Please wait, while we are loading the content...
Please wait, while we are loading the content...
| Content Provider | frontiers |
|---|---|
| Author | Khalid, Asaad Khan, Waqasuddin Zia, Komal Azizuddin, Ahsan, Waquar Alhazmi, Hassan A. Abdalla, Ashraf N. Najmi, Asim Khan, Andleeb Bouyahya, Abdelhakim Ul-Haq, Zaheer Khan, Ajmal |
| Abstract | Currently, acetylcholinesterase (AChE) inhibiting drugs in clinical use, such as tacrine, donepezil, rivastigmine, and galanthamine, are associated with serious side effects and short half-lives. In recent years, numerous phytochemicals have been identified as inhibitors of cholinesterases with potential applications in the management of Alzheimer's disease (AD). In this study three natural coumarins, 2'-O-ethylmurrangatin (1), murranganone (2), and paniculatin (3) isolated previously by our group from the leaves of Murraya paniculata, were tested against the two cholinesterases (ChE) enzymes, AChE and butyrylcholinesterase (BChE) using in vitro assay. Molecular docking was performed to highlight the structural properties that contribute to the molecular recognition pattern in the inhibition of ChE and the structural differences resulting in the selectivity of these compounds toward AChE. Classical enzyme inhibition kinetics data suggested that compounds 2 and 3 were potent inhibitors of AChE and BChE having non-competitive and mixed-type behavior, while 1 was found inactive against both enzymes. The findings from molecular docking studies revealed the competitive and non-competitive inhibition mechanisms of compounds 2 and 3 against both enzymes. Molecular docking and simulations have revealed that hydrogen bonding, mediated by ketone and hydroxyl functionalities in various positions, significantly contributes to the binding of the inhibitor to the receptor. According to MD simulation studies, the stability of the ligand-AChE complex for the most active compound (3) is found to be comparable to that of the widely used drug Tacrine. In addition, to evaluate the drug-likeness of compounds, in silico ADME evaluation was performed, and the compounds presented good ADME profiles. Data suggested that the coumarin nucleus having diverse side chains at the C-8 position can serve as a potential inhibitor of cholinesterases and can act as a lead to develop a new semisynthetic drug for the treatment of AD. |
| ISSN | 16639812 |
| DOI | 10.3389/fphar.2023.1133809 |
| Volume Number | 14 |
| Journal | Frontiers in Pharmacology |
| Language | English |
| Publisher Date | 2023-03-09 |
| Access Restriction | Open |
| Subject Keyword | Butyrylcholinesterase Ligand-enzyme interactions Molecular docking MD simulation Acetylcholinesterase Inhibition kinetics Natural coumarins |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology Pharmacology (medical) |
National Digital Library of India (NDLI) is a virtual repository of learning resources which is not just a repository with search/browse facilities but provides a host of services for the learner community. It is sponsored and mentored by Ministry of Education, Government of India, through its National Mission on Education through Information and Communication Technology (NMEICT). Filtered and federated searching is employed to facilitate focused searching so that learners can find the right resource with least effort and in minimum time. NDLI provides user group-specific services such as Examination Preparatory for School and College students and job aspirants. Services for Researchers and general learners are also provided. NDLI is designed to hold content of any language and provides interface support for 10 most widely used Indian languages. It is built to provide support for all academic levels including researchers and life-long learners, all disciplines, all popular forms of access devices and differently-abled learners. It is designed to enable people to learn and prepare from best practices from all over the world and to facilitate researchers to perform inter-linked exploration from multiple sources. It is developed, operated and maintained from Indian Institute of Technology Kharagpur.
Learn more about this project from here.
NDLI is a conglomeration of freely available or institutionally contributed or donated or publisher managed contents. Almost all these contents are hosted and accessed from respective sources. The responsibility for authenticity, relevance, completeness, accuracy, reliability and suitability of these contents rests with the respective organization and NDLI has no responsibility or liability for these. Every effort is made to keep the NDLI portal up and running smoothly unless there are some unavoidable technical issues.
Ministry of Education, through its National Mission on Education through Information and Communication Technology (NMEICT), has sponsored and funded the National Digital Library of India (NDLI) project.
| Sl. | Authority | Responsibilities | Communication Details |
|---|---|---|---|
| 1 | Ministry of Education (GoI), Department of Higher Education |
Sanctioning Authority | https://www.education.gov.in/ict-initiatives |
| 2 | Indian Institute of Technology Kharagpur | Host Institute of the Project: The host institute of the project is responsible for providing infrastructure support and hosting the project | https://www.iitkgp.ac.in |
| 3 | National Digital Library of India Office, Indian Institute of Technology Kharagpur | The administrative and infrastructural headquarters of the project | Dr. B. Sutradhar bsutra@ndl.gov.in |
| 4 | Project PI / Joint PI | Principal Investigator and Joint Principal Investigators of the project |
Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon |
| 5 | Website/Portal (Helpdesk) | Queries regarding NDLI and its services | support@ndl.gov.in |
| 6 | Contents and Copyright Issues | Queries related to content curation and copyright issues | content@ndl.gov.in |
| 7 | National Digital Library of India Club (NDLI Club) | Queries related to NDLI Club formation, support, user awareness program, seminar/symposium, collaboration, social media, promotion, and outreach | clubsupport@ndl.gov.in |
| 8 | Digital Preservation Centre (DPC) | Assistance with digitizing and archiving copyright-free printed books | dpc@ndl.gov.in |
| 9 | IDR Setup or Support | Queries related to establishment and support of Institutional Digital Repository (IDR) and IDR workshops | idr@ndl.gov.in |
|
Loading...
|