Abstract A number of novel coumarin derivatives synthesized by the reaction of 3-carbonyl chloride coumarin with some substituted aryl acid hydrazides to investigate their anti-inflammatory and anticonvulsant activities. Carrageenan (0.1 ml of 1%, w/v) was injected subplantarly in the right paw of rats to induce an acute model of inflammation. Anti-inflammatory efficacy was evaluated for 5 hours at 3 different dosages 5, 10, 25 mg/kg. After that, the changes in the level of paw edema volumes and percentage inhibition of all groups were observed and the most effective coumarin derivative was found as N'-(2-hyroxybenzoyl)-2-oxo-2H-chromene-3-carbohydrazide. In addition, N’-(2-oxo-2H-chromene-3-carbonyl)nicotinohydrazide, (E)-N’-(3-(4-hydroxyphenyl)acryloyl)-2-oxo-2H-chromene-3-carbohydrazide, and N’-(5-amino-2-hydroxybenzoyl)-2-oxo-2H-chromone-3-carbohydrazide showed their anti-inflammatory effects in a dose-dependent manner. The results of the present study, coumarin derivatives show their anti-inflammatory effects via its possible mechanism inhibiting COX. On the other hand, pentylenetetrazole (PTZ, 80 mg/kg, i.p.)-induced seizure model was used to investigate the anticonvulsant activities of six newly synthesized coumarin derivatives in mice. The onset of seizure and mortality increased, the ratio of severe grades and mortality decreased with N'-(2-hyroxybenzoyl)-2-oxo-2H-chromene-3-carbohydrazide in a dose-dependent manner (30, 100, and 300 mg/kg). Moreover, (E)-N'-cinnamoyl-2-oxo-2H-chromene-3-carbohyrazide and (E)-N'-(3-(4-hyroxyphenyl)acryloyl)-2-oxo-2H-chromene-3-carbohydrazide has potential anticonvulsant efficiency in low doses (30 mg/kg). The anticonvulsant effect of these coumarin derivatives may be through enhanced GABA-mediated inhibition in the brain.

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新型香豆素二酰肼衍生物抗炎抗惊厥活性的合成与研究

摘要 通过 3-碳酰氯香豆素与一些取代的芳基酰肼反应合成了许多新的香豆素衍生物，以研究它们的抗炎和抗惊厥活性。将角叉菜胶（0.1 ml，1%，w/v）注射到大鼠右爪足底下以诱导急性炎症模型。以 5、10、25 mg/kg 的 3 种不同剂量评估抗炎功效 5 小时。之后，观察所有组的爪水肿体积水平和抑制百分比的变化，发现最有效的香豆素衍生物为 N'-(2-羟基苯甲酰基)-2-氧代-2H-色烯-3-碳酰肼。此外，N'-(2-oxo-2H-chromene-3-carbonyl)nicotinohydrazide, (E)-N'-(3-(4-hydroxyphenyl)acryloyl)-2-oxo-2H-chromene-3-carbohydrazide , 和 N'-(5-amino-2-hydroxybenzoyl)-2-oxo-2H-chromone-3-carbohydrazide 以剂量依赖性方式显示其抗炎作用。本研究结果表明，香豆素衍生物通过其抑制 COX 的可能机制显示其抗炎作用。另一方面，戊四唑（PTZ，80 mg/kg，ip）诱导的癫痫模型用于研究六种新合成的香豆素衍生物在小鼠体内的抗惊厥活性。N'-(2-hyroxybenzoyl)-2-oxo-2H-chromene-3-carbohydrazide 以剂量依赖性方式（30、100 和 300毫克/公斤）。此外，(E)-N'-cinnamoyl-2-oxo-2H-chromene-3-carbohyrazide 和 (E)-N' -(3-(4-hyroxyphenyl)acryloyl)-2-oxo-2H-chromene-3-carbohydrazide 在低剂量 (30 mg/kg) 下具有潜在的抗惊厥作用。这些香豆素衍生物的抗惊厥作用可能是通过增强 GABA 介导的大脑抑制作用实现的。