In this study, 18 synthetic naphthalene derivatives were tested for their inhibitory effects on the activation of neutrophils stimulated with N-formyl-methionyl-leucyl-phenylalanine (fMLP) or phorbol myristic acetate (PMA). Some of these compounds showed significant antiinflammatory activities. In general, esterification of 1-naphthalene to compound 14 (2-hydroxymethyl-1-naphthol diacetate; TAC) enhanced the antioxidant activity. Compound 15, N,N-bis(2-hydroxy-1-naphthylmethyl) amine, has moderate inhibitory activity on neutrophils stimulated with fMLP as compared to Mannich bases of naphthylene derivatives. Either substitution at 1 or 2 position, except TAC, disfavored the inhibitory effects evoked by PMA stimulation. The influence of these compounds on the release of granule enzyme lysozyme-induced by fMLP was measured. TAC had the highest potency on the inhibition of lysozyme release from rat neutrophil degranulation. The effects of TAC on ionic currents in a mouse neuroblastoma and rat glioma hybrid cell line, NG105-18, were also investigated with the aid of the whole-cell patch-clamp technique. TAC caused an inhibitory effect on voltage-dependent L-type Ca 2+ current (I Ca,L ) with an IC 50 value of 0.8 μM. The inhibitory effect of TAC on I Ca,L may not be caused by its inhibition of superoxide formation. Such an effect may, also in part, affect neuronal function.
All Science Journal Classification (ASJC) codes
- Drug Discovery