Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife, Spain.
authors.forename: Ignacio A
authors.initials: IA
authors.lastname: Jiménez
authors.affiliation: Organic Chemistry in Life Science, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University , Kyoto 606-8502, Japan.
authors.forename: Harukuni
authors.initials: H
authors.lastname: Tokuda
authors.affiliation: Instituto Universitario de Bio-Orgánica Antonio González, Departamento de Química Orgánica, and Instituto Canario de Investigación del Cáncer, Universidad de La Laguna , Avenida Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife, Spain.
authors.forename: Jesús T
authors.initials: JT
authors.lastname: Vázquez
authors.affiliation: Department of Internal Medicine, International University of Health and Welfare Hospital, Nasushiobara , Tochigi 329-2763, Japan.
authors.forename: Eiichiro
authors.initials: E
authors.lastname: Ichiishi
authors.affiliation: Instituto Universitario de Bio-Orgánica Antonio González, Departamento de Química Orgánica, and Instituto Canario de Investigación del Cáncer, Universidad de La Laguna , Avenida Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife, Spain.
authors.forename: Isabel L
authors.initials: IL
authors.lastname: Bazzocchi
mesh_terms: D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D019309:Epstein-Barr Virus Nuclear Antigens / Q000187:drug effects / Q000494:pharmacology; D006801:Humans; D029755:Maytenus / Q000737:chemistry*; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010568:Peru; D018515:Plant Leaves / Q000737:chemistry; D012717:Sesquiterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology
chemical_list: D016588:Anticarcinogenic Agents; D019309:Epstein-Barr Virus Nuclear Antigens; D012717:Sesquiterpenes; D013755:Tetradecanoylphorbol Acetate