Title:Current Quest in Natural Bioactive Compounds for Alzheimer’s Disease: Multi-Targeted-Designed-Ligand Based Approach with Preclinical and Clinical Based Evidence
Volume: 22
Issue: 6
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*
Affiliation:
- Department of Pharmacology, School of Pharmaceutical Education and Research, JamiaHamdard, New Delhi-110062,India
Keywords:
Neurodegeneration, natural products, tau proteins, molecular docking, dementia, computational studies; clinical
trials.
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FDA approved drugs for symptomatic management of AD, whereas tacrine has been withdrawn because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.
