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

• Type: Article in International Scientific Journal
• Date: 2011

Authors

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

Journal

Title: Journal of Medicinal Chemistry

Vol. 54

Pages: 3175-3187

ISSN: 0022-2623

Publisher: American Chemical Society

Indexing

ISI Web of Knowledge - 11 Citations

Scopus - 2 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 13