Researches On The Secondary Metabolites And Their Bioactivities From Starfish-Derived Fungus Penicllium Sp.

Owing to the special living environment,with immense genome bank and complex genetic background,marine fungi could product the natural products diverse natural products in structure and activity.Thus,it becomes an important source of the natural products of marine microorganisms.Under the guidance of OSMAC strategy and GNPs technology,the secondary metabolites of ethyl acetate in the Zhen 1,Bean and D media of Penicillium sp.GGF16-1-2 were studied.The structures of 26 compounds were determined by spectroscopic analysis including IR,UV,NMR,HRMS,ORD,CD,XRD and by comparison with the literature.Including 13 dimeric citrinins,which were identified as:penicilloneine A(P-1),penicilloneine B(P-2),penicilloneine C(P-3),dicitrinone E(P-4),dicitrinone F(P-5),dicitrinone G(P-6),dicitrinone H(P-7),penicillone E(P-8),dicitrinin B(P-9),dicitrinin C(P-10),citrinin H1(P-11),penidicitrinin B(P-12),penicitrinone A(P-13);10 monomeric citrinins:penicilliode A(P-14),penicilliode E(P-15),penicilliode D(P-16),citrinin(P-17),dihydrocitrinone(P-18),stoloniferol B(P-19),sclerotinin A(P-20),decarboxydihydrocitrinone(P-21),(1S,3R,4S)-1-(4’-hydroxyl-phenyl)-3,4-dihydro-3,4,5-trimethyl-1H-2-benzopyran-6,8-diol(P-22),phenol A(P-23);3 polyketide compounds:β-diversonolic ester(P-24),sydowinin A(P-25),together with ω-hydroxyemodin(P-26).Compounds P-1～P-8 and P-14～P-16 were new products.Compounds P-1～P-3 were the rare novel quinolone-citrinin dimers in nature,P-4～P-7 were new 7,7’-carbon bridged citrinin dimer,P-8 was first 8,8’-carbon bridged citrinin dimer,and its possible biogenic synthesis was deduced.P-14～P-16 were a new monomer derivative of citrinin.Single crystal data of P-3 and P-14 are obtained for the first time.P-9 was isolated from marine microorganisms for the first time.Their bioactivities were preliminarily evaluated,and the results demonstrated that compounds P-1,P-7,P-9 and P-10 had no antibacterial activities against Staphylococcus aureus and Streptococcus viridan but displayed potential antibacterial activities against Colletotrichum gloeosporioides,with LC50 of 0.02,9.63,8.87 and 0.61 μg/mL,respectively.P-14 showed no inhibitories to Staphyloc-occus epidermidis,Staphylococcus aureus,methicillin-resistant Staphylococcus aureus,Escherichia coli and Pseudomonas aeruginosa.The preliminary screening results of anti-inflammatory activity in vitro showed that at the concentration of 100 μM,P-9 and P-10 could significantly inhibit the production of IL-1β、IL-6 and TNF-α in LPS-treated RAW246.7cells,and enhanced the production of IL-4 and IL-13 anti-inflammatory cytokines,which means P-9 and P-10 have anti-inflammatory effect.However,P-1 and P-7 have no obvious anti-inflammatory effect.They showed no insecticidal activity to diamondback moth larvae(Plutella xylostella L.).