MOLECULAR DOCKING AND SIMULATION STUDIES ON PHYTOCHEMICAL PROFILE OF CAPPARIS DECIDUA FOR INHIBITION OF ACETYLCHOLINESTERASE IN AD

Abstract

Alzheimer's disease (AD) is a sustained neurological disorder that is characterized by declination in cognition and loss of memory. The emergence of lesions such as neuritic plaques, neurofibrillary tangles (NFTs), cerebral amyloid angiopathy, neuronal loss, and cholinergic deficiency are markers suggestive of AD. Hence, indicating the potential significance to target associated proteins like amyloid precursor protein cleaving enzyme, cholinesterase such as butyrylcholinesterase (BuChE), and acetylcholinesterase (AChE) for therapeutic intervention. Despite ongoing studies there is no successful treatment measures for AD. Thereby, it becomes of utmost important to exploit bioactive substance from natural sources to improve the existing therapies and treat AD effectively. Capparis decidua a plant of medicinal importance from the family Capparacea contains abundance array of secondary metabolites like terpenoids, alkaloids, polyphenols,and phytosterols, which imparts various benefits like anti-inflammatory activitie, anti diabetic, anthelmintic, and antioxidant properties. The aim of this preliminary research is to explore the possibility of bio compounds derived from Capparis decidua as a potential candidate for treatment of AD. In order to achieve this, an initial in-silico assessment was performed by first evaluating the medicative value of Capparis decidua for the amelioration of AD. The analysis involved evaluation of the binding affinities of 55 phytochemicals obtained from Capparis decidua to the target protein acetylcholinesterase, AChE with the help of detailed docking study using Autodock Vina followed by validation of molecular docking study with the help of molecular dynamics simulations using 2020.3 version of GROMACS. Results demonstrated that Linolenic Acid and 2-hydroxycinnamic Acid exhibited lowest binding energy of -7.8 (Kcal/mol) and -7.1 (Kcal/mol), respectively. Hence the highest binding affinities towards the target, AChE. These scores which were comparably equivalent to the binding energy of the standard FDA approved control drug, Donepezil (-7.0 Kcal/mol). Further the stability of the complex system was investigated using molecular dynamic (MD) simulations. MD simulations utilize measures including root-mean-square deviations (RMSD), root-mean square fluctuation and Radius of gyration (Rg). Additionally, to this, various analyses were conducted to assess drug-likeness, bioactivity, permeation through the Blood-Brain Barrier (BBB), and bioavailability of the chosen phytochemicals, which hold the potential as therapeutic agents against neurodegenerative disorders like AD.