Pharmacokinetic and Molecular Docking Studies of Plant-Derived Natural Compounds to Exploring Potential Anti-Alzheimer Activity

Abstract

Alzheimer's disease (AD) is the leading cause of dementia, accounts for 60 to 80 percent cases. Two main factors called β-amyloid (Aβ) plaques and tangles are prime suspects in damaging and killing nerve cells. However, oxidative stress, the process which produces free radicals in cells, is believed to promote its progression to the extent that it may responsible for the cognitive and functional decline observed in AD. As of today there are few FDA approved drugs in the market for treatment, but their cholinergic adverse effect, potentially distressing toxicity and limited targets in AD pathology limits their use. Therefore, it is crucial to find an effective compounds to combat AD. We choose 45 plant-derived natural compounds that have antioxidant properties to slow down disease progression by quenching free redicals or promoting endogenous antioxidant capacity. However, we performed molecular docking studies to investigate the binding interactions between natural compounds and 13 various anti-Alzheimer drug targets. Three known Cholinesterase inhibitors (Donepezil, Galantamine and Rivastigmine) were taken as reference drugs over natural compounds for comparison and drug-likeness studies. Few of these compounds showed good inhibitory activity besides anti-oxidant activity. Most of these compounds followed pharmacokinetics properties that make them potentially promising drug candidates for the treatment of Alzheimer's disease. Graphical Abstract : Pharmacokinatics and Molecular docking studies of 45 natural antioxidant compounds with most known Alzheimer asscociated targets. Administration (FDA) have approved two medications-cholinesterase inhibitors and Memantine. Over the past decade, much of the research on Alzheimer disease (AD) has focused on oxidative stress mechanisms and its importance in disease pathogenesis. The net effect of oxygen radicals is damaging, such damage present in AD includes advanced glycation end products [2], nitration [3], lipid peroxidation adduction products [4-5] as well as carbonyl-modified neurofilament protein and free carbonyls [6-7]. Significantly, this damage involves all neurons at risk to death in AD, not just those containing neurofibrillary tangles.Nature has gifted us lots of natural remedies in the form of fruits, leaves, bark, vegetables and nuts, etc. The various ranges of bioactive nutrients present in these natural products play a vital role in prevention and cure of various neurodegenerative diseases, such as AD,Parkinson's disease and other neuronal dysfunctions. Previous studies suggested that the naturally occurring phytochemicals, such as polyphenolic antioxidants found in fruits, vegetables, herbs and nuts, may potentially hinder neurodegeneration, and improve memory and cognitive functions.

Synthesis, Characterization, Molecular Docking, and Anticancer Evaluation of 4‐Thiazolidinone Analogues

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Electrophoretic Light Scattering and Electrochemical Impedance Spectroscopy Studies of Lipid Bilayers Modified by Cinnamic Acid and Its Hydroxyl Derivatives

“…Because each threshold is a multiple of 5, the rule was called Ro5. Molecules not complying with more than one of these rules may have problems with bioavailability [ 21 ].…”

Structure-Guided Approach to Identify Potential Inhibitors of Large Envelope Protein to Prevent Hepatitis B Virus Infection

“…In case of toxicity, all four compounds have non-AMES toxicity, are noncarcinogenic, and have no carcinogenicity (three-class) required. To distinguish any unfavorable toxic properties of novel hits, TOPKAT software was also used [54]. Several descriptors such as the Ames mutagenicity test, weight of evidence carcinogenicity (v5.1) (WOE), rat oral LD50, skin irritation, skin sensitization, and aerobic biodegradability [55, 56] were investigated ().…”