Synthesis of physostigmine analogues and evaluation of their anticholinesterase activities.
A series of physostigmine analogues were prepared and evaluated for cholinesterase inhibition activities, including acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). Most of them showed potent inhibition activities against AChE, in which compound 17 especially exhibited significantly higher selectivity over BChE than phenserine, a compound currently on clinical trial. Discussion about the relationships between structure and activity of these derivatives was also presented.
Zhan
Zha-Jun
ZJ
College of Pharmaceutical Science, Zhejiang University of Technology, Hangzhou 310014, PR China.
Bian
Hong-Ling
HL
Wang
Jian-Wei
JW
Shan
Wei-Guang
WG
D000110:Acetylcholinesterase / Q000737:chemistry* / Q000378:metabolism; D000818:Animals; D002091:Butyrylcholinesterase / Q000737:chemistry* / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010830:Physostigmine / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D013329:Structure-Activity Relationship
D002800:Cholinesterase Inhibitors; D007211:Indoles; D018377:Neurotransmitter Agents; D010830:Physostigmine; D000110:Acetylcholinesterase; D002091:Butyrylcholinesterase; C092280:phenserine