{"title":"Virtual screening and molecular dynamics of anti-Alzheimer compounds from <i>Cardiospermum halicacabum</i> via GC-MS.","authors":"Selvan Kaviyarasu, Nallamuthu Padmanaban, Sulekha Khute, Gokhan Zengin, Paranthaman Subash","doi":"10.3389/fchem.2025.1586728","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>Ayurveda is an ancient Indian medicinal system that uses medicinal plants for their neuroprotective effects. Ayurveda claims that the (<i>C. halicacabum</i>) leaves possess significant neuroprotective properties. Alzheimer's is characterized by the accumulation of amyloid-β, acetylcholinesterase, and tau tangles that interfere with neural transmission and impair cognitive abilities.</p><p><strong>Objectives: </strong>This study aimed to identify novel potential anti-Alzheimer phytoconstituents of <i>C. halicacabum</i> leaves using <i>in silico</i> methods.</p><p><strong>Methods: </strong>This study utilized the Box-Behnken design within the response surface methodology (RSM) to optimize and combine the effects of process variables, namely powder weight, solvent volume, and extraction time, on the microwave-assisted extraction (MAE) <i>of C. halicacabum</i> leaves. The optimization process revealed that these variables, along with microwave usage, significantly influenced the extraction yield. The ethanolic extract was examined using gas chromatography-mass spectrometry (GC-MS) analysis, and the identified phytoconstituents were further analyzed through computer-based simulations, including docking, absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies, assessment of drug-likeness, molecular dynamics, LigPlot analysis, and density functional theory (DFT) analysis.</p><p><strong>Results: </strong>Gas chromatography-mass spectrometry (GC-MS) analysis identified 40 phytoconstituents and 37 were successfully characterized. Molecular docking and dynamics simulations revealed two lead compounds, acetic acid (dodecahydro-7-hydroxy-1,4b,8,8-tetramethyl-10-oxo-2(1H)-phenanthrenylidene)-,2-(dimethylamino)ethyl ester, [1R-(1. alpha)], and 1-(2-hydroxyethoxy)-2-methyldodecane, which exhibited superior stability in the docked complex compared to galantamine.</p><p><strong>Conclusion: </strong>Based on computational predictions and observed pharmacological properties, these findings suggest that phytoconstituents may have therapeutic effects against selected AD targets.</p>","PeriodicalId":12421,"journal":{"name":"Frontiers in Chemistry","volume":"13 ","pages":"1586728"},"PeriodicalIF":3.8000,"publicationDate":"2025-04-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12006154/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Frontiers in Chemistry","FirstCategoryId":"92","ListUrlMain":"https://doi.org/10.3389/fchem.2025.1586728","RegionNum":3,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2025/1/1 0:00:00","PubModel":"eCollection","JCR":"Q2","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
Background: Ayurveda is an ancient Indian medicinal system that uses medicinal plants for their neuroprotective effects. Ayurveda claims that the (C. halicacabum) leaves possess significant neuroprotective properties. Alzheimer's is characterized by the accumulation of amyloid-β, acetylcholinesterase, and tau tangles that interfere with neural transmission and impair cognitive abilities.
Objectives: This study aimed to identify novel potential anti-Alzheimer phytoconstituents of C. halicacabum leaves using in silico methods.
Methods: This study utilized the Box-Behnken design within the response surface methodology (RSM) to optimize and combine the effects of process variables, namely powder weight, solvent volume, and extraction time, on the microwave-assisted extraction (MAE) of C. halicacabum leaves. The optimization process revealed that these variables, along with microwave usage, significantly influenced the extraction yield. The ethanolic extract was examined using gas chromatography-mass spectrometry (GC-MS) analysis, and the identified phytoconstituents were further analyzed through computer-based simulations, including docking, absorption, distribution, metabolism, excretion, and toxicity (ADMET) studies, assessment of drug-likeness, molecular dynamics, LigPlot analysis, and density functional theory (DFT) analysis.
Results: Gas chromatography-mass spectrometry (GC-MS) analysis identified 40 phytoconstituents and 37 were successfully characterized. Molecular docking and dynamics simulations revealed two lead compounds, acetic acid (dodecahydro-7-hydroxy-1,4b,8,8-tetramethyl-10-oxo-2(1H)-phenanthrenylidene)-,2-(dimethylamino)ethyl ester, [1R-(1. alpha)], and 1-(2-hydroxyethoxy)-2-methyldodecane, which exhibited superior stability in the docked complex compared to galantamine.
Conclusion: Based on computational predictions and observed pharmacological properties, these findings suggest that phytoconstituents may have therapeutic effects against selected AD targets.
期刊介绍：
Frontiers in Chemistry is a high visiblity and quality journal, publishing rigorously peer-reviewed research across the chemical sciences. Field Chief Editor Steve Suib at the University of Connecticut is supported by an outstanding Editorial Board of international researchers. This multidisciplinary open-access journal is at the forefront of disseminating and communicating scientific knowledge and impactful discoveries to academics, industry leaders and the public worldwide.
Chemistry is a branch of science that is linked to all other main fields of research. The omnipresence of Chemistry is apparent in our everyday lives from the electronic devices that we all use to communicate, to foods we eat, to our health and well-being, to the different forms of energy that we use. While there are many subtopics and specialties of Chemistry, the fundamental link in all these areas is how atoms, ions, and molecules come together and come apart in what some have come to call the “dance of life”.
All specialty sections of Frontiers in Chemistry are open-access with the goal of publishing outstanding research publications, review articles, commentaries, and ideas about various aspects of Chemistry. The past forms of publication often have specific subdisciplines, most commonly of analytical, inorganic, organic and physical chemistries, but these days those lines and boxes are quite blurry and the silos of those disciplines appear to be eroding. Chemistry is important to both fundamental and applied areas of research and manufacturing, and indeed the outlines of academic versus industrial research are also often artificial. Collaborative research across all specialty areas of Chemistry is highly encouraged and supported as we move forward. These are exciting times and the field of Chemistry is an important and significant contributor to our collective knowledge.
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