N,N-dialkylaminosubstituted chromones and isoxazoles as potential anti-inflammatory agents

The ability of some N,N-dialkylaminosubstituted chromones and isoxazoles to inhibit the protein kinase C (PKC) dependent signal transduction pathway was tested. As a cellular model, human neutrophils stimulated with either phorbol myristate acetate (PMA) or formylmethionine-leucine-phenylalanine (f-MLF) were used. The efficiency of the compounds was established by their capacity to reduce the O2- production by activated human neutrophils. Compounds carrying a 3-bis(2-methoxyethyl)amino group, a substituent found active in previously tested tricyclic compounds, do not show significant anti-PKC activity in this study. On the other hand, substitution with a 1-piperidinyl group leads all tested compounds to a high biological activity against stimulated neutrophils.