Bioactive Aromatic Metabolites from the Sea Urchin-Derived Actinomycete Streptomyces Spectabilis Strain HDa1

An actinomycete strain HDa1, capable of producing new acetylcholinesterase (AchE) inhibitors, was isolated from the gut of sea urchin Anthocidaris crassispina and identified as Streptomyces spectabilis by morphology and 16S rRNA gene sequence. Chemical investigation of the fermentation broth of Streptomyces spectabilis HDa1 by bioactivity-guided fractionation led to the isolation of 3,4-dimethoxy-1-naphthamide (1), p-O-(3,3-dimethylallyl)- benzamide (2), cyclo-(L-Val-L-Pro) (3), cyclo-(L-Ile-L-Pro) (4) and cyclo-(L-Leu-L-Pro) (5). Their structures were determined by analysis of the high-resolution electrospray ionization mass spectrum (HRESIMS), one-dimension (H-1-, C-13 NMR) and two-dimension NMR experiments (HSQC, HMBC and H-1-H-1 COSY), as well as by comparison with those data of known compounds. Compound 1 was identified as a new compound and compound 2 was discovered as a microbial natural product for the first time. All of these isolated compounds were evaluated for acetylcholinesterase inhibitory activity, with compounds 1 and 2 displaying in vitro inhibitory activity against AChE with the inhibition percentage of 54.8% and 43.5%, respectively, at the concentration of 100 mu M. These two natural AChE inhibitors may provide a new chance for drug development for the treatment of neural degeneration disease.