Studies On The Secondary Metabolites Of Three Marine-derived Actinomycetes

Natural products with novel structure and distinct biological activity are an important resource to the synthetic drugs.Marine-derived actinomycete microbes possess metabolic capabilities different from those of terrestrial actinomycete microbes,which were obtained during their evolution in the marine environment with high-pressure,high salinity,low temperature,low nutrient,resulting in the distinct peculiarity and wide diversity of their metabolites in chemical structure and biological activity.Numcrous natural products with novel structure and distinct biological activity have been discovered from the secondary metabolites of marine-derived actinomycete microbes.These bioactive compounds provided much valuable leading compounds for new drug development,and some of them even have been being in a stage of product development.Therefore,it has great value to do the exploration of marine-derived actinomycete microbes.In order to explore novel natural products from marine-derived actinomycete microbes,liquid partition,RP-18,TLC,NMR,Ms were used in one Streptomyces sp.and two Nonomuraeas sp.Totally,thirty seven compounds were obtained,including ten new compounds.Twenty one compounds were isolated and identified from marine Streptomyces sp.h-119 that was cultured on reformed-G,and PDA agar medium,including two benzoic acid derivatives(P-1,P-8),eleven Cycloheximide derivatives(h-119-7,h-119-13,h-119-14,h-119-22,h-119-24,P-6,P-36,P-38,P-39,P-41,P-42),and one pentanedioic acid derivative(h-119-11).Among them,h-119-3,h-119-7,h-119-11,h-119-14,h-119-22,h-119-24,P-1,P-36,P-41 and P-42 were new compounds.Ten compounds were isolated and identified from marine Nonomuraea sp.5-86 that was cultured on SYP and YMG agar medium,including four cyclic dipeptides(5-86-6,5-86-7,5-86-9,5-86-10),one phthalate derivative(5-86-2),one furancarboxylic acid(5-86-3),one phenylalanine(5-86-5),one indole acid(5-86-11),one pyridine acid(5-86-12)and one terrein(5-86-14).Six compounds were isolated and identified from marine Nonomuraea sp.5-19-1 that was cultured on SYP agar medium,including four cyclic dipeptides(5-19-8,5-19-9,5-19-12,5-19-13),one benzoic acid derivative(5-19-1)and one phenylalanine derivative(5-19-6).The antimicrobial and antitumor in vitro activities of several compounds were assayed by paper disk diffusion method and MTT method respectively.The results showed that compound P-13 inhibited the growth of Staphlococcus aureus CMCC26003,and P-38 inhibited the growth of Colletotrichum gleosporioides Penz.No compounds showed antitumor activities.TLC-bioautography and microplate reader were used for the detection of antioxidant,acetylcholinesterase and tyrosine kinase inhibitors.Most Compounds showed antioxidative activity by scavenging DPPH,while not as good as BHA.No acetylcholinesterase or tyrosine kinase inhibitor was found from the all detected compounds.The results indicated that marine-derived acetinomycete microbes can produce novel metabolites.They are important sources of searching leader compounds for drug discovery.