A new sesquiterpenoid 9,10-diolhinokiic acid (1) and a new diterpenoid roussoellol C (2), together with 4 known compounds, were isolated from the extracts of laboratory cultures of marine-derived fungus Talaromyces purpurogenus. 9,10-diolhinokiic acid is the first thujopsene-type sesquiterpenoid containing a 9,10-diol moiety, and roussoellol C possesses a novel tetracyclic fusicoccane framework with an unexpected hydroxyl at C-4. These new structures were confirmed by spectroscopic data, chemical method, NMR data calculations and electronic circular dichroism (ECD) calculations. The selected compounds were evaluated for cytotoxicities against five human cancer cell lines, including SW480, HL-60, A549, MCF-7, and SMMC-7721 and the IC₅₀ values of compound 2 against MCF-7 and 3 against HL-60 cells were 6.5 and 7.9 μM, respectively.

Four naphtho-γ-pyrones (fonsecinones A and C and aurasperones A and E) were identified as potential antibacterial agents againstEscherichia coli, extended-spectrumβ-lactamase (ESBL)-producingE. coli, Pseudomonas aeruginosa, Enterococcus faecalis, and methicillin-resistantStaphylococcus aureus(MRSA) in anin vitroantibacterial screen of 218 fungal metabolites. Fonsecinone A (2) exhibited the most potent antibacterial activity, with minimum inhibitory concentrations (MICs) of 4.26, 17.04, and 4.26 μg/mL against ESBL-producingE. coli, P. aeruginosa, andE. faecalis, respectively. The inhibitory effects of fonsecinones A (2) and C (3) againstE. coliand ESBL-producingE. coliwere comparable to those of amikacin. Molecular docking-based target identification of naphtho-γ-pyrones1–8revealed bacterial enoyl-acyl carrier protein reductase (FabI) as an antibacterial target, which was further validated by FabI affinity and inhibition assays. Fonsecinones A (2) and C (3) and aurasperones A (6) and E (7) bound FabI specifically and produced concentration-dependent inhibition effects. This work is the first report of anti-drug-resistant bacterial activities of naphtho-γ-pyrones1–8and their possible antibacterial mechanism of action and provides an example of the successful application ofin silicomethods for drug target identification and validation and the identification of new lead antibiotic compounds against drug-resistant pathogens.

Two new phenone derivatives penicophenones A (1) and B (2), a new cyclic tetrapeptide penicopeptide A (3) and five known compounds were isolated from the culture broth of Penicillium commune, an endophytic fungus derived from Vitis vinifera. Compounds 1–3 were elucidated by extensive spectroscopic analyses including 1D and 2D NMR and HRESIMS. The absolute configurations of 1 and 3 were determined by comparing its ECD with related molecules and modified Marfey’s analysis, respectively. Penicophenone A (1) possesses a rare benzannulated 6,6-spiroketal moiety, which is a new member of the unusual structural class with peniphenone A as the representative. Compound 3 exhibited significant inhibition activities against 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) in vitro and showed strong binding affinity to 11β-HSD1. Moreover, compound 3 treatments decreased the lipid droplet accumulation associate with the inhibition of 11β-HSD1 expression in differentiate-induced 3T3-L1 preadipocytes. Furthermore, the molecular docking demonstrated that compound 3 coordinated in the active site of 11β-HSD1 is essential for the ability of diminishing the enzyme activity.