Noida Institute of Engineering and Technology, Pharmacy Institute), Greater Noida, 201310, India.
School of Pharmacy, Graphic Era Hill University, 248002, Dehradun, India.
Chem Biodivers. 2024 Aug;21(8):e202400642. doi: 10.1002/cbdv.202400642. Epub 2024 Jul 14.
New 2-(4-benzothiazol-2-yl-phenoxy)-1-(3,5-diphenyl-4,5-dihydro-pyrazol-1-yl)-ethanones (9a-o) have been designed and synthesized. All the synthesized compounds were characterized by thin layer chromatography and spectral analysis. The antiepileptic potential of the synthesized compounds has been tested by following standard animal screening models, including maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) models. The neurotoxic and antidepression effects of the synthesized compounds were checked by utilizing rotarod apparatus, and motor impairment test (by actophotometer) respectively. The study concluded that compounds 9c, 9d, 9f, 9i, 9n, and 9o possessed good antiepileptic potential compared to standard drugs like carbamazepine and phenytoin. The results of the rotarod performance test also established them without any neurotoxicity. The motor impairment test revealed that the synthesized compounds are also good antidepressants. In-silico studies have been performed for calculation of pharmacophore pattern, prediction of pharmacokinetic properties which determine the eligibility of synthesized compounds as orally administered molecules and interactions with the target proteins. The result of in-silico studies reinforced results obtained by in vivo study of the synthesized compounds and their possible mechanism of antiepileptic action i. e. via inhibiting voltage-gated sodium channels (VGSCs) and gamma-aminobutyric acid-A receptor.
新的 2-(4-苯并噻唑-2-基-苯氧基)-1-(3,5-二苯基-4,5-二氢-吡唑-1-基)-乙酮（9a-o）已被设计和合成。所有合成的化合物都通过薄层色谱和光谱分析进行了表征。通过以下标准动物筛选模型测试了合成化合物的抗癫痫潜力，包括最大电休克（MES）和皮下戊四氮（scPTZ）模型。通过旋转棒装置和运动障碍测试（通过行为光度计）分别检查了合成化合物的神经毒性和抗抑郁作用。研究得出结论，与卡马西平、苯妥英等标准药物相比，化合物 9c、9d、9f、9i、9n 和 9o 具有良好的抗癫痫潜力。旋转棒性能测试的结果也表明它们没有任何神经毒性。运动障碍测试表明，合成化合物也是良好的抗抑郁药。进行了计算药效团模式、预测药代动力学特性的计算机辅助研究，这些特性决定了合成化合物作为口服分子的合格性，并与靶蛋白相互作用。计算机辅助研究的结果加强了对合成化合物的体内研究结果，以及它们可能的抗癫痫作用机制，即通过抑制电压门控钠离子通道（VGSCs）和γ-氨基丁酸-A 受体。
