Amir Mohammed, Ali Israr, Hassan Mohd Zaheen, Mulakayala Naveen
Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Hamdard University, New Delhi, India.
Arch Pharm (Weinheim). 2014 Dec;347(12):958-68. doi: 10.1002/ardp.201400045. Epub 2014 Sep 24.
New hydrazone incorporated triazines were designed and synthesized using an appropriate synthetic route with regard to essential pharmacophores, and evaluated for their anticonvulsant activity through maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole-induced seizure (scPTZ) screenings. Among the tested compounds, 4-[{2-(5-(3-chlorobenzyl)-3-phenyl-1,2,4-triazine-6-yl)hydrazono}methyl]-N,N-dimethylaniline 6k (MES ED50 54.31, scPTZ ED50 92.01) and 4-[{2-(5-(4-chlorobenzyl)-3-phenyl-1,2,4-triazine-6-yl)hydrazono}methyl]-N,N-dimethylaniline 6r (MES ED50 46.05, scPTZ ED50 83.90) emerged as the most active anticonvulsant agents having GABAergic effects. Compounds 6k and 6r also showed lesser CNS depressant effect than the standard drug carbamazepine. To obtain further insights into the binding interactions of these molecules, molecular docking studies were carried out.
设计并合成了新型含腙三嗪，采用合适的合成路线引入关键药效基团，并通过最大电休克惊厥（MES）和皮下注射戊四氮诱导惊厥（scPTZ）筛选评估其抗惊厥活性。在所测试的化合物中，4 - [{2 - (5 - (3 - 氯苄基)-3 - 苯基 - 1,2,4 - 三嗪 - 6 - 基)腙基}甲基]-N,N - 二甲基苯胺6k（MES ED50 54.31，scPTZ ED50 92.01）和4 - [{2 - (5 - (4 - 氯苄基)-3 - 苯基 - 1,2,4 - 三嗪 - 6 - 基)腙基}甲基]-N,N - 二甲基苯胺6r（MES ED50 46.05，scPTZ ED50 83.90）成为具有GABA能效应的最具活性的抗惊厥剂。化合物6k和6r与标准药物卡马西平相比，还表现出较小的中枢神经系统抑制作用。为了进一步深入了解这些分子的结合相互作用，进行了分子对接研究。
