PMID- 36149034
OWN - NLM
STAT- MEDLINE
DCOM- 20230103
LR  - 20230103
IS  - 1521-4184 (Electronic)
IS  - 0365-6233 (Linking)
VI  - 356
IP  - 1
DP  - 2023 Jan
TI  - Development of new Alzheimer's disease drug candidates using donepezil as a key 
      model.
PG  - e2200398
LID - 10.1002/ardp.202200398 [doi]
AB  - Alzheimer's disease (AD) is one of the most prevalent geriatric diseases and a 
      significant cause of high mortality. This crippling disorder is becoming more 
      prevalent at an unprecedented rate, which has led to an increase in the financial 
      cost of caring. It is a pathologically complicated, multifactorial disease 
      characterized by beta-amyloid precipitation, beta-amyloid oligomer production, decrease 
      in cholinergic function, and dysregulation of other neurotransmitter systems. Due 
      to the pathogenic complexity of AD, multitarget drugs that can simultaneously 
      alternate multiple biological targets may enhance the therapeutic efficacy. 
      Donepezil (DNP) is the most potent approved drug for the treatment of AD. It has 
      a remarkable effect on a number of AD-related processes, including cholinesterase 
      activity, anti-Abeta aggregation, oxidative stress, and more. DNP resembles an 
      excellent scaffold to be hybridized with other pharmacophoric moieties having 
      biological activity against AD pathological factors. There have been significant 
      attempts made to modify the structure of DNP to create new bioactive chemical 
      entities with novel structural patterns. In this review, we highlight recent 
      advances in the development of multiple-target DNP-hybridized models for the 
      treatment of AD that can be used in the future in the rational design of new 
      potential AD therapeutics. The design and development of new drug candidates for 
      the treatment of AD using DNP as a molecular scaffold have also been reviewed and 
      summarized.
CI  - (c) 2022 Deutsche Pharmazeutische Gesellschaft.
FAU - Eissa, Kholoud I
AU  - Eissa KI
AD  - Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Cairo 
      University, Cairo, Egypt.
FAU - Kamel, Mona M
AU  - Kamel MM
AD  - Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Cairo 
      University, Cairo, Egypt.
FAU - Mohamed, Lamia W
AU  - Mohamed LW
AD  - Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Cairo 
      University, Cairo, Egypt.
FAU - Kassab, Asmaa E
AU  - Kassab AE
AUID- ORCID: 0000-0002-6091-829X
AD  - Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Cairo 
      University, Cairo, Egypt.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20220923
PL  - Germany
TA  - Arch Pharm (Weinheim)
JT  - Archiv der Pharmazie
JID - 0330167
RN  - 8SSC91326P (Donepezil)
RN  - 0 (Cholinesterase Inhibitors)
RN  - EC 3.1.1.7 (Acetylcholinesterase)
RN  - 0 (Amyloid beta-Peptides)
SB  - IM
MH  - Humans
MH  - Aged
MH  - Donepezil/pharmacology/chemistry
MH  - *Alzheimer Disease/drug therapy
MH  - Cholinesterase Inhibitors/pharmacology/chemistry
MH  - Structure-Activity Relationship
MH  - Acetylcholinesterase/metabolism
MH  - Amyloid beta-Peptides
OTO - NOTNLM
OT  - Alzheimer's disease
OT  - donepezil
OT  - hybrid
OT  - multitarget
EDAT- 2022/09/24 06:00
MHDA- 2023/01/04 06:00
CRDT- 2022/09/23 08:33
PHST- 2022/09/03 00:00 [revised]
PHST- 2022/07/27 00:00 [received]
PHST- 2022/09/05 00:00 [accepted]
PHST- 2022/09/24 06:00 [pubmed]
PHST- 2023/01/04 06:00 [medline]
PHST- 2022/09/23 08:33 [entrez]
AID - 10.1002/ardp.202200398 [doi]
PST - ppublish
SO  - Arch Pharm (Weinheim). 2023 Jan;356(1):e2200398. doi: 10.1002/ardp.202200398. 
      Epub 2022 Sep 23.