Studies On Antibacterial Ingredients From Marine Fungus Aspergillus Flavipes

In this study,33 strains of marine fungi were isolated from the Dalian offshore mud.Antibacterial activity screened strain DL-11 has a broad spectrum of high-efficiency antibacterial effects,chemical analysis found that its metabolites are abundant.Through morphological observation and ITS sequence analysis,the fungus was identified as Aspergillus flavipes.Using antibacterial activity-chemical analysis-oriented method,comprehensive use of multiple chromatographic-spectroscopy methods to isolate and identify 18 secondary metabolites from the active sites in its large-scale fermentation?1-18?.Among them,11diphenyl ether compounds?1-11?:4'-chloroasterric acid?1?,Methyl chloroasterrate?2?,penicillither?3?,Iizukine A?4?,Asterric acid?5?,Monomethylosoic acid?6?,Butyl 2,4-dichloroasterrate?7?,2,4-dichloroasterric acid?8?,Methyl dichloroasterrate?9?,Geodin hydrate?10?,6'-chloroasterric acid?11?;benzophenones 2?12-13?:Monochlorsulochrin?12?,Dihydrogeodin?13?;xanthones 2?14-15?:Xanthone compounds-carboxylate?14?,Methyl-?4-chloro-l,6-dihydroxy-3-methylxanthone?-8-carboxylate?15?;3 steroids?16-18?;?22E?-5a,8a-Epidioxyergosta-6,22E-dien-3?-ol?16?,?-sitosterol?17?and ergosta-4,6,8?14?,22-tetraen-3-one?18?.Compound 1 is a new compound.The antibacterial activity re-screening test was performed on the monomer compounds whose structure was determined by the micro-dilution method.The results showed that:?1?In vitro antibacterial experiments found that compounds 1-15 showed moderate to strong antibacterial activity against multiple Gram-positive bacteria,with IC₅₀0 values?of3.13-50?g/mL,but not against Gram-negative bacteria V.parahemolyticus ATCC17802Activity(IC₅₀>100?g/mL).?2?Diphenyl ether?1-11?,benzophenone?12-13?and xanthone?14-15?are not sensitive to the antibacterial activity of E.faecalis ATCC51299,except for 7,13 showed weak antibacterial activity(IC₅₀0 value of 12.5?g/mL).?3?4,5,and 7 pairs of E.faecium ATCC35667 showed strong antibacterial activity(IC₅₀values of 3.13,3.13,6.25?g/mL),which were comparable to the positive control drugs.?4?Antibacterial activity of benzophenone and xanthone on 4 strains S.aureus ATCC43300,S.aureus ATCC 29213,S.aureus ATCC 33591,S.aureus ATCC 25923)is generally better than that of diphenyl ethers Compounds have better antibacterial activity than positive drugs.9 showed strong antibacterial activity against S.aureus ATCC 43300(IC₅₀0 value of 3.13?g/mL).In this thesis,18 secondary metabolites were isolated from a marine fungus A.flavipes with antibacterial activity.Among them,15 compounds?1-15?had good antibacterial activity,and some of the active effects were even better than the positive control drug.This research laid the foundation for the research and development of antimicrobial drugs derived from marine microorganisms.