Design, Synthesis, Anticonvulsant Evaluation, and Molecular Docking Studies of New GABA_A Agonist Derivatives.

IF 1.8 4区医学 Q3 PHARMACOLOGY & PHARMACY

Iranian Journal of Pharmaceutical Research Pub Date : 2025-03-02 eCollection Date: 2025-01-01 DOI:10.5812/ijpr-157392

Mansur Nassiri Koopaei, Parsa Moghimirad, Ebrahim Saeedian Moghadam, Nasrin Nassiri Koopaei, Massoud Amanlou, Tahmineh Akbarzadeh, Mohammad Sharifzadeh, Mohsen Amini

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引用次数: 0

Abstract

Background: The side effects and drug resistance associated with current antiepileptic drugs necessitate the design and synthesis of new candidate anticonvulsant agents.

Objectives: The present study aimed to design, synthesize, and screen a new series of gamma-aminobutyric acid (GABA) agonist derivatives for the treatment of seizures in an animal model.

Methods: The test chemical compounds were synthesized using known synthetic routes, and their structures were confirmed by various spectroscopic methods. Anticonvulsant activity was evaluated using the pentylenetetrazole (PTZ) animal model. Molecular docking studies were conducted to assess interactions with the GABA_A receptor.

Results: Some synthesized compounds significantly improved seizure symptoms and reduced mortality rates in the PTZ model. Derivative 3c demonstrated a correlation with the GABA_A receptor in the flumazenil test.

Conclusions: The synthesized molecules exhibited moderate to good activity compared to the control group. Derivative 3c notably increased seizure latency relative to the control. Flumazenil inhibitory effect tests indicated that 3c protects against PTZ-induced seizures via the synaptic GABA_A receptor.

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新型GABAA激动剂衍生物的设计、合成、抗惊厥剂评价和分子对接研究。

背景：当前抗癫痫药物的副作用和耐药性要求设计和合成新的候选抗惊厥药物。目的：本研究旨在设计、合成和筛选一系列新的γ -氨基丁酸（GABA）激动剂衍生物，用于治疗动物模型癫痫发作。方法：采用已知的合成路线合成受试化合物，并通过各种光谱方法对其结构进行确证。采用戊四唑（PTZ）动物模型评价其抗惊厥活性。进行分子对接研究以评估与GABAA受体的相互作用。结果：在PTZ模型中，一些合成化合物显著改善了癫痫发作症状，降低了死亡率。衍生物3c在氟马西尼试验中显示与GABAA受体相关。结论：与对照组相比，合成的分子具有中等至良好的活性。与对照组相比，衍生物3c显著增加了癫痫发作潜伏期。氟马西尼抑制作用实验表明，3c通过突触GABAA受体对ptz诱导的癫痫发作具有保护作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Iranian Journal of Pharmaceutical Research 医学-药学

CiteScore

3.40

自引率

6.20%

发文量

审稿时长

2 months

期刊介绍： The Iranian Journal of Pharmaceutical Research (IJPR) is a peer-reviewed multi-disciplinary pharmaceutical publication, scheduled to appear quarterly and serve as a means for scientific information exchange in the international pharmaceutical forum. Specific scientific topics of interest to the journal include, but are not limited to: pharmaceutics, industrial pharmacy, pharmacognosy, toxicology, medicinal chemistry, novel analytical methods for drug characterization, computational and modeling approaches to drug design, bio-medical experience, clinical investigation, rational drug prescribing, pharmacoeconomics, biotechnology, nanotechnology, biopharmaceutics and physical pharmacy.