TY - JOUR
T1 - Biological Study of Naphthalene Derivatives with Antiinflammatory Activities
AU - Huang, Mei Han
AU - Wu, Sheng-Nan
AU - Wang, Jih Pyang
AU - Lin, Chen Hsing
AU - Lu, Shih I.
AU - Liao, Li Fang
AU - Shen, Ai Yu
PY - 2003/12/1
Y1 - 2003/12/1
N2 -
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.
AB -
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.
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U2 - 10.1002/ddr.10327
DO - 10.1002/ddr.10327
M3 - Article
AN - SCOPUS:0344012562
VL - 60
SP - 261
EP - 269
JO - Drug Development Research
JF - Drug Development Research
SN - 0272-4391
IS - 4
ER -