Synthesis of Tetrahydronaphthalene Lignan Esters by Intramolecular Cyclization of Ethyl p-Azidophenyl-2-phenylalkanoates and Evaluation of the Growth Inhibition of Human Tumor Cell Lines

• Tipo: Artigo em Revista Científica Internacional
• Data: 2011

Autores

Orlando Pinto (Autor) Outra; Joao Sardinha (Autor) Outra; Pedro D Vaz (Autor) Outra; Fatima Piedade (Autor) Outra; Maria J Calhorda (Autor) Outra; Rudolph Abramovitch (Autor) Outra; Nair Nazareth (Autor) Outra; Madalena Pinto (Autor) FFUP; Maria S J Nascimento (Autor) FFUP; Amelia P Rauter (Autor) Outra

Revista

Título: Journal of Medicinal Chemistry

Vol. 54

Páginas: 3175-3187

ISSN: 0022-2623

Editora: American Chemical Society

Indexação

ISI Web of Knowledge - 11 Citações

Scopus - 2 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina básica

Outras Informações

ID Authenticus: P-002-RGJ

DOI: 10.1021/jm101182s

Abstract (EN): Intramolecular cyclization via nitrenium ion of 2-phenylpentanoic/2-phenylbutanoic acid esters with a terminal p-azidophenyl group gives direct access to tetrahydronaphthalene lignan esters. The p-azidophenyl-substituted butanoate led to an ethyl spirodienone carboxylate, while its homologue pentanoate gave ethyl 4-(4-aminophenyl)-1,2,3,4-tetrahydronaphthalene-1-carboxylate in good yield. In contrast, the m-azidophenyl-substituted esters suffered aromatic nucleophilic addition of trifluoromethanesulfonate. X-ray crystallography established unequivocally the end products structure, and density functional theory studies were performed to rationalize the cyclization outcome. Reaction intermediates and end products were evaluated for their capacity to inhibit in vitro growth of the cell lines MCF-7 (breast cancer), NCI-H460 (lung cancer), SF-268 (CNS cancer), and UACC-62 (melanoma). Growth inhibition of breast, lung, and CNS cancer cell lines was observed with the spirodienone carboxylate, the m-nitrophenylalkyl iodides, and p-phenyl-substituted elongated ethyl esters, namely, the p-nitrophenylpentanoate and p-aminophenylbutanoate, with the latter being also effective on the melanoma cell line.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 13