Bromotyrosine Alkaloids with Acetylcholinesterase Inhibitory Activity from the Thai Sponge Acanthodendrilla sp.

摘要

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 dicbroism data. The complete H-1 and C-13 NMR. assignments of 5,7 beta-dichlorocavemicolin (19) and 5,7 alpha-dichlorocavemicolin (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 IC(50)s of 4.5 and 47.5 mu M, respectively. The hrAChE inhibition kinetics of 7, the most potent alkaloid, showed increased K-m and unchanged V-max values, 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.