Synthesis and Anticholinesterase Activity of (-)-Physostigmine Analogues with Modifications at C3a and C5

doi:10.1007/s40242-013-3066-y

Chemical Research in Chinese Universities ›› 2013, Vol. 29 ›› Issue (5): 888-893.doi: 10.1007/s40242-013-3066-y

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Synthesis and Anticholinesterase Activity of (-)-Physostigmine Analogues with Modifications at C3a and C5

WANG Hui-jing¹, ZHANG Dan¹, WANG Fu-sheng², WU Yi², SONG Hao²

1. Innovative Drug Research Center, Chongqing University, Chongqing 401331, P. R. China;
2. Key Laboratory of Drug Targeting and Novel Delivery System of the Ministry of Education, West China School of Pharmacy, Sichuan University, Chengdu 610041, P. R. China

Received:2013-02-22 Revised:2013-05-15 Online:2013-10-01 Published:2013-09-17
Contact: ZHANG Dan E-mail:danzhang@cqu.edu.cn
Supported by:
Supported by the National Natural Science Foundation of China(No.21202209), the National Science & Technology Major Project of China(No.2011ZX09401-304), the Fundamental Research Funds for the Central Universities, China (No.CQDXWL-2012-131) and the Natural Science Foundation Project of Chongqing Science and Technology Commission, China(No.cstc2012jjA10087).

Abstract

Abstract:

A new series of physostigmine analogues 3a―3j with modifications at the C3a and C5 positions was designed and synthesized. Bioassay of the synthetic analogues 3a―3j, along with the previous synthesized C3a-ethyl-C5-triazole physostigmine analogues 1a―1g and 2a―2j was performed, which indicates that the replacement of the carbamoyl moiety of C3a-ethyl-C5-triazole analogues 1 and 2 with a triazole moiety decreased acetylcholinesterase(AchE) inhibitory activity, whereas the introduction of heterocycles into the triazole ring increased both AChE and butyrylcholinesterase(BchE) inhibitory activities. Structure-activity relationship(SAR) studies of C3a-methyl-C5-triazole analogues 3 reveal the C3a-methyl substituent is important for AChE and BChE inhibition and the introduction of a second ionizable N center improved the binding of the synthetic analogues to both AChE and BChE.

Key words: C3a-ethyl-C5-triazole physostigmine analogue, C3a-methyl-C5-triazole physostigmine analogue, Anti-cholinesterase activity, Alzheimer’s disease

WANG Hui-jing, ZHANG Dan, WANG Fu-sheng, WU Yi, SONG Hao. Synthesis and Anticholinesterase Activity of (-)-Physostigmine Analogues with Modifications at C3a and C5[J]. Chemical Research in Chinese Universities, 2013, 29(5): 888-893.

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Synthesis and Anticholinesterase Activity of (-)-Physostigmine Analogues with Modifications at C3a and C5

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