PMID- 27783974
OWN - NLM
STAT- MEDLINE
DCOM- 20170228
LR  - 20181202
IS  - 1768-3254 (Electronic)
IS  - 0223-5234 (Linking)
VI  - 124
DP  - 2016 Nov 29
TI  - Synthesis of new donepezil analogues and investigation of their effects on 
      cholinesterase enzymes.
PG  - 1026-1040
LID - S0223-5234(16)30904-7 [pii]
LID - 10.1016/j.ejmech.2016.10.042 [doi]
AB  - Donepezil (DNP), an acetylcholinesterase (AChE) inhibitor, is one of the most 
      preferred choices in Alzheimer diseases (AD) therapy. In the present study, 38 
      new DNP analogues were synthesized. Structures of the synthesized compounds 
      (1-38) were elucidated by IR, (1)H NMR, (13)C NMR and HRMS spectroscopic methods 
      and elemental analysis. Inhibitory potential of the compounds on cholinesterase 
      enzymes was investigated. None of the compounds displayed significant activity on 
      butyrylcholinesterase (BChE) enzyme. On the other hand, compounds 26-29 indicated 
      important inhibitory activity on AChE enzyme. Kinetic studies were performed in 
      order to observe the effects of the most active compounds on substrate-enzyme 
      relationship. Cytotoxicity studies and theoretical calculation of pharmacokinetic 
      properties were also carried out to get an information about toxicity and 
      pharmacokinetic profiles of the compounds. The compounds 26-29 were found to be 
      nontoxic at their effective concentrations against AChE. A good pharmacokinetic 
      profile was predicted for these compounds. Docking studies were performed for the 
      most active compounds 26-29 and interaction modes with enzyme active sites were 
      determined. Docking studies revealed that there is a strong interaction between 
      the active sites of AChE enzyme and analyzed compounds.
CI  - Copyright (c) 2016 Elsevier Masson SAS. All rights reserved.
FAU - Saglik, Begum Nurpelin
AU  - Saglik BN
AD  - Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 
      26470 Eskisehir, Turkey; Doping and Narcotic Compounds Analysis Laboratory, 
      Faculty of Pharmacy, Anadolu University, 26470 Eskisehir, Turkey.
FAU - Ilgin, Sinem
AU  - Ilgin S
AD  - Department of Toxicology, Faculty of Pharmacy, Anadolu University, 26470 
      Eskisehir, Turkey.
FAU - Ozkay, Yusuf
AU  - Ozkay Y
AD  - Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, 
      26470 Eskisehir, Turkey; Doping and Narcotic Compounds Analysis Laboratory, 
      Faculty of Pharmacy, Anadolu University, 26470 Eskisehir, Turkey. Electronic 
      address: yozkay@anadolu.edu.tr.
LA  - eng
PT  - Journal Article
DEP - 20161019
PL  - France
TA  - Eur J Med Chem
JT  - European journal of medicinal chemistry
JID - 0420510
RN  - 0 (Cholinesterase Inhibitors)
RN  - 0 (Indans)
RN  - 0 (Piperidines)
RN  - 8SSC91326P (Donepezil)
RN  - EC 3.1.1.7 (Acetylcholinesterase)
RN  - EC 3.1.1.8 (Butyrylcholinesterase)
SB  - IM
MH  - Acetylcholinesterase/chemistry/metabolism
MH  - Animals
MH  - Butyrylcholinesterase/chemistry/metabolism
MH  - Chemistry Techniques, Synthetic
MH  - Cholinesterase Inhibitors/*chemical synthesis/chemistry/metabolism/*pharmacology
MH  - Donepezil
MH  - *Drug Design
MH  - Electrophorus
MH  - Indans/*chemical synthesis/chemistry/metabolism/*pharmacology
MH  - Kinetics
MH  - Mice
MH  - Molecular Docking Simulation
MH  - NIH 3T3 Cells
MH  - Piperidines/*chemical synthesis/chemistry/metabolism/*pharmacology
MH  - Protein Conformation
MH  - Structure-Activity Relationship
OTO - NOTNLM
OT  - Acetylcholinesterase
OT  - Alzheimer diseases
OT  - Docking
OT  - Indanone
OT  - Piperazine
EDAT- 2016/10/27 06:00
MHDA- 2017/03/01 06:00
CRDT- 2016/11/07 06:00
PHST- 2016/10/07 00:00 [received]
PHST- 2016/10/17 00:00 [revised]
PHST- 2016/10/18 00:00 [accepted]
PHST- 2016/11/07 06:00 [entrez]
PHST- 2016/10/27 06:00 [pubmed]
PHST- 2017/03/01 06:00 [medline]
AID - S0223-5234(16)30904-7 [pii]
AID - 10.1016/j.ejmech.2016.10.042 [doi]
PST - ppublish
SO  - Eur J Med Chem. 2016 Nov 29;124:1026-1040. doi: 10.1016/j.ejmech.2016.10.042. 
      Epub 2016 Oct 19.