1. In situ screening of 3-arylcoumarin derivatives reveals new inhibitors of mast cell degranulation.
- Author
-
de Souza Santos M, Freire de Morais Del Lama MP, Deliberto LA, da Silva Emery F, Tallarico Pupo M, and Zumstein Georgetto Naal RM
- Subjects
- Animals, Anti-Allergic Agents chemistry, Biosensing Techniques methods, Cell Line, Coumarins chemistry, High-Throughput Screening Assays, Mast Cells metabolism, Rats, Reproducibility of Results, Structure-Activity Relationship, Anti-Allergic Agents pharmacology, Cell Degranulation drug effects, Coumarins pharmacology, Mast Cells drug effects
- 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.
- Published
- 2013
- Full Text
- View/download PDF