Synthesis and biological evaluation of 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives as dual binding site acetylcholinesterase inhibitors.
A series of 7H-thiazolo[3,2-b]-1,2,4-triazin-7-one derivatives 7a-i were synthesized and evaluated as novel acetylcholinesterase (AChE) inhibitors. All target compounds were evaluated in vitro for the inhibitory activities against AChE via Ellman colorimetric assay. Compound 7c showed an excellent (89.82%) inhibitory activity. The molecular docking studies revealed that 7c, 7d and 7g, with the lateral chain in the para position of the phenyl ring, possessed an optimal docking pose and can perfectly fit into the catalytic active site (CAS) and peripheral anionic site (PAS), simultaneously, and, consequently, exhibited higher inhibitory potency than 7b that bears the same lateral chain as 7g, but in the ortho position of the phenyl ring.
College of Chemical Engineering, Shijiazhuang University, 6 Changjiang Road, New Technology Development District, Shijiazhuang 050035, PR China. Electronic address: liusijie1982@163.com.
Sijie
S
Liu
Key Laboratory of New Animal Drug Project of Gansu Province, Key Laboratory of Veterinary Pharmaceutical Development, Ministry of Agriculture, Lanzhou Institute of Husbandry and Pharmaceutical Sciences of CAAS, Lanzhou, PR China, China. Electronic address: shangrf1974@163.com.
Ruofeng
R
Shang
College of Chemical Engineering, Shijiazhuang University, 6 Changjiang Road, New Technology Development District, Shijiazhuang 050035, PR China.
Lanxiang
L
Shi
Department of Biochemistry, The Chinese University of Hong Kong, Hong Kong SAR, China.
David Chi-Cheong
DC
Wan
Department of Biochemistry, The Chinese University of Hong Kong, Hong Kong SAR, China.
Huangquan
H
Lin
D000110:Acetylcholinesterase / Q000378:metabolism*; D001665:Binding Sites / Q000187:drug effects; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014227:Triazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*
C000595940:7H-thiazolo(3,2-b)-1,2,4-triazin-7-one; D002800:Cholinesterase Inhibitors; D013844:Thiazoles; D014227:Triazines; D000110:Acetylcholinesterase
Acetylcholinesterase; Alzheimer's disease; Docking; Inhibitors; Synthesis