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In Silico Molecular Docking Analysis of Karanjin against Alzheimer's and Parkinson's Diseases as a Potential Natural Lead Molecule for New Drug Design, Development and Therapy.
Molecules. 2022 Apr 29; 27(9)M

Abstract

Parkinson's disease (PD) and Alzheimer's disease (AD) are neurodegenerative disorders that have emerged as among the serious health problems of the 21st century. The medications currently available to treat AD and PD have limited efficacy and are associated with side effects. Natural products are one of the most vital and conservative sources of medicines for treating neurological problems. Karanjin is a furanoflavonoid, isolated mainly from Pongamia pinnata with several medicinal plants, and has been reported for numerous health benefits. However, the effect of karanjin on AD and PD has not yet been systematically investigated. To evaluate the neuroprotective effect of karanjin, extensive in silico studies starting with molecular docking against five putative targets for AD and four targets for PD were conducted. The findings were compared with three standard drugs using Auto Dock 4.1 and Molegro Virtual Docker software. Additionally, the physiochemical properties (Lipinski rule of five), drug-likeness and parameters including absorption, distribution, metabolism, elimination and toxicity (ADMET) profiles of karanjin were also studied. The molecular dynamics (MD) simulations were performed with two selective karanjin docking complexes to analyze the dynamic behaviors and binding free energy at 100 ns time scale. In addition, frontier molecular orbitals (FMOs) and density-functional theory (DFT) were also investigated from computational quantum mechanism perspectives using the Avogadro-ORCA 1.2.0 platform. Karanjin complies with all five of Lipinski's drug-likeness rules with suitable ADMET profiles for therapeutic use. The docking scores (kcal/mol) showed comparatively higher potency against AD and PD associated targets than currently used standard drugs. Overall, the potential binding affinity from molecular docking, static thermodynamics feature from MD-simulation and other multiparametric drug-ability profiles suggest that karanjin could be considered as a suitable therapeutic lead for AD and PD treatment. Furthermore, the present results were strongly correlated with the earlier study on karanjin in an Alzheimer's animal model. However, necessary in vivo studies, clinical trials, bioavailability, permeability and safe dose administration, etc. must be required to use karanjin as a potential drug against AD and PD treatment, where the in silico results are more helpful to accelerate the drug development.

Authors+Show Affiliations

Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh 30450, Malaysia.Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh 30450, Malaysia.Faculty of Pharmacy, Centre of Excellence for Biomaterials Engineering, AIMST University, Bedong 08100, Malaysia.Division of Microbiology and NCDs, ICMR-Regional Medical Research Centre, Bhubaneswar 751023, India.School of Pharmacy, Monash University Malaysia, Bandar Sunway 47500, Malaysia.Department of Pharmacology, College of Pharmacy, King Khalid University, Abha 62529, Saudi Arabia.Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh 30450, Malaysia.Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh 30450, Malaysia.School of Biological Sciences, Faculty of Science and Technology, Quest International University Perak, Jalan Raja Permaisuri Bainun, Ipoh 30250, Malaysia.Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Royal College of Medicine Perak, Universiti Kuala Lumpur, Ipoh 30450, Malaysia.Department of Pharmacology, Sri Ramachandra Faculty of Pharmacy, Sri Ramachandra Institute of Higher Education and Research (DU), Porur, Chennai 600116, India.Department of Pharmaceutics, College of Pharmacy, King Khalid University, Abha 61421, Saudi Arabia.Department of Biotechnology, Siddaganga Institute of Technology, Tumakuru 572103, India.Center for Transdisciplinary Research, Department of Pharmacology, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai 600077, India.Faculty of Medicine, Bioscience and Nursing, MAHSA University, Jalan SP 2, Bandar Saujana Putra, Jenjarom 42610, Malaysia.Faculty of Pharmacy, Centre of Excellence for Biomaterials Engineering, AIMST University, Bedong 08100, Malaysia. Center for Transdisciplinary Research, Department of Pharmacology, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai 600077, India.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

35566187

Citation

Gnanaraj, Charles, et al. "In Silico Molecular Docking Analysis of Karanjin Against Alzheimer's and Parkinson's Diseases as a Potential Natural Lead Molecule for New Drug Design, Development and Therapy." Molecules (Basel, Switzerland), vol. 27, no. 9, 2022.
Gnanaraj C, Sekar M, Fuloria S, et al. In Silico Molecular Docking Analysis of Karanjin against Alzheimer's and Parkinson's Diseases as a Potential Natural Lead Molecule for New Drug Design, Development and Therapy. Molecules. 2022;27(9).
Gnanaraj, C., Sekar, M., Fuloria, S., Swain, S. S., Gan, S. H., Chidambaram, K., Rani, N. N. I. M., Balan, T., Stephenie, S., Lum, P. T., Jeyabalan, S., Begum, M. Y., Chandramohan, V., Thangavelu, L., Subramaniyan, V., & Fuloria, N. K. (2022). In Silico Molecular Docking Analysis of Karanjin against Alzheimer's and Parkinson's Diseases as a Potential Natural Lead Molecule for New Drug Design, Development and Therapy. Molecules (Basel, Switzerland), 27(9). https://doi.org/10.3390/molecules27092834
Gnanaraj C, et al. In Silico Molecular Docking Analysis of Karanjin Against Alzheimer's and Parkinson's Diseases as a Potential Natural Lead Molecule for New Drug Design, Development and Therapy. Molecules. 2022 Apr 29;27(9) PubMed PMID: 35566187.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In Silico Molecular Docking Analysis of Karanjin against Alzheimer's and Parkinson's Diseases as a Potential Natural Lead Molecule for New Drug Design, Development and Therapy. AU - Gnanaraj,Charles, AU - Sekar,Mahendran, AU - Fuloria,Shivkanya, AU - Swain,Shasank S, AU - Gan,Siew Hua, AU - Chidambaram,Kumarappan, AU - Rani,Nur Najihah Izzati Mat, AU - Balan,Tavamani, AU - Stephenie,Sarah, AU - Lum,Pei Teng, AU - Jeyabalan,Srikanth, AU - Begum,M Yasmin, AU - Chandramohan,Vivek, AU - Thangavelu,Lakshmi, AU - Subramaniyan,Vetriselvan, AU - Fuloria,Neeraj Kumar, Y1 - 2022/04/29/ PY - 2022/3/9/received PY - 2022/4/21/revised PY - 2022/4/25/accepted PY - 2022/5/14/entrez PY - 2022/5/15/pubmed PY - 2022/5/18/medline KW - ADMET KW - Alzheimer’s disease KW - Lipinski’s rule KW - Parkinson’s disease KW - bioinformatics KW - drug-likeness KW - in silico KW - karanjin KW - molecular dynamics JF - Molecules (Basel, Switzerland) JO - Molecules VL - 27 IS - 9 N2 - Parkinson's disease (PD) and Alzheimer's disease (AD) are neurodegenerative disorders that have emerged as among the serious health problems of the 21st century. The medications currently available to treat AD and PD have limited efficacy and are associated with side effects. Natural products are one of the most vital and conservative sources of medicines for treating neurological problems. Karanjin is a furanoflavonoid, isolated mainly from Pongamia pinnata with several medicinal plants, and has been reported for numerous health benefits. However, the effect of karanjin on AD and PD has not yet been systematically investigated. To evaluate the neuroprotective effect of karanjin, extensive in silico studies starting with molecular docking against five putative targets for AD and four targets for PD were conducted. The findings were compared with three standard drugs using Auto Dock 4.1 and Molegro Virtual Docker software. Additionally, the physiochemical properties (Lipinski rule of five), drug-likeness and parameters including absorption, distribution, metabolism, elimination and toxicity (ADMET) profiles of karanjin were also studied. The molecular dynamics (MD) simulations were performed with two selective karanjin docking complexes to analyze the dynamic behaviors and binding free energy at 100 ns time scale. In addition, frontier molecular orbitals (FMOs) and density-functional theory (DFT) were also investigated from computational quantum mechanism perspectives using the Avogadro-ORCA 1.2.0 platform. Karanjin complies with all five of Lipinski's drug-likeness rules with suitable ADMET profiles for therapeutic use. The docking scores (kcal/mol) showed comparatively higher potency against AD and PD associated targets than currently used standard drugs. Overall, the potential binding affinity from molecular docking, static thermodynamics feature from MD-simulation and other multiparametric drug-ability profiles suggest that karanjin could be considered as a suitable therapeutic lead for AD and PD treatment. Furthermore, the present results were strongly correlated with the earlier study on karanjin in an Alzheimer's animal model. However, necessary in vivo studies, clinical trials, bioavailability, permeability and safe dose administration, etc. must be required to use karanjin as a potential drug against AD and PD treatment, where the in silico results are more helpful to accelerate the drug development. SN - 1420-3049 UR - https://www.unboundmedicine.com/medline/citation/35566187/In_Silico_Molecular_Docking_Analysis_of_Karanjin_against_Alzheimer's_and_Parkinson's_Diseases_as_a_Potential_Natural_Lead_Molecule_for_New_Drug_Design_Development_and_Therapy_ DB - PRIME DP - Unbound Medicine ER -