[PMID]: | 26854381 |
[Au] Autor: | Núñez MJ; Jiménez IA; Mendoza CR; Chavez-Sifontes M; Martinez ML; Ichiishi E; Tokuda R; Tokuda H; Bazzocchi IL |
[Ad] Endereço: | 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, Fa |
[Ti] Título: | Dihydro-ß-agarofuran sesquiterpenes from celastraceae species as anti-tumour-promoting agents: Structure-activity relationship. |
[So] Source: | Eur J Med Chem;111:95-102, 2016 Mar 23. |
[Is] ISSN: | 1768-3254 |
[Cp] País de publicação: | France |
[La] Idioma: | eng |
[Ab] Resumo: | 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-ß-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 ß-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. |
[Mh] Termos MeSH primário: |
Antineoplásicos/química Antineoplásicos/farmacologia Celastraceae/química Papiloma/tratamento farmacológico Sesquiterpenos/química Sesquiterpenos/farmacologia
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[Mh] Termos MeSH secundário: |
Animais Antígenos Virais/metabolismo Antineoplásicos/síntese química Linhagem Celular Tumoral Proliferação Celular/efeitos dos fármacos Relação Dose-Resposta a Droga Ensaios de Seleção de Medicamentos Antitumorais Feminino Seres Humanos Camundongos Camundongos Endogâmicos ICR Modelos Moleculares Estrutura Molecular Papiloma/metabolismo Papiloma/patologia Sesquiterpenos/síntese química Relação Estrutura-Atividade Acetato de Tetradecanoilforbol/análogos & derivados Acetato de Tetradecanoilforbol/antagonistas & inibidores Acetato de Tetradecanoilforbol/farmacologia
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[Pt] Tipo de publicação: | JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T |
[Nm] Nome de substância:
| 0 (12-O-tetradecanoylphorbol-1,3-acetate); 0 (Antigens, Viral); 0 (Antineoplastic Agents); 0 (Epstein-Barr virus early antigen); 0 (Sesquiterpenes); 20053-66-1 (dihydroagarofuran); NI40JAQ945 (Tetradecanoylphorbol Acetate) |
[Em] Mês de entrada: | 1611 |
[Cu] Atualização por classe: | 161230 |
[Lr] Data última revisão:
| 161230 |
[Sb] Subgrupo de revista: | IM |
[Da] Data de entrada para processamento: | 160209 |
[St] Status: | MEDLINE |
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