title: Synthesis and acetylcholinesterase inhibitory activity of Mannich base derivatives flavokawain B.
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.
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China.
authors.forename: Hao-Ran
authors.initials: HR
authors.lastname: Liu
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China.
authors.forename: Xue-Qin
authors.initials: XQ
authors.lastname: Huang
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China.
authors.forename: Ding-Hui
authors.initials: DH
authors.lastname: Lou
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China.
authors.forename: Xian-Jun
authors.initials: XJ
authors.lastname: Liu
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China.
authors.forename: Wu-Kun
authors.initials: WK
authors.lastname: Liu
authors.affiliation: College of Chemistry and Chemical Engineering, Hunan University, Changsha 410082, China. Electronic address: wangqa@hnu.edu.cn.
authors.forename: Qiu-An
authors.initials: QA
authors.lastname: Wang
mesh_terms: D000110:Acetylcholinesterase / Q000378:metabolism*; D002800:Cholinesterase Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D008352:Mannich Bases / Q000737:chemistry; D008958:Models, Molecular; D015394:Molecular Structure; D013329:Structure-Activity Relationship
chemical_list: D002800:Cholinesterase Inhibitors; D005419:Flavonoids; D008352:Mannich Bases; C452039:flavokawain B; D000110:Acetylcholinesterase
keywords: AChE inhibitory activity; Chalcone Mannich bases; Flavokawain B; Synthesis