Aggarwal Navneet, Mishra Pradeep
Department of Pharmaceutical Chemistry, Hindu College of Pharmacy, Sonepat, Haryana, India.
J Pharm Pharm Sci. 2004 Aug 11;7(2):260-4.
A series of 4-aryl substituted semicarbazones of citral and R- (-) carvone were designed and synthesized to meet the structural requirements essential for anticonvulsant activity.
TLC evaluated purity of synthesized compounds and their structure confirmed by infrared spectroscopy, proton magnetic resonance spectroscopy and by nitrogen estimation. All the compounds were evaluated for anticonvulsant activity by maximal electroshock (MES) and subcutaneous metrazol (ScMet) induced seizure methods and minimal motor impairment was determined by rotorod test.
All the synthesized compounds exhibited significant protection after intraperitoneal (i.p.) administration in MES. Seventy two percent of the compounds exhibited protection in ScMet test. Some of them also showed good activity after oral administration. The results showed that anticonvulsants with cyclic and acyclic terpenoid moiety retain activity in MES as well as ScMet test. The p-fluoro aryl substituted semicarbazones emerged as the most active analogue in both cyclic and acyclic terpenes.
Semicarbazones with terpenoid as the lipophilic moiety resulted in compounds with broad spectrum of anticonvulsant activity and therefore, they may be utilized for the future development of novel anticonvulsants with broad spectrum of anticonvulsant activity. The results also validated pharmacophore model with four binding sites essential for anticonvulsant activity.
设计并合成了一系列柠檬醛和R-（-）香芹酮的4-芳基取代氨基脲，以满足抗惊厥活性所必需的结构要求。
通过薄层色谱法评估合成化合物的纯度，并通过红外光谱、质子磁共振光谱和氮含量测定来确认其结构。所有化合物均通过最大电休克（MES）和皮下注射戊四氮（ScMet）诱导惊厥法评估抗惊厥活性，并通过转棒试验确定最小运动损伤。
所有合成化合物在腹腔注射（i.p.）MES后均表现出显著的保护作用。72%的化合物在ScMet试验中表现出保护作用。其中一些化合物口服后也显示出良好的活性。结果表明，具有环状和非环状萜类部分的抗惊厥药在MES和ScMet试验中均保持活性。对氟芳基取代氨基脲在环状和非环状萜类中均成为最具活性的类似物。
以萜类为亲脂性部分的氨基脲产生了具有广谱抗惊厥活性的化合物，因此，它们可用于未来开发具有广谱抗惊厥活性的新型抗惊厥药。结果还验证了具有抗惊厥活性所必需的四个结合位点的药效团模型。
