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Valencene derived from essential oils of Psidium guajava L. as multi-target neurodegenerative inhibitor: A Computational study

Ram Lal Swagat Shrestha, Sujan Dhital , Nirmal Parajuli, Prabhat Neupane, Manila Poudel , Timila Shrestha, Samjhana Bharati, Binita Maharjan, Bishnu Marasini , Jhashanath Adhikari Subin

Abstract

The prevalence of neurodegenerative disorders such as Alzheimer’s, Parkinson’s, and Huntington’s have been gradually increasing in recent times. These diseases could be treated through the inhibition of acetylcholinesterase (AChE), monoamine oxidase B (MAOB), and huntingtin (HTT) proteins, respectively. This study aims to identify the compounds present in the oil of Psidium guajava L. using GC-MS analysis and to identify the potent neurodegenerative inhibitors through computational methods. The results revealed the presence of 42 different phytocompounds, and molecular docking calculations demonstrated firm binding of Valencene with the receptor proteins AChE, MAOB, and HTT, with binding affinities of -9.246 kcal/mol, -9.794 kcal/mol, and -9.541 kcal/mol, respectively, better to comparable with the references, Selegiline, Rivastigmine and Ciproxifan with binding affinities of -8.187 kcal/mol, -8.883 kcal/mol and -10.03 kcal/mol, respectively. All three complexes, MAOB-Valencene, AChE-Valencene, and HTT-Valencene demonstrated good geometrical stability, showing smooth RMSD curves and ligand RMSD of approximately 3.5 Å, 3.0 Å, and 6.0 Å, respectively, from 100 ns molecular dynamics simulation. The thermodynamic stability assessed through the MMPBSA method in terms of binding free energy changes revealed sustained spontaneity and feasibility of the adduct formations. The pharmacokinetic prediction supported the drug-like properties of Valencene. Comparative geometric stability and better thermodynamic stability of the complexes of Valencene than that of the reference drugs with key molecular targets in neurodegenerative diseases (MAOB, AChE, and HTT) suggested that it could be considered a hit candidate. Therefore, validation of Valencene through in vivo and in vitro experiments is recommended, as it could be a potential remedy for neurological disorders.

CH24117  Accepted 04 May 2025

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