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布赫-哈姆化合物抗抑郁和细胞毒性活性的生物学评价、密度泛函理论计算及分子对接研究

Biological Evaluation, DFT Calculations and Molecular Docking Studies on the Antidepressant and Cytotoxicity Activities of Buch.-Ham. Compounds.

作者信息

Rahman Jinnat, Tareq Abu Montakim, Hossain Md Mohotasin, Sakib Shahenur Alam, Islam Mohammad Nazmul, Ali Md Hazrat, Uddin A B M Neshar, Hoque Muminul, Nasrin Mst Samima, Emran Talha Bin, Capasso Raffaele, Reza A S M Ali, Simal-Gandara Jesus

机构信息

Department of Pharmacy, International Islamic University Chittagong, Kumira, Chittagong 4318, Bangladesh.

Department of Theoretical and Computational Chemistry, University of Dhaka, Dhaka 1000, Bangladesh.

出版信息

Pharmaceuticals (Basel). 2020 Sep 3;13(9):232. doi: 10.3390/ph13090232.

DOI:10.3390/ph13090232
PMID:32899148
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7557754/
Abstract

Buch.-Ham. is commonly used in folk medicine against various disorders. The present study investigated the antidepressant and cytotoxicity activity of methanol extract of (MECP) along with quantitative phytochemical analysis by GC-MS method. Here, the GC-MS study of MECP presented 41 compounds, among which most were fatty acids, esters, terpenoids and oximes. The antidepressant activity was assessed by the forced swimming test (FST) and tail suspension test (TST) models. In contrast, MECP (200 and 400 mg/kg) exhibited a significant and dose-dependent manner reduction in immobility comparable with fluoxetine (10 mg/kg) and phenelzine (20 mg/kg). MECP showed a weak toxicity level in the brine shrimp lethality bioassay (ED: 358.65 µg/mL) comparable to the standard drug vincristine sulfate (ED: 2.39 µg/mL). Three compounds from the GC-MS study were subjected to density functional theory (DFT) calculations, where only cyclopentadecanone oxime showed positive and negative active binding sites. Cyclopentadecanone oxime also showed a good binding interaction in suppressing depression disorders by blocking monoamine oxidase and serotonin receptors with better pharmacokinetic and toxicological properties. Overall, the MECP exhibited a significant antidepressant activity with moderate toxicity, which required further advance studies to identify the mechanism.

摘要

布赫-哈姆通常用于民间医学治疗各种疾病。本研究通过气相色谱-质谱联用(GC-MS)方法,对[植物名称未给出]甲醇提取物(MECP)的抗抑郁和细胞毒性活性进行了研究,并进行了定量植物化学分析。在此,MECP的GC-MS研究显示有41种化合物,其中大多数是脂肪酸、酯类、萜类和肟类。通过强迫游泳试验(FST)和悬尾试验(TST)模型评估抗抑郁活性。相比之下,MECP(200和400毫克/千克)与氟西汀(10毫克/千克)和苯乙肼(20毫克/千克)相比,在不动时间上呈现出显著的剂量依赖性降低。MECP在卤虫致死生物测定中显示出较弱的毒性水平(半数致死剂量:358.65微克/毫升),与标准药物硫酸长春新碱(半数致死剂量:2.39微克/毫升)相当。GC-MS研究中的三种化合物进行了密度泛函理论(DFT)计算,其中只有环十五烷酮肟显示出正负活性结合位点。环十五烷酮肟通过阻断单胺氧化酶和血清素受体,在抑制抑郁症方面也显示出良好的结合相互作用,具有更好的药代动力学和毒理学特性。总体而言,MECP表现出显著的抗抑郁活性且毒性适中,这需要进一步深入研究以确定其作用机制。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/976c/7557754/07f75f55d416/pharmaceuticals-13-00232-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/976c/7557754/07f75f55d416/pharmaceuticals-13-00232-g005.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/976c/7557754/07f75f55d416/pharmaceuticals-13-00232-g005.jpg

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