Four novel compounds, chaephilone C (1), chaetoviridides A–C (2–4), were obtained from the culture of a deep sea derived fungus Chaetomium sp. NA-S01-R1, together with four known compounds—chaetoviridin A (5), chaetoviridine E (6), chaetomugilin D (7) and cochliodone A (8). Their structures, including absolute configurations, were assigned based on NMR, MS and time-dependent density functional theory (TD-DFT) ECD calculations. A plausible biogenetic pathway for compounds 1–3 was proposed. Compounds 2 and 3 exhibited antibacterial activities against Vibrio rotiferianus and Vibrio vulnificus. Compounds 1, 3 and 4 displayed similar anti-methicillin resistant Staphylococcus aureus (anti-MRSA) activities in comparison to chloramphenicol. Compound 2 showed the most potent cytotoxic activities towards the Hep G2 cell and compounds 1 and 3 demonstrated relatively stronger cytotoxic activities than the other compounds against the HeLa cell.

Histone deacetylases (HDACs) are major epigenetic modulators involved in a broad spectrum of human diseases including cancers. As HDACs are promising targets of cancer therapy, it is important to understand the mechanisms of HDAC regulation. In this study, we show that ubiquitin-specific peptidase 4 (USP4) interacts directly with and deubiquitinates HDAC2, leading to the stabilization of HDAC2. Accumulation of HDAC2 in USP4-overexpression cells leads to compromised p53 acetylation as well as crippled p53 transcriptional activation, accumulation and apoptotic response upon DNA damage. Moreover, USP4 targets HDAC2 to downregulate tumor necrosis factor TNFα-induced nuclear factor (NF)-κB activation. Taken together, our study provides a novel insight into the ubiquitination and stability of HDAC2 and uncovers a previously unknown function of USP4 in cancers.

A novel anthraquinone, 2-(dimethoxymethyl)-1-hydroxyanthracene-9,10-dione (1), together with nine known compounds (2–10), were isolated from the fermentation of Aspergillus versicolor derived from deep sea sediment. Their structures were established through spectroscopic methods. Compound 1 exhibited strong inhibitory activities against MRSA ATCC 43300 and MRSA CGMCC 1.12409 (with MIC values of 3.9 and 7.8 μg/mL respectively) and moderate activities against tested strains of Vibrio (with MIC values ranging from 15.6 to 62.5 μg/mL). Compound 1 was subjected to molecular docking studies for inhibition of topoisomerase IV and AmpC β-lactamase enzymes indicating its usefulness as antimicrobial agent.

Three novel compounds, 4-methyl-candidusin A (1), aspetritone A (2) and aspetritone B (3), were obtained from the culture of a coral-derived fungus Aspergillus tritici SP2-8-1, together with fifteen known compounds (4–18). Their structures, including absolute configurations, were assigned based on NMR, MS, and time-dependent density functional theory (TD-DFT) ECD calculations. Compounds 2 and 5 exhibited better activities against methicillin-resistant strains of S. aureus (MRSA) ATCC 43300 and MRSA CGMCC 1.12409 than the positive control chloramphenicol. Compound 5 displayed stronger anti-MRSA and lower cytotoxic activities than 2, and showed stronger antibacterial activities against strains of Vibrio vulnificus, Vibrio rotiferianus, and Vibrio campbellii than the other compounds. Compounds 2 and 10 exhibited significantly stronger cytotoxic activities against human cancer cell lines HeLa, A549, and Hep G2 than the other compounds. Preliminary structure–activity relationship studies indicated that prenylation of terphenyllin or candidusin and the tetrahydrobenzene moiety in anthraquinone derivatives may influence their bioactivity.

A novel xanthone dimer derivative, garmoxanthone (1), together with 10 known compounds (2–11), were isolated from bark of Garcinia mangostana. Their structures were established through spectroscopic methods. Garmoxanthone exhibited strong inhibitory activities against MRSA ATCC 43300 and MRSA CGMCC 1.12409 (with MIC values of both 3.9 μg/mL) and moderate activities against tested strains of Vibrio (with MIC values ranging from 15.6 to 31.2 μg/mL). Garmoxanthone is a unique xanthone dimer with linkage of a fused 5/6 ring system and its absolute configuration was elucidated on the basis of experimental and calculated electronic circular dichroism. Garmoxanthone exhibited strong antibacterial activity which partially validated the ethnobotanical use of G. mangostana in the treatment of infections.