| The challenge of natural product chemistry research is focused on accelerating the discovery of drug lead compounds.In recent years,people have gradually realized that they are coexist for the opportunities and challenge of natural product chemistry in present.Throughout the history of human development,human instincts for the direct or indirect use of natural resources have long been cherished in the development of human civilization for thousands of years.It is necessary to establish natural product database that are compatible with high-throughput screening,including chemical information,biological information,and resource information,owing to the lack of natural producta resources and material or limited by raditional plant resources,and involving novel structure of natural products with higher probability and activity,and potential for new mechanisms such as insects or amphibians and reptiles.In the study of chemical composition,through the recognition of novel compounds and active ingredients in rare resource.Research on the natural product chemistry of rare resourcesat the same time,it is also necessary to select the key scientific issues in each research phase with emphasis and make full use of modern scientific and technological means by multidisciplinary cross.Based on the antibacterial chemistry of arthropods from Pheretima asperfillm E.Perrier and Buthus martensi karsch in this investigation,we explore the mechanism active machnism of natural products,which it will play different roles with macromolecules in the unit cells of living organisms.This will help to advance the study of chemical and chemical biology of Natural products area.Research methods for the isolation and extraction of the secondary metabolites using insects or arthropods,combined with the establishment of in vitro antimicrobial susceptibility assays and improved bactericidal screening techniques,established a set of highly efficient and traces of natural product isolation and identification activities in this laboratory.Effectively evaluate insect and animal-derived natural products with antibiotic-like effects that will provide scientific data and chemical biologic information for new antibiotic-like lead compounds.The results of the study led to the isolation of 10 compounds.Seven of them are new compounds and three known compounds.Nomenclature as(+)5S-methyl,2S-(N-methylpyrrolidine)-propionic acid(compound1);(-)-5,7,22-trienyl-1?,3?,20?-Trihydroxy9?,11?-epoxyergosterol(Compound 2);(-)-1?,3?,20?-trihydroxy-ergosterol-5-ene(Compound 3);(-)-6'''-O-?-D-glucopyranosyl-(1?6''')-[?-D-glucopyranosyl-(1'?6)-indole-D-glucopyranosyl--(1'' ? 4')-D-D-glucopyranosyl]-methylene-3'''-N-thiazolone(compound 4),adenylic acid(compound 5),and thymine(Compound 6),(-)4-(2'-isooctanoic acid)-6-hydroxy-1-methylcyclohexene(Compound 7),(-)-4,22(23)-dien-25-ol-cholestrone-3(compound 8),(-)5(6),22(23)-cholestadiene-3 ?-acetoxy ester(compound 9)and known compound Propylenediamine(compound 10).respedtively,Further research was conducted on the antibacterial activity and bactericidal activity from new compounds.Compounds 3 and 9 were found to have high antibacterial effects.Compound 9 showed a minimum inhibitory concentration of 16 ?g/m L against Pseudomonas aeruginosa,the minimum inhibitory concentration of 16 ?g/mL against Staphylococcus aureus,and the 78 ?g/m L minimum inhibitory concentration against Bacillus subtilis.Compound 9 therefore has broad-spectrum antibacterial activity;Compound 3 has a minimum inhibitoryconcentration of 32 ?g/mL against P.aeruginosa.Based on the above-mentioneddetermination of the MIC value of the antibacterial minimum inhibitory concentration,a compound having a strong antibacterial effect was selected to further determine the minimum bactericidal concentration MBC value,and an antibiotic-like compound component was found.The results showed that the MBC value of compound 9 against the Gram-positive bacterium S.aureus was 32 ?g/mL,and the MBC value against the gram-negative bacterium Pseudomonas aeruginosa was 64 ?g/mL.The MBC value of Compound 3 against Gram-negative P.aeruginosa was 78 ?g/m L.Activity evaluation of trace natural compounds use as a technical innovation in the laboratory for the first time,according to the the drug sensitivity multiple dilution method for a rapid method.The experimental results of this study resul ted in the isolation of two novel structures from arthropods.Both compound 9 and compound 3 of the Gram-negative bacterium P.aeruginosa were the first active compounds discovered,of which compound 9 was found to be derived from a Buthus martensi karsch and compound 3 was found to be from a Pheretima asperfillm E.Perrier.Their structure was identified as a new antibiotic lead compound and is an important innovation in this study.Another important contribution to chemical biology in research is the precise determination and application of stereochemistry circular dichroism in the study of natural products,providing reliable evidence and important parameters for the resolution of the absolute configuration of drug lead compounds.This work was supported by National Natural Science Foundation of China under Grant(No.21472035).The research content is the original innovation research of new structures discovery of natural products,including the chemistry and biological information of two new lead compounds... |
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