title: In situ screening of 3-arylcoumarin derivatives reveals new inhibitors of mast cell degranulation.
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.
authors.affiliation: 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.
authors.forename: Marcela
authors.initials: M
authors.lastname: de Souza Santos
authors.forename: Maria Perpétua
authors.initials: MP
authors.lastname: Freire de Morais Del Lama
authors.forename: Laila Aparecida
authors.initials: LA
authors.lastname: Deliberto
authors.forename: Flávio
authors.initials: F
authors.lastname: da Silva Emery
authors.forename: Mônica
authors.initials: M
authors.lastname: Tallarico Pupo
authors.forename: Rose Mary
authors.initials: RM
authors.lastname: Zumstein Georgetto Naal
mesh_terms: D000818:Animals; D018926:Anti-Allergic Agents / Q000737:chemistry / Q000494:pharmacology*; D015374:Biosensing Techniques / Q000379:methods; D015550:Cell Degranulation / Q000187:drug effects*; D002460:Cell Line; D003374:Coumarins / Q000737:chemistry / Q000494:pharmacology*; D057166:High-Throughput Screening Assays; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D015203:Reproducibility of Results; D013329:Structure-Activity Relationship
chemical_list: D018926:Anti-Allergic Agents; D003374:Coumarins