Study On The Secondary Metabolites And Derivatives Of Streptomyces Cacaoi Subsp.asoensis H₂S₅ From Qingling Mountains

In recent years,drug resistance has been a major problem in clinical medicine.Due to the side effects of chemotherapy drugs and the abuse of antibiotics,a large number of tumor-resistant cell lines and super-resistant bacteria are born in our lives.This phenomenon leads to the gradual reduction of the therapeutic effect of the original specific antibiotics,and many treatment methods have lost their effect.It is urgent to find new active lead compounds.As a gift from nature,natural products with high efficiency and low toxicity have assumed this responsibility.Natural products are derived from the secondary metabolism of organisms and are an important part of biological processes.The main sources of microorganisms are actinomycetes,fungi and bacteria,of which actinomycetes account for 45%.Among actinomycetes,Streptomyces accounted for 90%,which is the main source of microorganisms.Streptomyces is extremely rich in secondary metabolites,including ansamycin compounds.Ansamycin is a class of macrolide antibiotics.Although there are not many types,it has a wide range of activities and a high rate of drug preparation.Its active skeleton is very worthy of attention.In this paper,a strain of Streptomyces sp.H2S5 derived from moss soil in Qinling Mountains was used as the research object.We obtained the crude extract of its secondary metabolites by fermentation and cultivation and used a variety of chromatographic techniques（reversed phase medium pressure preparative chromatography,normal pressure positive and reversed phase Silica gel,dextran gel,high performance liquid chromatography）to extract,separate and purify the fermentation products.Totally,11 ansamycin compounds were identified through multiple spectroscopy and spectroscopy techniques（nuclear magnetic resonance,mass spectrometry,infrared,ultraviolet,and circular dichroism）,including 3 novel compounds:strecacansamycin A（1）,strecacansamycin B（2）,strecacansamycin C（3）and 8 known trienomycins:trienomycin A（4）,trienomycin B（5）,trienomycin C（6）,trienomycin D（7）,trienomycin E（8）,trienomycin G（9）,trienomycin L（10）and trienomycinol（11）.At the same time,the novel compounds were tested for their anti-prostate cancer cell PC-3 activity,anti-hepatoma cell Hep G2 activity,and human malignant glioma cell U87 MG activity.The results show that 2 have a relatively obvious inhibitory effect on Hep G2 with an IC₅₀ value of 0.61μM while for U87-MG with an IC₅₀ value of 7.0μM,which can significantly change cell morphology.Besides,we connected the highlighted compound trienomycin A（1）with a biological probe for deeper protein screening research.Meanwhile,based on the results simulated by the computer,we speculate that changing the carbon atom at position 34 of trienomycin A（1）to nitrogen atom and the hydroxyl group at position20 to methoxy will increase its binding ability with protein.Accordingly,a preli minary study on the synthesis of trienomycins derivatives was initiated.