Inhibition of neutrophil O2 production by unsymmetrical methylene derivatives of benzopyrans: their use as potential antiinflammatory agents

Some unsymmetrical derivatives of benzopyrans 9 were synthesized and tested to verify their PKC inhibitory activity. For this purpose, the Mannich bases of 7-hydroxycoumarins 6 were treated with 2-(dialkylamino)benzopyran-4-ones or 3-(dialkylamino)naphtho2,1-b]pyran-1-ones 8 in the presence of acetic or propionic anhydride, yielding compounds 9. Human neutrophils stimulated with either PMA and f-MLF were used as the cellular model. The efficiency of the compounds 9 was established on their capacity to reduce the O₂⁻ production by activated human neutrophils. Compounds 9d and 9f, bearing an acetoxy group in position 7 of the chromone moiety, seem to counteract the neutrophil activation efficiently.