Molecular Dynamics Simulation and Pharmacoinformatic Integrated Analysis of Bioactive Phytochemicals from Azadirachta indica (Neem) to Treat Diabetes Mellitus

Diabetes mellitus is a chronic hormonal and metabolic disorder in which our body cannot generate necessary insulin or does not act in response to it, accordingly, ensuing in discordantly high blood sugar (glucose) levels. Diabetes mellitus can lead to systemic dysfunction in the multiorgan system, i...

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Main Authors: Asif Abdullah, Partha Biswas, Md. Sahabuddin, Afiya Mubasharah, Dhrubo Ahmed Khan, Akram Hossain, Tanima Roy, Nishat Md. R. Rafi, Dipta Dey, Md. Nazmul Hasan, Shabana Bibi, Mahmoud Moustafa, Ali Shati, Hesham Hassan, Ruchika Garg
Format: Article
Language:English
Published: Wiley 2023-01-01
Series:Journal of Chemistry
Online Access:http://dx.doi.org/10.1155/2023/4170703
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author Asif Abdullah
Partha Biswas
Md. Sahabuddin
Afiya Mubasharah
Dhrubo Ahmed Khan
Akram Hossain
Tanima Roy
Nishat Md. R. Rafi
Dipta Dey
Md. Nazmul Hasan
Shabana Bibi
Mahmoud Moustafa
Ali Shati
Hesham Hassan
Ruchika Garg
author_facet Asif Abdullah
Partha Biswas
Md. Sahabuddin
Afiya Mubasharah
Dhrubo Ahmed Khan
Akram Hossain
Tanima Roy
Nishat Md. R. Rafi
Dipta Dey
Md. Nazmul Hasan
Shabana Bibi
Mahmoud Moustafa
Ali Shati
Hesham Hassan
Ruchika Garg
author_sort Asif Abdullah
collection DOAJ
description Diabetes mellitus is a chronic hormonal and metabolic disorder in which our body cannot generate necessary insulin or does not act in response to it, accordingly, ensuing in discordantly high blood sugar (glucose) levels. Diabetes mellitus can lead to systemic dysfunction in the multiorgan system, including cardiac dysfunction, severe kidney disease, lowered quality of life, and increased mortality risk from diabetic complications. To uncover possible therapeutic targets to treat diabetes mellitus, the in silico drug design technique is widely used, which connects the ligand molecules with target proteins to construct a protein-ligand network. To identify new therapeutic targets for type 2 diabetes mellitus, Azadirachta indica is subjected to phytochemical screening using in silico molecular docking, pharmacokinetic behavior analysis, and simulation-based molecular dynamic analysis. This study has analyzed around 63 phytochemical compounds, and the initial selection of the compounds was made by analyzing their pharmacokinetic properties by comparing them with Lipinski’s rule of 5. The selected compounds were subjected to molecular docking. The top four ligand compounds were reported along with the control drug nateglinide based on their highest negative molecular binding affinity. The protein-ligand interaction of selected compounds has been analyzed to understand better how compounds interact with the targeted protein structure. The results of the in silico analysis revealed that 7-Deacetyl-7-oxogedunin had the highest negative docking score of −8.9 Kcal/mol and also demonstrated standard stability in a 100 ns molecular dynamic simulation performed with insulin receptor ectodomain. It has been found that these substances may rank among the essential supplementary antidiabetic drugs for treating type 2 diabetes mellitus. It is suggested that more in vivo and in vitro research studies be carried out to support the conclusions drawn from this in silico research strategy.
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spelling doaj-art-e09eab778dce4b998ca492f34d86f5d62025-08-20T03:26:09ZengWileyJournal of Chemistry2090-90712023-01-01202310.1155/2023/4170703Molecular Dynamics Simulation and Pharmacoinformatic Integrated Analysis of Bioactive Phytochemicals from Azadirachta indica (Neem) to Treat Diabetes MellitusAsif Abdullah0Partha Biswas1Md. Sahabuddin2Afiya Mubasharah3Dhrubo Ahmed Khan4Akram Hossain5Tanima Roy6Nishat Md. R. Rafi7Dipta Dey8Md. Nazmul Hasan9Shabana Bibi10Mahmoud Moustafa11Ali Shati12Hesham Hassan13Ruchika Garg14Department of Biomedical EngineeringLaboratory of Pharmaceutical Biotechnology and BioinformaticsDepartment of Biomedical EngineeringDepartment of Biomedical EngineeringLaboratory of Pharmaceutical Biotechnology and BioinformaticsDepartment of Biomedical EngineeringMilitary Institute of Science and TechnologyDepartment of Biomedical EngineeringBiochemistry and Molecular Biology DepartmentLaboratory of Pharmaceutical Biotechnology and BioinformaticsDepartment of BioscienceDepartment of BiologyDepartment of Botany and MicrobiologyDepartment of PathologyUniversity School of Pharmaceutical SciencesDiabetes mellitus is a chronic hormonal and metabolic disorder in which our body cannot generate necessary insulin or does not act in response to it, accordingly, ensuing in discordantly high blood sugar (glucose) levels. Diabetes mellitus can lead to systemic dysfunction in the multiorgan system, including cardiac dysfunction, severe kidney disease, lowered quality of life, and increased mortality risk from diabetic complications. To uncover possible therapeutic targets to treat diabetes mellitus, the in silico drug design technique is widely used, which connects the ligand molecules with target proteins to construct a protein-ligand network. To identify new therapeutic targets for type 2 diabetes mellitus, Azadirachta indica is subjected to phytochemical screening using in silico molecular docking, pharmacokinetic behavior analysis, and simulation-based molecular dynamic analysis. This study has analyzed around 63 phytochemical compounds, and the initial selection of the compounds was made by analyzing their pharmacokinetic properties by comparing them with Lipinski’s rule of 5. The selected compounds were subjected to molecular docking. The top four ligand compounds were reported along with the control drug nateglinide based on their highest negative molecular binding affinity. The protein-ligand interaction of selected compounds has been analyzed to understand better how compounds interact with the targeted protein structure. The results of the in silico analysis revealed that 7-Deacetyl-7-oxogedunin had the highest negative docking score of −8.9 Kcal/mol and also demonstrated standard stability in a 100 ns molecular dynamic simulation performed with insulin receptor ectodomain. It has been found that these substances may rank among the essential supplementary antidiabetic drugs for treating type 2 diabetes mellitus. It is suggested that more in vivo and in vitro research studies be carried out to support the conclusions drawn from this in silico research strategy.http://dx.doi.org/10.1155/2023/4170703
spellingShingle Asif Abdullah
Partha Biswas
Md. Sahabuddin
Afiya Mubasharah
Dhrubo Ahmed Khan
Akram Hossain
Tanima Roy
Nishat Md. R. Rafi
Dipta Dey
Md. Nazmul Hasan
Shabana Bibi
Mahmoud Moustafa
Ali Shati
Hesham Hassan
Ruchika Garg
Molecular Dynamics Simulation and Pharmacoinformatic Integrated Analysis of Bioactive Phytochemicals from Azadirachta indica (Neem) to Treat Diabetes Mellitus
Journal of Chemistry
title Molecular Dynamics Simulation and Pharmacoinformatic Integrated Analysis of Bioactive Phytochemicals from Azadirachta indica (Neem) to Treat Diabetes Mellitus
title_full Molecular Dynamics Simulation and Pharmacoinformatic Integrated Analysis of Bioactive Phytochemicals from Azadirachta indica (Neem) to Treat Diabetes Mellitus
title_fullStr Molecular Dynamics Simulation and Pharmacoinformatic Integrated Analysis of Bioactive Phytochemicals from Azadirachta indica (Neem) to Treat Diabetes Mellitus
title_full_unstemmed Molecular Dynamics Simulation and Pharmacoinformatic Integrated Analysis of Bioactive Phytochemicals from Azadirachta indica (Neem) to Treat Diabetes Mellitus
title_short Molecular Dynamics Simulation and Pharmacoinformatic Integrated Analysis of Bioactive Phytochemicals from Azadirachta indica (Neem) to Treat Diabetes Mellitus
title_sort molecular dynamics simulation and pharmacoinformatic integrated analysis of bioactive phytochemicals from azadirachta indica neem to treat diabetes mellitus
url http://dx.doi.org/10.1155/2023/4170703
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