Polyketides with potential bioactivities from the mangrove‑derived fungus Talaromyces sp.WHUF0362

Metabolites of microorganisms have long been considered as potential sources for drug discovery.In this study,fve new depsidone derivatives,talaronins A-E(1-5)and three new xanthone derivatives,talaronins F-H(6-8),together with 16 known compounds(9-24),were isolated from the ethyl acetate extract of the mangrove-derived fungus Talaromyces species WHUF0362.The structures were elucidated by analysis of spectroscopic data and chemical methods including alkaline hydrolysis and Mosher’s method.Compounds 1 and 2 each attached a dimethyl acetal group at the aromatic ring.A putative biogenetic relationship of the isolated metabolites was presented and suggested that the depsidones and the xanthones probably had the same biosynthetic precursors such as chrysophanol or rheochrysidin.The antimicrobial activity assay indicated that compounds 5,9,10,and 14 showed potent activity against Helicobacter pylori with minimum inhibitory concentration(MIC)values in the range of 2.42-36.04μmol/L.While secalonic acid D(19)demonstrated signifcant antimicrobial activity against four strains of H.pylori with MIC values in the range of 0.20 to 1.57μmol/L.Furthermore,secalonic acid D(19)exhibited cytotoxicity against cancer cell lines Bel-7402 and HCT-116 with IC_(50) values of 0.15 and 0.19μmol/L,respectively.The structure–activity relationship of depsidone derivatives revealed that the presence of the lactone ring and the hydroxyl at C-10 was crucial to the antimicrobial activity against H.pylori.The depsidone derivatives are promising leads to inhibit H.pylori and provide an avenue for further development of novel antibiotics.

Schiff-base silver nanocomplexes formation on natural biopolymer coated mesoporous silica contributed to the improved curative effect on infectious microbes

Infectious microbes that spread easily in healthcare facilities remain as the severe threat for the public health,especially among immunocompromised populations.Given the intricate problem of dramatic increase in resistance to common biocides,the development of safe and efficient biocide formulated agents to alleviate drug resistance is highly demanding.In this study,Schiff-base ligands were successfully formed on natural biopolymer of epsilon-poly-L-lysine(ε-PL)decorated aldehyde functionalized mesoporous silica SBA-15(CHO-SBA-15)for the selective coordination of silver ions,which was affirmed by various physicochemical methods.Besides the identified broad-spectrum antibacterial activities,the as-prepared Schiff-base silver nanocomplex(CHO-SBA-15/ε-PL/Ag,CLA-1)exhibited an improved inhibitory effect on infectious pathogen growth typified by Escherichia coli and Staphylococcus aureus in comparison with two control silver complexes without Schiff-base conjugates,SBA-15/ε-PL/Ag and CHO-SBA-15/Ag,respectively.In addition,CLA-1 remarkably inhibited the growth of Mycobacterium tuberculosis due to the excellent antimicrobial activity of silver species.Significantly,CLA-1 kills Candida albicans cells,inhibits biofilm formation,and eliminates preformed biofilms,with no development of resistance during continuous serial passaging.The antifungal activity is connected to disruption of bacterial cell membranes and increased levels of intracellular reactive oxygen species.In mouse models of multidrug-resistant C.albicans infection,CLA-1 exhibited efficient in vivo fungicidal efficacy superior to two antifungal drugs,amphotericin B and fluconazole.Moreover,CLA-1 treatment induces negligible toxicity against normal tissues with safety.Therefore,this study reveals the pivotal role of the molecular design of Schiff-base silver nanocomplex formation on biopolymer surface-functionalized silica mesopores as a green and efficient nanoplatform to tackle infectious microbes.