PMID- 33302832
OWN - NLM
STAT- MEDLINE
DCOM- 20211126
LR  - 20211126
IS  - 1873-5592 (Electronic)
IS  - 1389-4501 (Linking)
VI  - 22
IP  - 6
DP  - 2021
TI  - Current Quest in Natural Bioactive Compounds for Alzheimer's Disease: 
      Multi-Targeted-Designed-Ligand Based Approach with Preclinical and Clinical Based 
      Evidence.
PG  - 685-720
LID - 10.2174/1389450121999201209201004 [doi]
AB  - 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 beta-amyloid (Abeta) 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      symptomatic management of AD, whereas tacrine has been withdrawn because of 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, alpha/beta 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.
CI  - Copyright(c) Bentham Science Publishers; For any queries, please email at 
      epub@benthamscience.net.
FAU - Iqubal, Ashif
AU  - Iqubal A
AD  - Department of Pharmacology, School of Pharmaceutical Education and Research, 
      JamiaHamdard, New Delhi-110062, India.
FAU - Rahman, Syed Obaidur
AU  - Rahman SO
AD  - Department of Pharmaceutical Medicine, School of Pharmaceutical Education and 
      Research, JamiaHamdard, New Delhi-110062, India.
FAU - Ahmed, Musheer
AU  - Ahmed M
AD  - Department of Pharmaceutics, School of Pharmaceutical Education and Research, 
      JamiaHamdard, New Delhi-110062, India.
FAU - Bansal, Pratichi
AU  - Bansal P
AD  - Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and 
      Research, JamiaHamdard, New Delhi-110062, India.
FAU - Haider, Md Rafi
AU  - Haider MR
AD  - Department of Pharmaceutical Chemistry, School of Pharmaceutical Education and 
      Research, JamiaHamdard, New Delhi-110062, India.
FAU - Iqubal, Mohammad Kashif
AU  - Iqubal MK
AD  - Department of Pharmaceutics, School of Pharmaceutical Education and Research, 
      JamiaHamdard, New Delhi-110062, India.
FAU - Najmi, Abul Kalam
AU  - Najmi AK
AD  - Department of Pharmacology, School of Pharmaceutical Education and Research, 
      JamiaHamdard, New Delhi-110062, India.
FAU - Pottoo, Faheem Hyder
AU  - Pottoo FH
AD  - Department of Pharmacology, College of Clinical Pharmacy, Imam Abdulrahman Bin 
      Faisal, University, P.O.BOX 1982, Damman, 31441, Saudi Arabia.
FAU - Haque, Syed Ehtaishamul
AU  - Haque SE
AD  - Department of Pharmacology, School of Pharmaceutical Education and Research, 
      JamiaHamdard, New Delhi-110062, India.
LA  - eng
PT  - Journal Article
PT  - Review
PL  - United Arab Emirates
TA  - Curr Drug Targets
JT  - Current drug targets
JID - 100960531
RN  - 0 (Biological Products)
RN  - 0 (Ligands)
SB  - IM
MH  - *Alzheimer Disease/drug therapy
MH  - Biological Products/*pharmacology
MH  - Drug Design
MH  - Humans
MH  - Ligands
MH  - Molecular Docking Simulation
OTO - NOTNLM
OT  - Neurodegeneration
OT  - computational studies; clinical trials
OT  - dementia
OT  - molecular docking
OT  - natural products
OT  - tau proteins
EDAT- 2020/12/12 06:00
MHDA- 2021/11/27 06:00
CRDT- 2020/12/11 05:34
PHST- 2020/05/29 00:00 [received]
PHST- 2020/08/12 00:00 [revised]
PHST- 2020/08/23 00:00 [accepted]
PHST- 2020/12/12 06:00 [pubmed]
PHST- 2021/11/27 06:00 [medline]
PHST- 2020/12/11 05:34 [entrez]
AID - CDT-EPUB-112248 [pii]
AID - 10.2174/1389450121999201209201004 [doi]
PST - ppublish
SO  - Curr Drug Targets. 2021;22(6):685-720. doi: 10.2174/1389450121999201209201004.