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含1,3,4-恶二唑部分的苯并噻唑类新型抗癫痫药物的设计、合成与评价

Design, Synthesis, , and Evaluation of Benzothiazoles Bearing a 1,3,4-Oxadiazole Moiety as New Antiepileptic Agents.

作者信息

Chauhan Bharti, Kumar Rajnish, Singh Himanshu, Afzal Obaid, Altamimi Abdulmalik Saleh Alfawaz, Abdullah Mohd Mustaqeem, Yar Mohammad Shahar, Ahsan Mohamed Jawed, Kumar Neeraj, Yadav Sanjay Kumar

机构信息

Noida Institute of Engineering and Technology (Pharmacy Institute), Greater Noida 201306, India.

Department of Pharmaceutical Chemistry, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj 11942, Saudi Arabia.

出版信息

ACS Omega. 2023 Jan 5;8(2):2520-2530. doi: 10.1021/acsomega.2c06967. eCollection 2023 Jan 17.

Abstract

In the presented manuscript, a new series of 2-[4-methoxy-3-(5-substituted phenyl-[1,3,4]oxadiazol-2-ylmethoxy)-phenyl]-benzothiazoles () have been synthesized and studied and for their anticonvulsant potential. Maximum electroshocks (MES) and subcutaneous pentylenetetrazol (scPTZ) models have been used for anticonvulsant activity. Auto Dock 4.2 software was used for studies, and the targeted protein was 5IOV.sThe antidepressant activity of selected compounds (most active) was determined as a reduction in locomotor activity through an actophotometer. and studies proved that among all the synthesized compounds, and were the most potent with no neurotoxicity as compared to conventional drugs (phenytoin and phenobarbital). The studies also indicated about different binding interactions of synthetic compounds to localize the binding receptors. The most likely mode of action for these drugs, according to the docking analysis of active compounds with various targets, is their binding to the VGCC and NMDA receptors.

摘要

在本论文中,已合成了一系列新的2-[4-甲氧基-3-(5-取代苯基-[1,3,4]恶二唑-2-基甲氧基)-苯基]-苯并噻唑,并对其抗惊厥潜力进行了研究。最大电休克(MES)和皮下注射戊四氮(scPTZ)模型用于抗惊厥活性研究。使用Auto Dock 4.2软件进行研究,目标蛋白为5IOV。通过活动光度计测定所选化合物(活性最高)的抗抑郁活性,即运动活性的降低。研究证明,在所有合成化合物中,与传统药物(苯妥英和苯巴比妥)相比,[具体化合物]和[具体化合物]最有效且无神经毒性。[相关研究]还表明了合成化合物与结合受体定位的不同结合相互作用。根据活性化合物与各种靶点的对接分析,这些药物最可能的作用方式是它们与电压门控钙通道(VGCC)和N-甲基-D-天冬氨酸(NMDA)受体结合。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7396/9851031/f8e64325c370/ao2c06967_0002.jpg

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