Title:Computational Analysis of Bacopa monnieri (L.) Wettst. Compounds for
Drug Development against Neurodegenerative Disorders
Volume: 19
Issue: 1
Author(s): Satyam Sangeet*, Arshad Khan, Saurov Mahanta, Nabamita Roy, Sanjib Kumar Das, Yugal Kishore Mohanta, Muthupandian Saravanan, Hui Tag and Pallabi Kalita Hui*
Affiliation:
- Department of Biological Science and Engineering, Maulana Azad National Institute of Technology, Bhopal, Madhya Pradesh,
462033, India
- Department of Biotechnology, National Institute of Technology (NIT) Arunachal Pradesh, Yupia,
79112, Arunachal Pradesh, India
Keywords:
Neurotrophins, Bacopa monnieri, molecular docking, molecular dynamics, ADME, phytochemical.
Abstract:
Aim: With several experimental studies establishing the role of Bacopa monnieri as an effective
neurological medication, less focus has been employed to explore how effectively Bacopa monnieri brings
about this property. The current work focuses on understanding the molecular interaction of the phytochemicals
of the plant against different neurotrophic factors to explore their role and potential as potent
anti-neurodegenerative drugs.
Background: Neurotrophins play a crucial role in the development and regulation of neurons. Alterations
in the functioning of these Neurotrophins lead to several Neurodegenerative Disorders. Albeit engineered
medications are accessible for the treatment of Neurodegenerative Disorders, due to their numerous side
effects, it becomes imperative to formulate and synthesize novel drug candidates.
Objective: This study aims to investigate the potential of Bacopa monnieri phytochemicals as potent antineurodegenerative
drugs by inspecting the interactions between Neurotrophins and target proteins.
Methods: The current study employs molecular docking and molecular dynamic simulation studies to examine
the molecular interactions of phytochemicals with respective Neurotrophins. Further inspection of
the screened phytochemicals was performed to analyze the ADME-Tox properties in order to classify the
screened phytochemicals as potent drug candidates.
Results: The phytochemicals of Bacopa monnieri were subjected to in-silico docking with the respective
Neurotrophins. Vitamin E, Benzene propanoic acid, 3,5-bis (1,1- dimethylethyl)- 4hydroxy-, methyl ester
(BPA), Stigmasterol, and Nonacosane showed an excellent binding affinity with their respective Neurotrophins
(BDNF, NT3, NT4, NGF). Moreover, the molecular dynamic simulation studies revealed that BPA
and Stigmasterol show a very stable interaction with NT3 and NT4, respectively, suggesting their potential
role as a drug candidate. Nonacosane exhibited a fluctuating binding behavior with NGF which can be accounted
for by its long linear structure. ADME-Tox studies further confirmed the potency of these phytochemicals
as BPA violated no factors and Vitamin E, Stigmasterol and Nonacosane violated 1 factor for
Lipinski’s rule. Moreover, their high human intestinal absorption and bioavailability score along with their
classification as non-mutagen in the Ames test makes these compounds more reliable as potent antineurodegenerative
drugs.
Conclusion: Our study provides an in-silico approach toward understanding the anti-neurodegenerative
property of Bacopa monnieri phytochemicals and establishes the role of four major phytochemicals which
can be utilized as a replacement for synthetic drugs against several neurodegenerative disorders.
