INVESTIGATING MULTITARGET POTENTIAL OF MUCUNA PRURIENS AGAINST PARKINSON'S DISEASE: INSIGHTS FROM MOLECULAR DOCKING, MMGBSA, PHARMACOPHORE MODELLING, MD SIMULATIONS AND ADMET ANALYSIS

Author:

FATHIMA C. ZAKIYAORCID,JAMES JAINEY P.,SRINIVASA MAHENDRA GOWDRUORCID,T. J SINDHUORCID,B. M. MARIYAM JOUHARAORCID,REVANASIDDAPPA B. C.,D. GHATE SUDEEP

Abstract

Objective: Mucuna pruriens (Velvet beans) is a leguminous plant recognised in Vedic therapy as an anti-Parkinsonism agent. The plant is known as the natural reservoir for levodopa. The study aims to evaluate the multitarget inhibitory potency of active constituents present in Mucuna pruriens using in silico tools. Methods: The phytoconstituents present in Mucuna pruriens were retrieved from the IMPPAT database. The physicochemical and toxicity parameters of phytoconstituents were evaluated using Qikprop and ProTox-3. The inhibitory potential of phytoconstituents on the enzymes Monoamine Oxidase-B (MAO-B), Acetylcholinesterase (AChE), and Catechol-O-Methyltransferase (COMT) was evaluated using in silico techniques, including molecular docking, pharmacophore modelling, and molecular dynamics simulations, conducted with Schrödinger software programs. Results: The active constituents comply with Lipinski’s rule for drug-likeness. Further, the molecular docking studies revealed the phytoconstituent luteolin and acacetin showed promising multitargeted inhibitory properties. Especially luteolin (-11.504 kcal/mol) and acacetin (-10.620 kcal/mol) have obtained excellent docking scores with MAO-B, whereas the known drug levodopa showed a docking score of-8.501 kcal/mol. The pharmacophore modelling revealed that donor, acceptor, and aromatic features present in luteolin and acacetin are the essential pharmacophoric features accountable for biological activity. The simulation study generated the stability of the protein-ligand complex and found that luteolin showed a stable complex with MAO-B. Conclusion: Based on these findings, the result of the current study can be used to develop a novel luteolin-based drug for treating Parkinson’s disease with preferred structural modification. However, additional and more comprehensive research is required on this compound.

Publisher

Innovare Academic Sciences Pvt Ltd

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