Study On Ansamycins And The Cytotoxity From Streptomyces Cacao In Qinling

Natural products are secondary metabolites of organisms and important components of biological processes.The chemical diversity of these molecules is enormous,which provides inspiration for innovation in medicine,nutrition,agrochemical research and biology.Ansamycin is a class of macrocyclic steroid antibiotics derived from plants or microorganisms,which possess a wide range of biological activities,such as antiviral,antitumor and antibacterial activities.Although there are few kinds of ansamycin antibiotics,they have a wide range of physiological activities and high drug-forming rates,and thought as a class of active skeletons worthy of attention.In this paper,Streptomyces sp.H2S5,isolated from moss soil collected from Qinling Mountain,was taken as the research object.The fermentation conditions were screened and had obtained a solid medium,which could produce trienomycin A at 8.5 mg/L.Based on the OSMAC strategy,the liquid fermentation conditions of Streptomyces sp.H2S5 were systematically optimized from various medium and culture conditions,the components of the liquid medium were finally determined and large-scale fermentation was carried out.The fermentation cultures of the strains were extracted and purified on the basis of various chromatographic techniques（medium pressure preparative chromatography,high-speed countercurrent chromatography,high-performance liquid chromatography,atmospheric pressure reversed-phase silica gel,dextran gel,etc.）.Ten ansamycins were identified by various spectral techniques（NMR,MS,IR,UV）,including two novelties,tricyclobenzomycin A（2）and（R/S）-trienomycin C（3）;8 trienomycins,including trienomycin A（1）,demethyltrienomycinol（4）,trienomycinol（5）,trienomycin B（6）,trienomycin C（7）,trienomycin D（8）,trienomycin E（9）,trienomycin G（10）.All compounds were tested for cytotoxicity activity against PC-3 and Hep G2,then the structure-activity relationship was briefly discussed.Compounds 1 and 8 showed better cytotoxicity against PC-3 and Hep G2 cells than the positive control,doxorubicin.The IC₅₀values for PC-3 were 0.43μM and 0.7μM,for which Hep G2 were 0.17μM and 0.21μM,respectively.In addition,compounds 2,7 and 9 also showed strong inhibitory effect on Hep G2 cells.This research has unearthed novel ansamycin and found compounds with good inhibitory activity against PC-3 and Hep G2.It has important practical significance for the discovery of new drugs,solving the antibiotic crisis and treating diseases.At the same time,a high-yield trienomycin A medium was screened,which laid a foundation for the analysis of its biosynthetic pathway and the exploitation of novel ansamycins.