Stereostructures And Bioactivities Of Secondary Metabolites From Penicillium Janthinellum And Aspergillus Flavus Collected From The Bohai Sea

Marine-derived fungi have unique metabolic pathways and genetic backgrounds due to their special living environment.Thees metabolites possessed novel structures and unique activities.Numerous studies have showed that the secondary metabolites from marine-derived fungi were abundant,and a series of drugs and lead compounds for the treatment of major human diseases have been discovered from the limitedly studied fungal resources.Among them,marine-derived Penicillium fungi and Aspergillus fungi have been reported as source of many drugs that have been used clinically,such as Penicillin secondary metabolites penicillin,and Aspergillus secondary metabolite mevastatin.Therefore,we selected the fungi of the genus of Penicillium and Aspergillus collected from the Bohai Sea as the research object.The strains were subjected to fermentation,extraction,isolation and purification of secondary metabolites,determination of the structure and configuration of the compounds,and exploration of the biological activity of the compounds.In this study,based on the research methods of marine natural products,a variety of chromatographic separation techniques and modern spectroscopy techniques were combined with quantum chemical calculations to study secondary metabolites of fungi.The isolated compounds were tested for their inhibitory activities against pathogenic bacteria.One Bohai-derived fungus was Aspergillus flavus?07-1?,Gene Bank number is KY979506.13 Compounds?1-13?were obtained from the fungus,of which 1,2,3,and 4were new compounds,and 5 was fusi acids,6-9 were ring-expanding steroids,and 10-13 were ergot derivatives.The activity test showed that compound 5 exhibited a strong inhibitory activity against various pathogenic bacteria.The MICs were?0.07,0.07,0.07,0.3?M?stronger than the positive control drugs,and showed moderate inhibitory activity with IC₅₀values of 36.29,30.14,37.77,38.12,31.28?M,respectively toward to MDA-MB-231,HELA,MGG-803,MCF-7,A549 tumor cell lines.During the separation process,the yield of compound 5 was found to be large,and its activity was better,so its structure was modified and 10 derivatives were obtained.Another Bohai-derived fungus was Penicillium janthinellum?07-5?,Gene Bank number is KY979507.Seventeen monomeric compounds?14-30?were isolated and identified,of which 14 was new compound,15-19 were alkaloids,20-22 were citrinin derivatives,23-26were coumarin derivatives,28 was mixed terpenoid,and 29 was a sesquiterpenoid.Among them,compounds 20 and 22 showed strong antibacterial activity against some pathogenic bacteria,with MICs?0.8,0.4?M?being stronger than the positive control ciprofloxacin.Compound 20 was an citrinin dimer,which was deduced in the previous study using the method of derivation from biological origin.In this study,the structure of compound 20 was analyzed using quantum chemistry calculation combined with CD,and the configuration was analyzed using eight calculation levels and DP4+method to determine the absolute configuration of citrinin dimer?2'R,3'S,3R,4S?,demonstrating the value of quantum chemistry calculations in natural products.In summary,the natural products with good activity were isolated from the Bohai Sea-derived fungi Penicillium janthinellum and Aspergillus flavus.The absolute configuration of the compounds was determined by spectroscopic methods and quantum chemical calculations.Antibacterial activity experiments showed that some of the compounds had good activity against certain pathogenic bacteria,which provided the basis for the development and application of drug lead compounds.