title: Dihydro-β-agarofuran sesquiterpenes from celastraceae species as anti-tumour-promoting agents: Structure-activity relationship.
abstract: Inhibition of tumour promotion in multistage chemical carcinogenesis is considered a promising strategy for cancer chemoprevention. In an ongoing investigation of bioactive secondary metabolites from Celastraceae species, five new dihydro-β-agarofuran sesquiterpenes (1-5), named Chiapens A-E, and seventeen known ones, were isolated from Maytenus chiapensis. Their structures were elucidated by extensive NMR spectroscopic and mass spectrometric techniques, and their absolute configurations were determined by circular dichroism studies, chemical correlations and biogenic means. The isolated compounds, along with twenty known sesquiterpenes, previously isolated from Zinowiewia costaricensis, have been tested for their inhibitory effects on Epstein-Barr virus early antigen (EBV-EA) activation induced by 12-O-tetradecanoylphorpol-13-acetate (TPA). Thirty three compounds from this series showed stronger effects than that of β-carotene, the reference inhibitor. The structure-activity relationship (SAR) analysis revealed that the type of substituent, in particular at the C-1 position of the sesquiterpene scaffold, was able to modulate the anti-tumour promoting activity. Compounds 3, 6, and 33 showed significant effects in an in vivo two-stage mouse-skin carcinogenesis model.
authors: Instituto Universitario de Bio-Orgánica "Antonio González", Departamento de Química Orgánica, Universidad de La Laguna and Instituto Canario de Investigación del Cáncer, Avenida Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife, Spain; Laboratorio de Investigación en Productos Naturales, Facultad de Química y Farmacia, Universidad de El Salvador, Final Av. de Mártires y Héroes del 30 de Julio, San Salvador, El Salvador.
authors: Marvin J
authors: MJ
authors: Núñez
authors: Instituto Universitario de Bio-Orgánica "Antonio González", Departamento de Química Orgánica, Universidad de La Laguna and Instituto Canario de Investigación del Cáncer, Avenida Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife, Spain.
authors: Ignacio A
authors: IA
authors: Jiménez
authors: Instituto Universitario de Bio-Orgánica "Antonio González", Departamento de Química Orgánica, Universidad de La Laguna and Instituto Canario de Investigación del Cáncer, Avenida Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife, Spain.
authors: Cristina R
authors: CR
authors: Mendoza
authors: Instituto Universitario de Bio-Orgánica "Antonio González", Departamento de Química Orgánica, Universidad de La Laguna and Instituto Canario de Investigación del Cáncer, Avenida Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife, Spain.
authors: Marvin
authors: M
authors: Chavez-Sifontes
authors: Laboratorio de Investigación en Productos Naturales, Facultad de Química y Farmacia, Universidad de El Salvador, Final Av. de Mártires y Héroes del 30 de Julio, San Salvador, El Salvador.
authors: Morena L
authors: ML
authors: Martinez
authors: Department of Internal Medicine, International University of Health and Welfare Hospital, Nasushiobara, Tochigi 329-2763, Japan.
authors: Eiichiro
authors: E
authors: Ichiishi
authors: Hyogo College of Medicine, 1-1 Mukogawacho, Nishinomiya, Hyogo Prefecture 663-8131, Japan.
authors: Ryo
authors: R
authors: Tokuda
authors: Organic Chemistry in Life Science, Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, 606-8502, Japan.
authors: Harukuni
authors: H
authors: Tokuda
authors: Instituto Universitario de Bio-Orgánica "Antonio González", Departamento de Química Orgánica, Universidad de La Laguna and Instituto Canario de Investigación del Cáncer, Avenida Astrofísico Francisco Sánchez 2, 38206 La Laguna, Tenerife, Spain. Electronic address: ilopez@ull.es.
authors: Isabel L
authors: IL
authors: Bazzocchi
mesh_terms: D000818:Animals; D000956:Antigens, Viral / Q000378:metabolism; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D029753:Celastraceae / Q000737:chemistry*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D051379:Mice; D008813:Mice, Inbred ICR; D008958:Models, Molecular; D015394:Molecular Structure; D010212:Papilloma / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D012717:Sesquiterpenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology
chemical_list: C554292:12-O-tetradecanoylphorbol-1,3-acetate; D000956:Antigens, Viral; D000970:Antineoplastic Agents; C033305:Epstein-Barr virus early antigen; D012717:Sesquiterpenes; C079978:dihydroagarofuran; D013755:Tetradecanoylphorbol Acetate
keywords: Anti-tumour promoting agent; Dihydro-β-agarofuran sesquiterpenes; Epstein-Barr virus; Maytenus chiapensis; Structure-activity relationship; Zinowiewia costaricencis