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Bioorg Med Chem Lett. 2014 Oct 1;24(19):4749-4753. doi: 10.1016/j.bmcl.2014.07.087. Epub 2014 Aug 27.

Synthesis and acetylcholinesterase inhibitory activity of Mannich base derivatives flavokawain B.

Author information

1
College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China.
2
College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China. Electronic address: wangqa@hnu.edu.cn.

Abstract

A novel series of flavokawain B derivatives, chalcone Mannich bases (4-10) were designed, synthesized, characterized, and evaluated for the inhibition activity against acetylcholinesterase (AChE). Biological results revealed that four compounds displayed potent activities against AChE with IC50 values below 20μM. Moreover, the most promising compound 8 was 2-fold more active than rivastigmine, a well-known AChE inhibitor. The logP values of 4-10 were around 2 which indicated that they were sufficiently lipophilic to pass blood brain barriers in vivo. Enzyme kinetic study suggested that the inhibition mechanism of compound 8 was a mixed-type inhibition. Meanwhile, the molecular docking showed that this compound can both bind with the catalytic site and the periphery of AChE.

KEYWORDS:

AChE inhibitory activity; Chalcone Mannich bases; Flavokawain B; Synthesis

PMID:
25205193
DOI:
10.1016/j.bmcl.2014.07.087
[Indexed for MEDLINE]

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