Design, synthesis and evaluation of isaindigotone derivatives as acetylcholinesterase and butyrylcholinesterase inhibitors.
A series of isaindigotone derivatives 5a-d and 6a-d were designed, synthesized and evaluated as acetylcholinesterase and butyrylcholinesterase inhibitors. Results showed that the novel class of isaindigotone derivatives could inhibit both cholinesterases and the selectivity of AChE over BuChE inhibition was related to the aromatic, the species and length of the alkyl amino side chain of compounds. The structure-activity relationships were discussed and their multiple binding modes were further clarified in the molecular docking studies.
Pan
Li
L
School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510080, People's Republic of China.
Tan
Jia-Heng
JH
Hou
Jin-Qiang
JQ
Huang
Shi-Liang
SL
Gu
Lian-Quan
LQ
Huang
Zhi-Shu
ZS
D000110:Acetylcholinesterase / Q000737:chemistry*; D000470:Alkaloids / Q000138:chemical synthesis* / Q000737:chemistry; D001665:Binding Sites; D002091:Butyrylcholinesterase / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008956:Models, Chemical; D008968:Molecular Conformation; D015394:Molecular Structure; D011799:Quinazolines / Q000138:chemical synthesis* / Q000737:chemistry; D013329:Structure-Activity Relationship
D000470:Alkaloids; D002800:Cholinesterase Inhibitors; D004791:Enzyme Inhibitors; D011799:Quinazolines; C440668:isaindigotone; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase