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Current Drug Targets

Editor-in-Chief

ISSN (Print): 1389-4501
ISSN (Online): 1873-5592

Review Article

Current Quest in Natural Bioactive Compounds for Alzheimer’s Disease: Multi-Targeted-Designed-Ligand Based Approach with Preclinical and Clinical Based Evidence

Author(s): Ashif Iqubal, Syed Obaidur Rahman, Musheer Ahmed, Pratichi Bansal, Md Rafi Haider, Mohammad Kashif Iqubal, Abul Kalam Najmi, Faheem Hyder Pottoo and Syed Ehtaishamul Haque*

Volume 22 , Issue 6 , 2021

Published on: 09 December, 2020

Page: [685 - 720] Pages: 36

DOI: 10.2174/1389450121999201209201004

Price: $65

Abstract

Alzheimer’s disease is a common and most chronic neurological disorder (NDs) associated with cognitive dysfunction. Pathologically, Alzheimer’s disease (AD) is characterized by the presence of β-amyloid (Aβ) plaques, hyper-phosphorylated tau proteins, and neurofibrillary tangles, however, persistence oxidative-nitrative stress, endoplasmic reticulum stress, mitochondrial dysfunction, inflammatory cytokines, pro-apoptotic proteins along with altered neurotransmitters level are common etiological attributes in its pathogenesis. Rivastigmine, memantine, galantamine, and donepezil are FDA approved drugs for symptomatic management of AD, whereas tacrine has been withdrawn because of hepatotoxic profile. These approved drugs only exert symptomatic relief and exhibit poor patient compliance. In the current scenario, the number of published evidence shows the neuroprotective potential of naturally occurring bioactive molecules via their antioxidant, anti-inflammatory, antiapoptotic and neurotransmitter modulatory properties. Despite their potent therapeutic implications, concerns have arisen in context to their efficacy and probable clinical outcome. Thus, to overcome these glitches, many heterocyclic and cyclic hydrocarbon compounds inspired by natural sources have been synthesized and showed improved therapeutic activity. Computational studies (molecular docking) have been used to predict the binding affinity of these natural bioactive as well as synthetic compounds derived from natural sources for the acetylcholine esterase, α/β secretase Nuclear Factor kappa- light-chain-enhancer of activated B cells (NF-kB), Nuclear factor erythroid 2-related factor 2(Nrf2) and other neurological targets. Thus, in this review, we have discussed the molecular etiology of AD, focused on the pharmacotherapeutics of natural products, chemical and pharmacological aspects and multi-targeted designed ligands (MTDLs) of synthetic and semisynthetic molecules derived from the natural sources along with some important on-going clinical trials.

Keywords: Neurodegeneration, natural products, tau proteins, molecular docking, dementia, computational studies; clinical trials.

Graphical Abstract

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