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bioRxiv · 10.1101/2022.03.30.486025

In silico analysis of Bacopa monnieri (L.) Wettst. compounds for drug development against Neurodegenerative Disorders

Sangeet, S.·Khan, A.·Mahanta, S.·Roy, N.·Das, S. K.·Mohanta, Y. K.·Saravanan, M.·Tag, H.·Hui, P. K.
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Abstract

Neurotrophins play a crucial role in the development and regulation of neurons. Alterations in the functioning of these Neurotrophins leads to several Neurodegenerative Disorders. Albeit engineered medications which are accessible for the treatment of Neurodegenerative Disorders, due to their numerous side-effects, it becomes imperative to formulate and synthesize novel drug candidates. Plants could be utilized as an alternative for these manufactured medications because of their low incidental effects in contrast with the engineered drugs. Bacopa monnieri has been traditionally known to be utilized to treat Neurodegenerative Disorders. Therefore, in current study an in-silico based study was carried out to evaluate the pharmacological effect of Bacopa monnieri. Molecular Docking was carried out to screen the active phytochemicals of Bacopa monnieri which can act as potential drug candidates against the causative proteins of Neurodegenerative Disorders. A total of 105 biologically active phytochemicals from Bacopa monnieri were docked against the receptors of brain-derived neurotrophic factor, neurotrophin-3, neurotrophin-4, and nerve growth factor. Based on molecular docking study it was observed that the phytocompounds Vitamin E, Benzene propanoic acid, 3,5-bis(1,1dimethylethyl)4-hydroxy-, methyl ester (BPA), Stigmasterol, and Nonacosane of Bacopa monnieri significantly fits to the active residues of the four selected drug targets. Further Molecular Dynamics simulation study was performed to examine the stability of the binding of these phytochemicals with the selected targets. Drug likeness properties as well as related physico-chemical properties were analyzed through ADMETox study. Our findings suggested that the phytocompounds Vitamin E, BPA, Stigmasterol and Nonacosane significantly bind against brain-derived neurotrophic factor, neurotrophin-3, neurotrophin4, and nerve growth factor, respectively which may be the potential drug candidates for the treatment of neurodegenerative disorders. Graphic Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=140 SRC="FIGDIR/small/486025v1_ufig1.gif" ALT="Figure 1"> View larger version (55K): org.highwire.dtl.DTLVardef@2c39aforg.highwire.dtl.DTLVardef@17f4fd9org.highwire.dtl.DTLVardef@1534e13org.highwire.dtl.DTLVardef@2ad383_HPS_FORMAT_FIGEXP M_FIG C_FIG

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Sangeet, S., Khan, A., Mahanta, S., Roy, N., Das, S. K., Mohanta, Y. K., Saravanan, M., Tag, H., Hui, P. K.. 2022-03-31. In silico analysis of Bacopa monnieri (L.) Wettst. compounds for drug development against Neurodegenerative Disorders. https://doi.org/10.1101/2022.03.30.486025

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