Effects of 4-piperidinomethyl-2-isopropyl-5-methylphenol on oxidative stress and calcium current.
4-Piperidinomethyl-2-isopropyl-5-methylphenol (THPI) was synthesized by reaction of thymol with piperidine and formaldehyde. The biological effect of THPI on superoxide anion scavenging activity, antiplatelet activity and calcium current inhibition were investigated. THPI (50 microM) was shown to be a scavenger of superoxide radicals in human neutrophils stimulated with N-formyl-Met-Leu-Phe (66% inhibition). Since superoxide anions are essential for platelet aggregation and L-type Ca2+-channel activity, we further found that THPI inhibited platelet aggregation induced by arachidonic acid (IC50 46.80+/-6.88 microM). The effect of THPI on Ca2+ current in NG108-15 cells was investigated using the whole-cell voltage-clamp technique. THPI inhibited voltage-dependent L-type Ca2+ current (ICa, L). The IC50 value of THPI-induced inhibition of ICa, L was 3.60+/-0.81 microM. THPI caused no change in the overall shape of the current-voltage relationship of ICa, L. This indicates that THPI is an inhibitor of ICa, L in NG108-15 cells. Therefore, the channel-blocking properties of THPI may contribute to the underlying mechanism by which it affects neuronal or neuroendocrine function. Furthermore, no significant cytotoxic effects of THPI (0.3-50 microM) were observed in NG108-15 cells. The results indicate that THPI is a potential reactive oxygen species scavenger and may prevent platelet aggregation or inhibit L-type Ca2+-channel activity, possibly by scavenging reactive oxygen species.
Huang
Mei-Han
MH
Department of Medical Technology, Fooyin University, Ta-Liao, Kaohsiung County, Taiwan.
Liao
Li-Fang
LF
Kuo
Shih-Hsien
SH
Chen
Chi-Lan
CL
Shen
Ai-Yu
AY
D000200:Action Potentials / Q000187:drug effects; D000328:Adult; D000818:Animals; D000975:Antioxidants / Q000138:chemical synthesis / Q000494:pharmacology; D016718:Arachidonic Acid / Q000009:adverse effects; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D016166:Free Radical Scavengers / Q000378:metabolism; D006801:Humans; D051379:Mice; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects* / Q000502:physiology; D010636:Phenols / Q000138:chemical synthesis / Q000494:pharmacology*; D010880:Piperidines / Q000138:chemical synthesis / Q000494:pharmacology*; D010974:Platelet Aggregation / Q000187:drug effects / Q000502:physiology; D013481:Superoxides / Q000037:antagonists & inhibitors / Q000378:metabolism
C506851:4-piperidinomethyl-2-isopropyl-5-methylphenol; D000975:Antioxidants; D020746:Calcium Channels, L-Type; D016166:Free Radical Scavengers; D010636:Phenols; D010880:Piperidines; D013481:Superoxides; D016718:Arachidonic Acid