Study On Secondary Metabolites And Its Bioactivities Of Two Strains Of Microorganism From Beibu Gulf

Beibu Gulf is one of the most biologically diverse sea area in China.It contains a large number of microbial resources and has become a potential source of new drug research and development.The secondary metabolites of microorganisms in this area are rich,and have novel structures as well as good biological activities.They have good development prospects on the scientific research road of exploring novel structural drug lead compounds.Searching for novel promising drug leads,this paper focuses on microorganisms in the Beibu Gulf.On the basis of TLC and HPLC chemical screen assays and biological activities screening,the mangrove soil-derived actinomycete and the sponge-associated fungus were selected as the objects of this paper.Large-scale fermentations of two strains were implemented.By separating the crude extact with various column chromatographies and semi-prepapative HPLC,fifty monomer compounds were obtained.The structures of all compounds were determined by NMR（1D/2D）,MS,optical ratation,UV,and literature.There were seven new compounds whose absolute configurations were confirmed by the X-ray single crystal diffraction and circular dichroism（CD）analyses.After fermentation actinomyces Streptomyces sp.SCSIO 41400 on the culture medium with soybean powder as nitrogen source,twenty compounds were isolated comprising one new cyclic dipeptide（1）,three known enterotoxins compounds with more complex structure（2–4）,and other sixteen known compounds（5–20）.Among them,compound 1 showed pancreatic lipase（PL）inhibitory activity with IC₅₀ value of27.30μg/m L,and the known compound 9 displayed inhibition against Methicillin-resistant Straphyloccocus aures with MIC value of 12.5μg/m L.Thirty compounds were isolated from the sponge-associated fungus Penicillium sp.SCSIO 41303,including five new N-Methyl-4-quinolones（21–24）and one new citrinin dimer（30）.Compound 21 is a pair of enantiomers,which was further separated into 21a and 21b by chiral resolution.Among them,compounds 22 and 31 exhibited enzyme inhibition activity against PL with IC₅₀ values of 24.62 and 7.16μg/m L,respectively.And compound 31 showed enzyme inhibition activities against acetylcholinesterase（Ach E）with IC₅₀ value of 16.53μg/m L.In summary,seven new compounds were isolated from two microorganisms from Beibu Gulf,and some compounds showed good biological activities,which enriched the structural types of natural products from Beibu Gulf.These findings provide important material foundations and scientific basis for the further development and utilization of microbial resources in the Beibu Gulf,as well as the reaseach and development of new drugs from marine sources.