Khokra Sukhbir L, Arora Kanika, Khan Shah A, Kaushik Pawan, Saini Reetu, Husain Asif
Institute of Pharmaceutical Sciences, Kurukshetra University, Kurukshetra-136119, Haryana, India.
Department of Pharmacy, Oman Medical College, Muscat, Sultanate of Oman.
Iran J Pharm Res. 2019 Winter;18(1):1-15.
We report herein the synthesis of ¾ substituted benzene sulfonamides linked via phenyl ring to a benzothiazole moiety. The title compounds in the two series namely -(4-(benzothiazole-2-yl) phenyl) 4- substituted benzene sulfonamides and -(4-(benzothiazole-2-yl) phenyl) 3- substituted benzene sulfonamides were synthesized by condensing 2-(3/4-aminophenyl) benzothiazole with various substituted sulfonyl chlorides. The synthesized compounds were subjected to neurotoxicity screening, computational studies, and evaluation of their anticonvulsant potential. Amongst all the synthesized compounds, compound emerged as the most potent anticonvulsant agent in maximal electroshock (MES) model (standard: phenytoin) in mice and showed three hydrogen bond interactions with the nicotinic acetylcholine ion gated receptors (PDB ID: 2BG9). Interestingly, compound showed five hydrogen bond interactions with the target protein and thus excellent binding affinity upon computational analysis but was found to be neurotoxic.
我们在此报告通过苯环连接到苯并噻唑部分的3/4-取代苯磺酰胺的合成。通过将2-(3/4-氨基苯基)苯并噻唑与各种取代的磺酰氯缩合，合成了两个系列的标题化合物，即-(4-(苯并噻唑-2-基)苯基)4-取代苯磺酰胺和-(4-(苯并噻唑-2-基)苯基)3-取代苯磺酰胺。对合成的化合物进行了神经毒性筛选、计算研究以及抗惊厥潜力评估。在所有合成的化合物中，化合物在小鼠最大电休克（MES）模型（标准：苯妥英）中表现为最有效的抗惊厥剂，并与烟碱型乙酰胆碱离子门控受体显示出三种氢键相互作用（PDB ID：2BG9）。有趣的是，化合物在计算分析中与靶蛋白显示出五种氢键相互作用，因此具有优异的结合亲和力，但被发现具有神经毒性。
