Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and Research, Jamia Hamdard University, New Delhi, India.
School of Chemical Science, University of Sains Penang, Penang, Malaysia.
Arch Pharm (Weinheim). 2017 Oct;350(10). doi: 10.1002/ardp.201700135. Epub 2017 Sep 1.
A series of new hybrid benzimidazole containing pyridazinones derivatives were designed and synthesized in accordance with the pharmacophoric requirements essential for the anticonvulsant activity. The synthesized compounds were evaluated for anticonvulsant activity on mice by the gold standard maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ)-induced seizure models. Among the compounds tested, SS-4F showed significant anticonvulsant activity in both the screens with ED values of 25.10 and 85.33 mg/kg in the MES and scPTZ screens, respectively. Compound SS-4F emerged as safer and effective anticonvulsant due to its several-fold higher protective indices. Further, the gamma-aminobutyric acid (GABA) estimation result showed a marked increase in the GABA level (1.7-fold) as compared to the control, which was further confirmed by good binding properties with the GABA receptor.
根据抗惊厥活性所必需的药效团要求，设计并合成了一系列新型含苯并咪唑的哒嗪酮类杂合化合物。通过最大电休克（MES）和皮下戊四氮（scPTZ）诱导的惊厥模型，用标准金方法评估合成化合物对小鼠的抗惊厥活性。在所测试的化合物中，SS-4F 在两种筛选中均表现出显著的抗惊厥活性，在 MES 和 scPTZ 筛选中的 ED 值分别为 25.10 和 85.33mg/kg。由于其保护指数高出数倍，化合物 SS-4F 是一种更安全有效的抗惊厥药物。此外，GABA 测定结果显示 GABA 水平显著升高（1.7 倍），与对照组相比，这进一步通过与 GABA 受体的良好结合特性得到证实。
