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In situ screening of 3-arylcoumarin derivatives reveals new inhibitors of mast cell degranulation

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Abstract

Due to the severity and high prevalence of allergic diseases, there is growing interest in the development of inhibitors of such conditions. 3-Arylcoumarin derivatives emerge as promising compounds for the treatment of allergic disorders, in particular due to their close structural similarity to flavonoids, whose anti-allergic activity has been extensively reported. The aim of this work was to perform a screening of a set of 3-arylcoumarins as potential inhibitors of mast cell degranulation, a key event for the development of allergic reactions. For that purpose, it was utilized a biosensor model based on mast cells, whose in vitro assay allows for such screening, in a high throughput fashion, and also permits bringing to attention some coumarin structural features that are important for their biological activity. The mast cell-based biosensor was shown to discriminate, with high sensitivity and reproducibility, between coumarins that did not affect or caused different degrees of inhibition of degranulation. Among active coumarins, some substituents could be accounted for their inhibitory activity, such as the hydroxylation of positions 6 and 2′ of 3-phenylcoumarins, in addition to catechol, amino and thiophene moieties. In summary, 3-arylcoumarins could be suggested as potential candidates for the development of new anti-allergic drugs.

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Acknowledgments

The authors thank Drs. Barbara Baird and David Holowka (Cornell University) for the kind gifts: DNP-BSA and anti-DNP IgE. This work was supported by Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES), grant # 1277/10-3, Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP), grant # 2008/01712-6 and Instituto Nacional de Ciência e Tecnologia de Bioanalítica. MTP also thanks Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) for grant fellowship.

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The authors declare they have no conflict of interest.

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Authors and Affiliations

  1. Departamento de Física e Química, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Avenida do Café, s/n-Campus Universitário, Ribeirão Preto, SP, 14040-903, Brazil

    Marcela de Souza Santos, Maria Perpétua Freire de Morais Del Lama, Laila Aparecida Deliberto & Rose Mary Zumstein Georgetto Naal

  2. Instituto de Ciência e Tecnologia de Bioanalítica, Campinas, Brazil

    Marcela de Souza Santos, Maria Perpétua Freire de Morais Del Lama, Laila Aparecida Deliberto & Rose Mary Zumstein Georgetto Naal

  3. Departamento de Ciências Farmacêuticas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, Brazil

    Flávio da Silva Emery & Mônica Tallarico Pupo

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  1. Marcela de Souza Santos
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  2. Maria Perpétua Freire de Morais Del Lama
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  6. Rose Mary Zumstein Georgetto Naal
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Correspondence to Rose Mary Zumstein Georgetto Naal.

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de Souza Santos, M., Freire de Morais Del Lama, M.P., Deliberto, L.A. et al. In situ screening of 3-arylcoumarin derivatives reveals new inhibitors of mast cell degranulation. Arch. Pharm. Res. 36, 731–738 (2013). https://doi.org/10.1007/s12272-013-0084-8

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