PMID- 24794747
OWN - NLM
STAT- MEDLINE
DCOM- 20150930
LR  - 20171116
IS  - 1464-3391 (Electronic)
IS  - 0968-0896 (Linking)
VI  - 22
IP  - 12
DP  - 2014 Jun 15
TI  - Novel aromatic-polyamine conjugates as cholinesterase inhibitors with notable 
      selectivity toward butyrylcholinesterase.
PG  - 3213-9
LID - S0968-0896(14)00241-7 [pii]
LID - 10.1016/j.bmc.2014.03.045 [doi]
AB  - Three types of aromatic-polyamine conjugates (6a-6s) were designed, synthesized 
      and evaluated as potential inhibitors for cholinesterases (ChEs). The results 
      showed that anthraquinone-polyamine conjugates (AQPCs) exhibited the most potent 
      acetylcholinesterase (AChE) inhibitory activity with IC50 values from 1.50 to 
      11.13 muM. Anthracene-polyamine conjugates (APCs) showed a surprising selectivity 
      (from 76- to 3125-fold) and were most potent at inhibiting butyrylcholinesterase 
      (BChE), with IC50 values from 0.016 to 0.657 muM. A Lineweaver-Burk plot and 
      molecular modeling studies indicated that the representative compounds, 6l and 
      6k, targeted both the catalytic active site (CAS) and the peripheral anionic site 
      (PAS) of ChEs. Furthermore, APCs did not affect HepG2 cell viability at the 
      concentration of 100 muM. Consequently, these polyamine conjugates could be 
      thoroughly and systematically studied for the treatment of AD.
CI  - Copyright (c) 2014 Elsevier Ltd. All rights reserved.
FAU - Hong, Chen
AU  - Hong C
AD  - Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, 
      Kaifeng 475004, People's Republic of China.
FAU - Luo, Wen
AU  - Luo W
AD  - Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, 
      Kaifeng 475004, People's Republic of China. Electronic address: 
      luowen83@henu.edu.cn.
FAU - Yao, Dong
AU  - Yao D
AD  - Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, 
      Kaifeng 475004, People's Republic of China.
FAU - Su, Ya-Bin
AU  - Su YB
AD  - Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, 
      Kaifeng 475004, People's Republic of China.
FAU - Zhang, Xin
AU  - Zhang X
AD  - Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, 
      Kaifeng 475004, People's Republic of China.
FAU - Tian, Run-Guo
AU  - Tian RG
AD  - Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, 
      Kaifeng 475004, People's Republic of China.
FAU - Wang, Chao-Jie
AU  - Wang CJ
AD  - Key Laboratory of Natural Medicine and Immuno-Engineering, Henan University, 
      Kaifeng 475004, People's Republic of China. Electronic address: 
      wcjsxq@henu.edu.cn.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140413
PL  - England
TA  - Bioorg Med Chem
JT  - Bioorganic & medicinal chemistry
JID - 9413298
RN  - 0 (2-(4-aminobutylamino)-N-(anthracen-9-yl)acetamide hydrochloride)
RN  - 0 (2-(6-aminohexylamino)-N-(anthracen-9-yl)acetamide hydrochloride)
RN  - 0 (Acetamides)
RN  - 0 (Amyloid beta-Peptides)
RN  - 0 (Anthracenes)
RN  - 0 (Cholinesterase Inhibitors)
RN  - 0 (Polyamines)
RN  - EC 3.1.1.8 (Butyrylcholinesterase)
RN  - EH46A1TLD7 (anthracene)
SB  - IM
MH  - Acetamides/chemistry/*pharmacology
MH  - Alzheimer Disease/*drug therapy/enzymology
MH  - Amyloid beta-Peptides
MH  - Anthracenes/chemistry/*pharmacology
MH  - Binding Sites
MH  - Butyrylcholinesterase/*chemistry
MH  - Catalytic Domain
MH  - Cell Proliferation/*drug effects
MH  - Cholinesterase Inhibitors/chemistry/*pharmacology
MH  - Drug Design
MH  - Hep G2 Cells
MH  - Humans
MH  - Models, Molecular
MH  - Molecular Docking Simulation
MH  - Molecular Structure
MH  - Polyamines/chemistry/*pharmacology
MH  - Protein Conformation
MH  - Structure-Activity Relationship
OTO - NOTNLM
OT  - Acetylcholinesterase
OT  - Alzheimer's disease
OT  - Butyrylcholinesterase
OT  - Polyamine conjugates
EDAT- 2014/05/06 06:00
MHDA- 2015/10/01 06:00
CRDT- 2014/05/06 06:00
PHST- 2014/02/24 00:00 [received]
PHST- 2014/03/29 00:00 [revised]
PHST- 2014/03/29 00:00 [accepted]
PHST- 2014/05/06 06:00 [entrez]
PHST- 2014/05/06 06:00 [pubmed]
PHST- 2015/10/01 06:00 [medline]
AID - S0968-0896(14)00241-7 [pii]
AID - 10.1016/j.bmc.2014.03.045 [doi]
PST - ppublish
SO  - Bioorg Med Chem. 2014 Jun 15;22(12):3213-9. doi: 10.1016/j.bmc.2014.03.045. Epub 
      2014 Apr 13.