title: Bromotyrosine Alkaloids with Acetylcholinesterase Inhibitory Activity from the Thai Sponge Acanthodendrilla sp.
abstract: Twenty bromotyrosine alkaloids, including a new compound, 13-oxosubereamolline D (5), were isolated from the Thai sponge Acanthodendrilla sp. Their structures were determined by analyses of 1D- and 2D-NMR, high-resolution mass, and circular dichroism data. The complete 1H and 13C NMR assignments of 5,7β-dichlorocavernicolin (19) and 5,7α-dichlorocavernicolin (20) are described herein for the first time. The acetylcholinesterase (AChE) inhibitory activity of all isolated compounds was evaluated. Only homoaerothionin (7) and fistularin 1 (10) exhibited inhibitory activity against human recombinant AChE (hrAChE) with IC50s of 4.5 and 47.5 µM, respectively. The hrAChE inhibition kinetics of 7, the most potent alkaloid, showed increased Km and unchanged Vmaxvalues, suggesting its competitive mode of inhibition. The spirocyclohexadienylisoxazole and the length of the alkyl diamine linkage were proposed as the crucial parts for its strong inhibitory activity. This finding indicates a therapeutic potential for 7 in acetylcholine-related diseases, most importantly Alzheimer's disease.
authors.forename: Natchanun
authors.initials: N
authors.lastname: Sirimangkalakitti
authors.forename: Opeyemi J
authors.initials: OJ
authors.lastname: Olatunji
authors.forename: Kanokwan
authors.initials: K
authors.lastname: Changwichit
authors.forename: Tongchai
authors.initials: T
authors.lastname: Saesong
authors.forename: Supakarn
authors.initials: S
authors.lastname: Chamni
authors.forename: Pithi
authors.initials: P
authors.lastname: Chanvorachote
authors.forename: Kornkanok
authors.initials: K
authors.lastname: Ingkaninan
authors.forename: Anuchit
authors.initials: A
authors.lastname: Plubrukarn
authors.forename: Khanit
authors.initials: K
authors.lastname: Suwanborirux
mesh_terms: D000110:Acetylcholinesterase / Q000032:analysis; D000470:Alkaloids / Q000737:chemistry*; D000818:Animals; D002800:Cholinesterase Inhibitors / Q000737:chemistry*; D006801:Humans; D007700:Kinetics; D015394:Molecular Structure; D011161:Porifera / Q000737:chemistry*; D013785:Thailand; D014443:Tyrosine / Q000031:analogs & derivatives* / Q000737:chemistry
chemical_list: D000470:Alkaloids; D002800:Cholinesterase Inhibitors; C475724:bromotyrosine; D014443:Tyrosine; D000110:Acetylcholinesterase