Discovery of New Symmetrical and Asymmetrical 1,4-dihydropyridine Derivatives as Potential Antihypertensive Agents: An In silico Evaluation.

IF 1.5 Q3 PERIPHERAL VASCULAR DISEASE
Ruhani Raj, Charu Parjapati, Minakshi Garg, Anupreet Kaur
{"title":"Discovery of New Symmetrical and Asymmetrical 1,4-dihydropyridine Derivatives as Potential Antihypertensive Agents: An In silico Evaluation.","authors":"Ruhani Raj, Charu Parjapati, Minakshi Garg, Anupreet Kaur","doi":"10.2174/0115734021328359241206073629","DOIUrl":null,"url":null,"abstract":"<p><strong>Introduction: </strong>Hypertension is a worldwide problem that affects people of all ethnicities and social groups. Its mortality rate has been steadily increasing. However, several pharmacological compounds have been used to manage hypertension and related issues. Calcium Channel Blockers (CCBs) based on Dihydropyridine (DHP) are used as first-line therapy. It is well established that simple adjustments to an existing medicine's fundamental structure can considerably improve its efficacy.</p><p><strong>Materials and methods: </strong>The purpose of this research study was to create potential antihypertensive drugs utilizing a 1,4-DHP scaffold and analyze their binding processes with different calcium channel proteins for comparative analysis, with PDB IDs 3LV3, 1T0J, and 6DAF. This study used molecular docking and ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) profiling to predict the binding efficacy of newly produced potential drugs, such as CCBs.</p><p><strong>Results: </strong>The binding energy of the protein with the newly created compounds ranged between -2.6 and -7.26 kcal/mol (3LV3), -7.42 to -10.36 kcal/mol (1T0J), and -6.63 to -11.98 kcal/mol (6DAF).</p><p><strong>Discussion: </strong>The predicted ADMET profiling yielded significant results, indicating that among the virtually prepared ligands, apart from the standard drugs amlodipine and nifedipine, ligand numbers 60 and 13 showed a favorable ADMET profile.</p><p><strong>Conclusion: </strong>In this study, drug development efforts focused on modifying existing hypertension medications through in silico analysis. From hundreds of synthesized ligands, 19 showed optimal docking scores. ADMET profiling of these 19 ligands revealed ligands 60 and 13 to have favorable profiles. The Swiss ADME and ADMET lab 2.0 tools confirmed these findings, highlighting their potential for further development.</p>","PeriodicalId":45941,"journal":{"name":"Current Hypertension Reviews","volume":" ","pages":""},"PeriodicalIF":1.5000,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Current Hypertension Reviews","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/0115734021328359241206073629","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"PERIPHERAL VASCULAR DISEASE","Score":null,"Total":0}
引用次数: 0

Abstract

Introduction: Hypertension is a worldwide problem that affects people of all ethnicities and social groups. Its mortality rate has been steadily increasing. However, several pharmacological compounds have been used to manage hypertension and related issues. Calcium Channel Blockers (CCBs) based on Dihydropyridine (DHP) are used as first-line therapy. It is well established that simple adjustments to an existing medicine's fundamental structure can considerably improve its efficacy.

Materials and methods: The purpose of this research study was to create potential antihypertensive drugs utilizing a 1,4-DHP scaffold and analyze their binding processes with different calcium channel proteins for comparative analysis, with PDB IDs 3LV3, 1T0J, and 6DAF. This study used molecular docking and ADMET (Absorption, Distribution, Metabolism, Excretion, Toxicity) profiling to predict the binding efficacy of newly produced potential drugs, such as CCBs.

Results: The binding energy of the protein with the newly created compounds ranged between -2.6 and -7.26 kcal/mol (3LV3), -7.42 to -10.36 kcal/mol (1T0J), and -6.63 to -11.98 kcal/mol (6DAF).

Discussion: The predicted ADMET profiling yielded significant results, indicating that among the virtually prepared ligands, apart from the standard drugs amlodipine and nifedipine, ligand numbers 60 and 13 showed a favorable ADMET profile.

Conclusion: In this study, drug development efforts focused on modifying existing hypertension medications through in silico analysis. From hundreds of synthesized ligands, 19 showed optimal docking scores. ADMET profiling of these 19 ligands revealed ligands 60 and 13 to have favorable profiles. The Swiss ADME and ADMET lab 2.0 tools confirmed these findings, highlighting their potential for further development.

发现新的对称和不对称 1,4-二氢吡啶衍生物作为潜在的抗高血压药物:一项硅学评估。
导言:高血压是一个世界性问题,影响着所有种族和社会群体的人。其死亡率一直在稳步上升。然而,已有多种药理化合物被用于控制高血压及相关问题。以二氢吡啶(DHP)为基础的钙通道阻滞剂(CCB)被用作一线疗法。众所周知,对现有药物的基本结构进行简单调整就能大大提高其疗效:本研究的目的是利用 1,4-DHP(PDB ID:3LV3、1T0J 和 6DAF)支架创建潜在的降压药物,并分析它们与不同钙通道蛋白的结合过程,以进行比较分析。该研究利用分子对接和 ADMET(吸收、分布、代谢、排泄、毒性)分析预测新生产的潜在药物(如 CCBs)的结合效力:蛋白质与新化合物的结合能介于-2.6至-7.26 kcal/mol(3LV3)、-7.42至-10.36 kcal/mol(1T0J)和-6.63至-11.98 kcal/mol(6DAF)之间:讨论:ADMET 预测分析结果表明,在实际制备的配体中,除标准药物氨氯地平和硝苯地平外,60 号和 13 号配体显示出良好的 ADMET 特征:在这项研究中,药物开发工作的重点是通过硅学分析修改现有的高血压药物。在合成的数百种配体中,19 种配体显示出最佳的对接得分。对这 19 种配体的 ADMET 分析表明,配体 60 和 13 具有良好的配体特征。瑞士 ADME 和 ADMET 实验室 2.0 工具证实了这些发现,突出了它们进一步开发的潜力。
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
Current Hypertension Reviews
Current Hypertension Reviews PERIPHERAL VASCULAR DISEASE-
CiteScore
4.80
自引率
0.00%
发文量
26
期刊介绍: Current Hypertension Reviews publishes frontier reviews/ mini-reviews, original research articles and guest edited thematic issues on all the latest advances on hypertension and its related areas e.g. nephrology, clinical care, and therapy. The journal’s aim is to publish the highest quality review articles dedicated to clinical research in the field. The journal is essential reading for all clinicians and researchers in the field of hypertension.
×
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:481959085
Book学术官方微信