title: Inhibition of cholinesterase and monoamine oxidase-B activity by Tacrine-Homoisoflavonoid hybrids.
abstract: A series of Tacrine-Homoisoflavonoid hybrids were designed, synthesised and evaluated as inhibitors of cholinesterases (ChEs) and human monoamine oxidases (MAOs). Most of the compounds were found to be potent against both ChEs and MAO-B. Among these hybrids, compound 8b, with a 6 carbon linker between tacrine and (E)-7-hydroxy-3-(4-methoxybenzylidene)chroman-4-one, proved to be the most potent against AChE and MAO-B with IC50 values of 67.9 nM and 0.401 μM, respectively. This compound was observed to cross the blood-brain barrier (BBB) in a parallel artificial membrane permeation assay for the BBB (PAMPA-BBB). The results indicated that compound 8b is an excellent multifunctional promising compound for development of novel drugs for Alzheimer's disease (AD).
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, China.
authors.forename: Yang
authors.initials: Y
authors.lastname: Sun
authors.forename: Jianwen
authors.initials: J
authors.lastname: Chen
authors.forename: Xuemin
authors.initials: X
authors.lastname: Chen
authors.forename: Ling
authors.initials: L
authors.lastname: Huang
authors.forename: Xingshu
authors.initials: X
authors.lastname: Li
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology; D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism; D002800:Cholinesterase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D002802:Cholinesterases / Q000378:metabolism*; D004593:Electrophorus; D006801:Humans; D007529:Isoflavones / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D008995:Monoamine Oxidase / Q000378:metabolism*; D008996:Monoamine Oxidase Inhibitors / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*; D013552:Swine; D013619:Tacrine / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology*
chemical_list: D002800:Cholinesterase Inhibitors; D007529:Isoflavones; D008996:Monoamine Oxidase Inhibitors; D013619:Tacrine; D008995:Monoamine Oxidase; D002802:Cholinesterases
keywords: Alzheimer’s disease; Cholinesterase; Monoamine oxidase-B