Screening for Potential Compounds Using Drug-Repurposing of N-Methyl-D-Aspartate (NMDA) Receptor for Autism Spectrum Disorder (ASD).

IF 1.1 Q3 BIOLOGY
Tropical life sciences research Pub Date : 2025-03-01 Epub Date: 2025-03-30 DOI:10.21315/tlsr2025.36.1.12
Nordina Syamira Mahamad Shabudin, Ahmad Naqib Shuid
{"title":"Screening for Potential Compounds Using Drug-Repurposing of N-Methyl-D-Aspartate (NMDA) Receptor for Autism Spectrum Disorder (ASD).","authors":"Nordina Syamira Mahamad Shabudin, Ahmad Naqib Shuid","doi":"10.21315/tlsr2025.36.1.12","DOIUrl":null,"url":null,"abstract":"<p><p>In Malaysia, the study on autism spectrum disorders (ASD) is limited. Most studies only focus on gene neuroligin 3 (NLGN3), NLGN4X, neurexin 1 (NRXN1) and SH3. This study focuses on the N-methyl-D-aspartate (NMDA) that was believed to have a significant effect on ASD. In this study, potential compounds and drugs that can restore receptor function in autistic patients were analysed. This research used an effective in silico method known as drug-repurposing to discover and rediscover drugs and analyse the binding of potential compounds or drugs to the NMDA receptor. AMPA and DOCK4 were used as controls in this study. Using a trusted server, Drug ReposER, 13 potential compounds or drugs that bind to NMDAR were identified. Then, proceed to the docking of potential compounds or drugs that bind to the NMDA receptor using Autodock Vina, Autodock, Hdock and CB dock and three drugs were selected that have the best binding score to NMDA, AMPA and DOCK4. The drugs were alitretinoin, salicylic acid and indinavir, respectively. Next, molecular dynamics simulations were performed with all selected compounds to study drug-protein binding, with detailed analysis of bond stability using root-mean-square fluctuation (RMSF) oscillations. Finally, ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) predictions identify 4-androstenedione, tryptophan, carbocisteine and vitamin A as having minimal toxic effects. This study showed that alitretinoin, which was known to treat skin lesions from Kaposi's sarcoma, might have the ability to reverse the effect in ASD, particularly in NMDA receptors, potentially making a significant impact on the field of neurology and psychiatry.</p>","PeriodicalId":23477,"journal":{"name":"Tropical life sciences research","volume":"36 1","pages":"223-244"},"PeriodicalIF":1.1000,"publicationDate":"2025-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12189026/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Tropical life sciences research","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.21315/tlsr2025.36.1.12","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/3/30 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

In Malaysia, the study on autism spectrum disorders (ASD) is limited. Most studies only focus on gene neuroligin 3 (NLGN3), NLGN4X, neurexin 1 (NRXN1) and SH3. This study focuses on the N-methyl-D-aspartate (NMDA) that was believed to have a significant effect on ASD. In this study, potential compounds and drugs that can restore receptor function in autistic patients were analysed. This research used an effective in silico method known as drug-repurposing to discover and rediscover drugs and analyse the binding of potential compounds or drugs to the NMDA receptor. AMPA and DOCK4 were used as controls in this study. Using a trusted server, Drug ReposER, 13 potential compounds or drugs that bind to NMDAR were identified. Then, proceed to the docking of potential compounds or drugs that bind to the NMDA receptor using Autodock Vina, Autodock, Hdock and CB dock and three drugs were selected that have the best binding score to NMDA, AMPA and DOCK4. The drugs were alitretinoin, salicylic acid and indinavir, respectively. Next, molecular dynamics simulations were performed with all selected compounds to study drug-protein binding, with detailed analysis of bond stability using root-mean-square fluctuation (RMSF) oscillations. Finally, ADMET (Absorption, Distribution, Metabolism, Excretion and Toxicity) predictions identify 4-androstenedione, tryptophan, carbocisteine and vitamin A as having minimal toxic effects. This study showed that alitretinoin, which was known to treat skin lesions from Kaposi's sarcoma, might have the ability to reverse the effect in ASD, particularly in NMDA receptors, potentially making a significant impact on the field of neurology and psychiatry.

利用n -甲基- d -天冬氨酸(NMDA)受体药物再利用筛选自闭症谱系障碍(ASD)的潜在化合物
在马来西亚,对自闭症谱系障碍(ASD)的研究有限。大多数研究只关注NLGN3、NLGN4X、NRXN1和SH3基因。本研究的重点是n -甲基- d -天冬氨酸(NMDA),它被认为对ASD有显著的影响。在这项研究中,潜在的化合物和药物可以恢复自闭症患者的受体功能进行了分析。这项研究使用了一种被称为药物再利用的有效的计算机方法来发现和重新发现药物,并分析潜在化合物或药物与NMDA受体的结合。本研究以AMPA和DOCK4为对照。使用可信赖的服务器Drug ReposER,鉴定了13种与NMDAR结合的潜在化合物或药物。然后,使用Autodock对接潜在的与NMDA受体结合的化合物或药物,并选择与NMDA、AMPA和DOCK4结合评分最高的3种药物。药物分别为阿利维甲酸、水杨酸和茚地那韦。接下来,对所有选定的化合物进行分子动力学模拟以研究药物-蛋白质结合,并使用均方根波动(RMSF)振荡详细分析键的稳定性。最后,ADMET(吸收、分布、代谢、排泄和毒性)预测确定4-雄烯二酮、色氨酸、碳西氨酸和维生素A的毒性作用最小。这项研究表明,已知用于治疗卡波西肉瘤皮肤损伤的阿利维甲酸,可能有能力逆转ASD的作用,特别是对NMDA受体的作用,这可能对神经病学和精神病学领域产生重大影响。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
CiteScore
2.60
自引率
0.00%
发文量
40
审稿时长
20 weeks
期刊介绍: Tropical Life Sciences Research (TLSR) formerly known as Journal of Bioscience seeks to publish relevant ideas and knowledge addressing vital life sciences issues in the tropical region. The Journal’s scope is interdisciplinary in nature and covers any aspects related to issues on life sciences especially from the field of biochemistry, microbiology, biotechnology and animal, plant, environmental, biomedical and pharmaceutical sciences. TLSR practices double blind peer review system to ensure and maintain the good quality of articles published in this journal. Two issues are published annually in printed and electronic form. TLSR also accepts review articles, experimental papers and short communications. The Chief Editor would like to invite researchers to use this journal as a mean to rapidly promote their research findings.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:604180095
Book学术官方微信