Cited by 28Plant-derived Lignans Synthesis and BioactivitySynthesis and biological activityChemical Reactions and Mechanisms

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

Pinto, Orlando, Sardinha, João, Vaz, Pedro D., Piedade, Fátima, Calhorda, Maria J., Abramovitch, Rudolph, Nazareth, Nair, Pinto, Madalena +2 more·2011·Journal of Medicinal Chemistry

Abstract

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.

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Crossref · 10.1021/jm101182s

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Authors
Pinto, O., Sardinha, J., Vaz, P. D., Piedade, F., Calhorda, M. J., Abramovitch, R., Nazareth, N., Pinto, M., Nascimento, M. S. J., & Rauter, A. P.
Affiliations
  • University of Lisbon (PT)
  • Universidade de Lisboa, Faculdade de Ciências, Centro de Química e Bioquímica/Departamento de Química e Bioquímica (CQB/DQB), Ed. C8, Piso 5, 1749-016 Lisboa, Portugal
  • Clemson University (US)
  • Centro de Estudos de Química Medicinal da Universidade do Porto (CEQUIMED-UP), Departamento de Ciências Químicas, Laboratório de Química Orgânica e Farmacêutica, Faculdade de Farmácia, Universidade do Porto, Rua Aníbal Cunha 164, 4050-047 Porto, Portugal
  • Universidade do Porto (PT)
Corresponding author
Rauter, Amélia P.
Venue
Journal of Medicinal Chemistry
Published
2011-04-19
Volume
54
Issue
9
Pages
3175-3187
ISSN
  • 0022-2623 (ISSN-L)
  • 1520-4804
OpenAlex
W2323646647
Cited by
27
References
73
Citations by year
2024: 6 · 2023: 1 · 2022: 4 · 2021: 2 · 2020: 1 · 2019: 1 · 2018: 1 · 2017: 5 · 2016: 2 · 2015: 2 · 2013: 2
FWCI
0.26
Type
journal article
Language
en
Open access
closed
Locations
  • Journal of Medicinal Chemistry (publishedVersion)
  • PubMed (publishedVersion)
  • Science and Technology Facilities Council (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant-derived Lignans Synthesis and Bioactivity
  • Physical Sciences › Chemistry › Organic Chemistry › Synthesis and biological activity
  • Physical Sciences › Chemistry › Physical and Theoretical Chemistry › Chemical Reactions and Mechanisms
Keywords
intramolecular cyclization, nitrenium ions, structure-activity relationship, antiproliferative activity, MCF-7 cells, NCI-H460 lung cancer cells
MeSH terms
Antineoplastic Agents, Azides, Cyclization, Drug Screening Assays, Antitumor, Esters, Humans, Models, Molecular, Spiro Compounds, Structure-Activity Relationship, Tetrahydronaphthalenes, Lignans, Crystallography, X-Ray, Cell Line, Tumor, Cell Proliferation

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