Psilostachyin C reduces malignant properties of hepatocellular carcinoma cells by blocking CREBBP-mediated transcription of GATAD2B.

Hepatocellular carcinoma (HCC) is a leading cause of cancer-related mortality globally. Many herbal medicines and their bioactive compounds have shown anti-tumor properties. This study was conducted to examine the effect of psilostachyin C (PSC), a sesquiterpenoid lactone isolated from Artemisia vulgaris L., in the malignant properties of HCC cells. CCK-8, flow cytometry, wound healing, and Transwell assays revealed that 25 µM PSC treatment significantly suppressed proliferation, cell cycle progression, migration, and invasion of two HCC cell lines (Hep 3B and Huh7) while promoting cell apoptosis. Bioinformatics prediction suggests CREB binding protein (CREBBP) as a promising target of PSC. CREBBP activated transcription of GATA zinc finger domain containing 2B (GATAD2B) by binding to its promoter. CREBBP and GATAD2B were highly expressed in clinical HCC tissues and the acquired HCC cell lines, but their expression was reduced by PSC. Either upregulation of CREBBP or GATAD2B restored the malignant properties of HCC cells blocked by PSC. Collectively, this evidence demonstrates that PSC pocessess anti-tumor functions in HCC cells by blocking CREBBP-mediated transcription of GATAD2B.

Production of kojic acid by Aspergillus flavus OL314748 using box-Behnken statistical design and its antibacterial and anticancer applications using molecular docking technique.

Kojic acid is a wonderful fungal secondary metabolite that has several applications in the food, medical, and agriculture sectors. Many human diseases become resistant to normal antibiotics and normal treatments. We need to search for alternative treatment sources and understand their mode of action. Aspergillus flavus ASU45 (OL314748) was isolated from the caraway rhizosphere as a non-aflatoxin producer and identified genetically using 18S rRNA gene sequencing. After applying the Box-Behnken statistical design to maximize KA production, the production raised from 39.96 to 81.59 g/l utilizing (g/l) glucose 150, yeast extract 5, KH2PO4 1, MgSO4.7H2O 2, and medium pH 3 with a coefficient (R2) of 98.45%. Extracted KA was characterized using FTIR, XRD, and a scanning electron microscope. Crystalized KA was an effective antibacterial agent against six human pathogenic bacteria (Bacillus cereus, Staphylococcus aureus, Escherichia coli, Klebsiella pneumonia, Serratia marcescens, and Serratia plymuthica). KA achieves high inhibition activity against Bacillus cereus, K. pneumonia, and S. plymuthica at 100 µg/ml concentration by 2.75, 2.85, and 2.85 compared with chloramphenicol which gives inhibition zones 1, 1.1, and 1.6, respectively. Crystalized KA had anticancer activity versus three types of cancer cell lines (Mcf-7, HepG2, and Huh7) and demonstrated high cytotoxic capabilities on HepG-2 cells that propose strong antitumor potent of KA versus hepatocellular carcinoma. The antibacterial and anticancer modes of action were illustrated using the molecular docking technique. Crystalized kojic acid from a biological source represented a promising microbial metabolite that could be utilized as an alternative antibacterial and anticancer agent effectively.

Development of a water-soluble fluorescent Al3+ probe based on phenylsulfonyl-2-pyrone in biological systems.

BACKGROUND: Al exists naturally in the environment and is an important component in acidic soils, which harm almost all plants. Furthermore, Al is widely used in food additives, cosmetics, and medicines, resulting in living organisms ingesting traces of Al orally or dermally every day. Accordingly, Al accumulates in the body, which can cause negative bioeffects and diseases, and this concern is gaining increasing attention. Therefore, to detect and track Al in the environment and in living organisms, the development of novel Al-selective probes that are water-soluble and exhibit fluorescence at long wavelengths is necessary. RESULTS: In this study, an Al3+-selective fluorescent probe PSP based on a novel pyrone molecule was synthesized and characterized to detect and track Al in biological systems. PSP exhibited fluorescence enhancement at 580 nm in the presence of Al3+ in aqueous media. Binding analysis using Job's plot and structural analysis using 1H NMR showed that PSP formed a 1:1 complex with Al3+ at the two carbonyl groups of the dimethyl malonate of the pyrone ring. Upon testing in biological systems, PSP showed good cell membrane permeability, detected intracellular Al3+ in human breast cancer cells (MDA-MB-231), and successfully imaged accumulated Al3+ in Microcystis aeruginosa and the larvae of Rheocricotopus species. SIGNIFICANCE: The novel Al3+-selective fluorescent probe PSP is highly effective and is expected to aid in elucidating the role of Al3+ in the environment and living organisms.

PBAT/PLA food packaging film containing sodium dehydroacetate-loaded diatomite as an antibacterial agent: Fabrication, water-gas regulation and long-acting antimicrobial mechanism.

Biodegradable food packaging films with good antimicrobial properties are highly sought after for prolonging the shelf-life of fruits and vegetables whilst minimizing waste streams originating from the food sector. In this work, a series of PBAT/PLA food packaging films containing sodium dehydroacetate-loaded diatomite (SD/D) as an antimicrobial agent were fabricated. Structural analyses showed that the sodium dehydroacetate was incorporated into the pores of the diatomite. A uniform dispersion of SD/D in the composite films effectively enhanced water and gas permeability, whilst also giving the films good mechanical properties. The slow release of SD endowed the composite films with long-acting antibacterial ability (>90 % bacteriostasis rate for E. coli and >85 % bacteriostasis rate for S. aureus). The composite films were able to effectively maintain the quality of banana fruits during storage at room temperature, encouraging their use in food applications where non-biodegradable petrochemical-derived packaging films have traditionally been used.

Antinociceptive and anti-inflammatory activity of extracts and α-pyrones isolated from Cantinoa stricta.

This study evaluated the composition and the antinociceptive and anti-inflammatory activity of the crude extracts and two isolated compounds, anamarine (ANA) and 10-epi-olguine (eOL), obtained from the leaves of Cantinoa stricta (Lamiaceae). Crude ethanolic extract (EEt) and dichloromethane extract (DCM), selected based on NMR data, were submitted to pharmacological tests in male Swiss mice. The oral administration of EEt and DCM significantly reduced the second phase of formalin-induced nociception (60%), lipopolysaccharide (LPS)-induced mechanical hyperalgesia (90%), and carrageenan (Cg)-induced edema (25%). ANA and eOL, the major compounds in EEt and DCM extracts, administered orally or locally (in the paw), also reduced the LPS-induced mechanical hyperalgesia (Oral ID50 1.9 and 3.9 mg/kg; Local ID50 93.4 and 677.3 ng, respectively) without changing the thermal acute nociception or the motor performance of the animals. Local administration of ANA and eOL also reduced Cg-induced edema (40 and 23%, respectively). These isolated compounds did not change the mechanical hyperalgesia induced by tumor necrosis factor-α, interleukin-1ß, prostaglandin E2, dibutyryl cyclic AMP, or forskolin but reversed the hyperalgesia induced by dopamine, epinephrine, and phorbol 12-myristate 13-acetate. The hyperalgesia induced by epinephrine was reversed in male but not in female mice, in which this response is not dependent on protein kinase C (PKC). These results suggest that C. stricta extracts possess antinociceptive and anti-inflammatory activity which is related to the presence of ANA and eOL. Differently from the known analgesics, these substances seem to exert their action mainly interfering with the sympathetic component of pain, possibly with PKC.

Novel triterpenoid pyrones, phthalimides and phthalates are selectively cytotoxic in CCRF-CEM cancer cells - Synthesis, potency, and mitochondrial mechanism of action.

A series of triterpenoid pyrones was synthesized and subsequently modified to introduce phthalimide or phthalate moieties into the triterpenoid skeleton. These compounds underwent in vitro cytotoxicity screening, revealing that a subset of six compounds exhibited potent activity, with IC50 values in the low micromolar range. Further biological evaluations, including Annexin V and propidium iodide staining experiment revealed, that all compounds induce selective apoptosis in cancer cells. Measurements of mitochondrial potential, cell cycle analysis, and the expression of pro- and anti-apoptotic proteins confirmed, that apoptosis was mediated via the mitochondrial pathway. These findings were further supported by cell cycle modulation and DNA/RNA synthesis studies, which indicated a significant increase in cell accumulation in the G0/G1 phase and a marked reduction in S-phase cells, alongside a substantial inhibition of DNA synthesis. The activation of caspase-3 and the cleavage of PARP, coupled with a decrease in the expression of Bcl-2 and Bcl-XL proteins, underscored the induction of apoptosis through the mitochondrial pathway. Given their high activity and pronounced effect on mitochondria function, trifluoromethyl pyrones 1f and 2f, and dihydrophthalimide 2h have been selected for further development.

Enantioselective Divergent Syntheses of Diterpenoid Pyrones.

Capitalizing a synergy between late-stage C(sp3)-H alkynylation and a series of transition metal-catalyzed alkyne functionalization reactions, we reported herein enantioselective divergent synthesis of 10 diterpenoid pyrones within 14-16 steps starting from chiral pool enoxolone, including the first enantioselective synthesis of higginsianins A, B, D, E, and metarhizin C. Our synthesis also highlights an unprecedented biomimetic oxidative rearrangement of α-pyrone into 3(2H)-furanone, as well as applications of Echavarren C(sp3)-H alkynylation reaction and Toste chiral counterion-mediated Au-catalyzed intramolecular allene hydroalkoxylation in natural product synthesis.

Development and validation of a novel risk classification tool for predicting long length of stay in NICU blood transfusion infants.

Newborns are as the primary recipients of blood transfusions. There is a possibility of an association between blood transfusion and unfavorable outcomes. Such complications not only imperil the lives of newborns but also cause long hospitalization. Our objective is to explore the predictor variables that may lead to extended hospital stays in neonatal intensive care unit (NICU) patients who have undergone blood transfusions and develop a predictive nomogram. A retrospective review of 539 neonates who underwent blood transfusion was conducted using median and interquartile ranges to describe their length of stay (LOS). Neonates with LOS above the 75th percentile (P75) were categorized as having a long LOS. The Least Absolute Shrinkage and Selection Operator (LASSO) regression method was employed to screen variables and construct a risk model for long LOS. A multiple logistic regression prediction model was then constructed using the selected variables from the LASSO regression model. The significance of the prediction model was evaluated by calculating the area under the ROC curve (AUC) and assessing the confidence interval around the AUC. The calibration curve is used to further validate the model's calibration and predictability. The model's clinical effectiveness was assessed through decision curve analysis. To evaluate the generalizability of the model, fivefold cross-validation was employed. Internal validation of the models was performed using bootstrap validation. Among the 539 infants who received blood transfusions, 398 infants (P75) had a length of stay (LOS) within the normal range of 34 days, according to the interquartile range. However, 141 infants (P75) experienced long LOS beyond the normal range. The predictive model included six variables: gestational age (GA) (< 28 weeks), birth weight (BW) (< 1000 g), type of respiratory support, umbilical venous catheter (UVC), sepsis, and resuscitation frequency. The area under the receiver operating characteristic (ROC) curve (AUC) for the training set was 0.851 (95% CI 0.805-0.891), and for the validation set, it was 0.859 (95% CI 0.789-0.920). Fivefold cross-validation indicates that the model has good generalization ability. The calibration curve demonstrated a strong correlation between the predicted risk and the observed actual risk, indicating good consistency. When the intervention threshold was set at 2%, the decision curve analysis indicated that the model had greater clinical utility. The results of our study have led to the development of a novel nomogram that can assist clinicians in predicting the probability of long hospitalization in blood transfused infants with reasonable accuracy. Our findings indicate that GA (< 28 weeks), BW(< 1000 g), type of respiratory support, UVC, sepsis, and resuscitation frequency are associated with a higher likelihood of extended hospital stays among newborns who have received blood transfusions.

A metabolomics footprinting approach using GC-MS to study inhibitory effects of the fungal metabolite diplopyrone C against nosocomial pathogen biofilms.

Seen initially as wonder drugs, the widespread and often inappropriate use of antibiotics led to the development of microbial resistances. As a result, a true emergency has arisen, and a significant need has emerged to discover and develop new safe and valuable antibiotics. The captivating chemical structure of the fungal metabolite diplopyrone C has caught our attention as an excellent candidate for a circumstantial study aimed at revealing its antimicrobial and antibiofilm activities. In this work, we describe the full analytical strategy from the isolation/identification to the evaluation of the metabolomics effect on target microorganisms of this fungal metabolite. Our results show interesting antimicrobial and antibiofilm activities of diplopyrone C against two frequently isolated nosocomial pathogens (i.e., the fungus Candida albicans and the gram-negative bacterium Klebsiella pneumoniae). Moreover, a GC-MS based metabolomics footprinting approach gave an insight into the uptake and excretion of metabolites from and into the culture medium as a response to the presence of this active substance. The workflow employed in this study is suitable to exploit natural resources for the search of lead compounds for drug development.

Kojic acid inhibits pig sperm apoptosis and improves capacitated sperm state during liquid preservation at 17°C.

The parameters of sperm apoptosis and capacitation during liquid storage at 17°C can indicate the quality of pig sperm and the potential development of early embryos. However, the effect of kojic acid (KA) on semen preservation and its mechanism has not been fully understood. In this study, we discovered that adding KA to the diluent improved the antioxidant capacity of sperm mitochondria, maintained the normal structure of sperm mitochondria, and reduced sperm apoptosis. Western blot analysis revealed that KA prevented the release of Cytochrome c from mitochondria to the cytoplasm, reduced the expression of pro-apoptosis proteins cleaved Caspase-3 and cleaved Caspase-9, and increased the expression of the antiapoptosis protein Bcl-XL. Furthermore, KA also enhanced the motility parameters, oxidative phosphorylation level, adenosine triphosphate level, and protein tyrosine phosphorylation of capacitated sperm, while preserving the acrosome integrity and plasma membrane integrity of capacitated sperm. In conclusion, this study offers new insights into the molecular mechanism of how KA inhibits porcine sperm apoptosis and improves capacitated sperm parameters. Additionally, it suggests that KA can serve as an alternative to antibiotics.

Sesquiterpenes and α-pyrones from an endophytic fungus Xylaria curta YSJ-5.

Chemical investigation of the culture extract of an endophyte Xylaria curta YSJ-5 from Alpinia zerumbet (Pers.) Burtt. et Smith resulted in the isolation of eight previously undescribed compounds including five eremophilane sesquiterpenes xylarcurenes A-E, one norsesquiterpene xylarcurene F, and two α-pyrone derivatives xylarpyrones A-B together with eight known related derivatives. Their chemical structures were extensively established based on the 1D- and 2D-NMR spectroscopic analysis, modified Mosher's method, electronic circular dichroism calculations, single-crystal X-ray diffraction experiments, and the comparison with previous literature data. All these compounds were tested for in vitro cytotoxic, anti-inflammatory, α-glucosidase inhibitory, and antibacterial activities. As a result, 6-pentyl-4-methoxy-pyran-2-one was disclosed to display significant antibacterial activity against Staphylococcus aureus and methicillin-resistant S. aureus with minimal inhibitory concentration value of 6.3 µg/mL.

Functional analysis of a putative type III polyketide synthase from deep-sea sediment metagenome.

Type III polyketide synthases (type III PKSs) are single homodimeric enzymes that produce diverse products such as phloroglucinol, pyrones, resorcinols and chalcones which are biotechnologically important molecules. In an attempt to identify new type III PKS from extreme environments, the deep-sea sediment metagenome from Bay of Bengal was screened for type III PKS genes. BLASTX analyses of Nanopore sequence derived metagenome with the in-house created PKS database revealed a full length type III PKS from a 5 kb fragment. The annotated full length type III PKS, S9PKS showed 25-30 % sequence identity towards previously characterized enzymes. To functionally characterize the gene, it was synthesized, cloned into pET28a and pColdI vectors under T7 and csp promoters, respectively, and expressed in Escherichia coli Rosetta(DE3) pLysS. The optimized PKS (OptiPKS) was expressed as inclusion bodies under both promoters. The inclusion bodies were successfully solubilised using low concentration of urea, refolded and purified using Ni-NTA Agarose resin. The purified OptiPKS was tested for functionality using fatty acyl-CoA substrates at various temperatures. High performance liquid chromatography (HPLC) analyses revealed that OptiPKS produced tri and tetraketide pyrones using C4 to C10 acyl-CoA starter substrates. Further characterization and mutation of the enzyme would reveal its functional significance. Thus, the study could be a lead for the annotation and functional characterization of putative type III PKS from environmental metagenome data.

Research on the Interaction Mechanism and Structural Changes in Human Serum Albumin with Hispidin Using Spectroscopy and Molecular Docking.

The interaction between human serum albumin (HSA) and hispidin, a polyketide abundantly present in both edible and therapeutic mushrooms, was explored through multispectral methods, hydrophobic probe assays, location competition trials, and molecular docking simulations. The results of fluorescence quenching analysis showed that hispidin quenched the fluorescence of HSA by binding to it via a static mechanism. The binding of hispidin and HSA was validated further by synchronous fluorescence, three-dimensional fluorescence, and UV/vis spectroscopy analysis. The apparent binding constant (Ka) at different temperatures, the binding site number (n), the quenching constants (Ksv), the dimolecular quenching rate constants (Kq), and the thermodynamic parameters (∆G, ∆H, and ∆S) were calculated. Among these parameters, ∆H and ∆S were determined to be 98.75 kJ/mol and 426.29 J/(mol·K), respectively, both exhibiting positive values. This observation suggested a predominant contribution of hydrophobic forces in the interaction between hispidin and HSA. By employing detergents (SDS and urea) and hydrophobic probes (ANS), it became feasible to quantify alterations in Ka and surface hydrophobicity, respectively. These measurements confirmed the pivotal role of hydrophobic forces in steering the interaction between hispidin and HSA. Site competition experiments showed that there was an interaction between hispidin and HSA molecules at site I, which situates the IIA domains of HSA, which was further confirmed by the molecular docking simulation.

[Extracellular Matrix Stiffness Induces Mitochondrial Morphological Heterogeneity via AMPK Activation]. / 细胞外基质硬度通过AMPK调控干细胞线粒体的形态异质性.

Objective: To investigate the mechanical responses of mitochondrial morphology to extracellular matrix stiffness in human mesenchymal stem cells (hMSCs) and the role of AMP-activated protein kinase (AMPK) in the regulation of mitochondrial mechanoresponses. Methods: Two polyacrylamide (PAAm) hydrogels, a soft one with a Young's modulus of 1 kPa and a stiff one of 20 kPa, were prepared by changing the monomer concentrations of acrylamide and bis-acrylamide. Then, hMSCs were cultured on the soft and stiff PAAm hydrogels and changes in mitochondrial morphology were observed using a laser confocal microscope. Western blot was performed to determine the expression and activation of AMPK, a protein associated with mitochondrial homeostasis. Furthermore, the activation of AMPK was regulated on the soft and stiff matrixes by AMPK activator A-769662 and the inhibitor Compound C, respectively, to observe the morphological changes of mitochondria. Results: The morphology of the mitochondria in hMSCs showed heterogeneity when there was a change in gel stiffness. On the 1 kPa soft matrix, 74% mitochondria exhibited a dense, elongated filamentous network structure, while on the 20 kPa stiff matrix, up to 63.3% mitochondria were fragmented or punctate and were sparsely distributed. Western blot results revealed that the phosphorylated AMPK (p-AMPK)/AMPK ratio on the stiff matrix was 1.6 times as high as that on the soft one. Immunofluorescence assay results revealed that the expression of p-AMPK was elevated on the hard matrix and showed nuclear localization, which indicated that the activation of intracellular AMPK increased continuously along with the increase in extracellular matrix stiffness. When the hMSCs on the soft matrix were treated with A-769662, an AMPK activator, the mitochondria transitioned from a filamentous network morphology to a fragmented morphology, with the ratio of filamentous network decreasing from 74% to 9.5%. Additionally, AMPK inhibition with Compound C promoted mitochondrial fusion on the stiff matrix and significantly reduced the generation of punctate mitochondria. Conclusion: Extracellular matrix stiffness regulates mitochondrial morphology in hMSCs through the activation of AMPK. Stiff matrix promotes the AMPK activation, resulting in mitochondrial fission and the subsequent fragmentation of mitochondria. The impact of matrix stiffness on mitochondrial morphology can be reversed by altering the level of AMPK phosphorylation.

Biosynthesis of Epipyrone A Reveals a Highly Specific Membrane-Bound Fungal C-Glycosyltransferase for Pyrone Galactosylation.

Epipyrone A is a unique C-galactosylated 4-hydroxy-2-pyrone derivative with an antifungal potential from the fungus Epicoccum nigrum. We elucidated its biosynthesis via heterologous expression and characterized an unprecedented membrane-bound pyrone C-glycosyltransferase biochemically. Molecular docking and mutagenesis experiments suggested a possible mechanism for the heterocyclic C-glycosylation and the importance of a transmembrane helix for its catalysis. These results expand the repertoire of C-glycosyltransferases and provide new insights into the formation of C-glycosides in fungi.

Clinically Approved Ferric Maltol: A Potent Nanozyme with Added Effect for High-Efficient Catalytic Disinfection.

Nanozyme has been proven to be an attractive and promising candidate to alleviate the current pressing medical problems. However, the unknown clinical safety and limited function beyond the catalysis of the most reported nanozymes cannot promise an ideal therapeutic outcome in further clinical application. Herein, we find that ferric maltol (FM), a clinically approved iron supplement synthesized through a facile scalable method, exhibits excellent peroxidase-like activity than natural horseradish peroxidase-like (HRP) and commonly reported Fe-based nanozymes, and also shows high antibacterial performance for methicillin-resistant Staphylococcus aureus (MRSA) elimination (100%) and wound disinfection. In addition, with added effects inherited from contained maltol, FM can accelerate skin barrier recovery. Therefore, the exploration of FM as a safe and desired nanozyme provides a timely alternative to current antibiotic therapy against drug-resistant bacteria.

Gallium maltolate, a promising low toxicity drug with curative effect on mice chronically infected with Trypanosoma evansi.

Trypanosoma evansi is a flagellate protozoan that infects a wide range of hosts, especially horses. Clinically, the infection is characterized by rapid weight loss, anemia and mobility disorders. This study evaluated the efficacy of treatment gallium maltolate (GaM) in rats infected with T. evansi in the acute and chronic phases of the disease and its influence on the enzyme and blood parameters. 48 animals (Rattus norvegicus) were divided into 8 groups (A-H) of 6 animals each, namely: A: (negative control) uninfected; B: acutely infected positive control; C: chronically infected positive control; D: acutely infected, treated with GaM for 7 days post infection (p.i.); E: acutely infected treated with GaM for 3 days before infection (b.i) and 7 days p.i.; F: chronically infected, treated with GaM for 7 days p.i.; G: chronically infected, treated with GaM for 3 days b.i. and 7 days p.i.; and H: uninfected treated with GaM for 10 days. Acute infected animals (B, D and E) had a progressive increase in parasitemia and were died or euthanized before completing treatment days (5th days p.i.) as they had high parasitemia (over 100 field trypanosomes in the blood smear). Thus, it can be concluded that GaM was not effective against an acute infection. In untreated chronically infected animals (C) the parasitemia also increased progressively and they were euthanized on the 7th day p.i.. The chronically infected and treated animals (F and G) showed low parasitemia and after treatment became negative, showing no trypanosomes in the bloodstream until the 50th day of the experiment. Thus, we conclude that GaM was effective against chronic infections. In uninfected and treated animals (H) hematological, biochemical and enzymatic parameters had no significant changes when compared to the negative control group (A) demonstrating the low toxicity of GaM.

Hyperhenrones: Prenylated α-pyrones with anti-inflammatory activity from Hypericum henryi.

Fourteen previously undescribed α-pyrone derivatives (1-14) together with four known analogs (15-18) were isolated from a traditional Chinese medicinal plant Hypericum henryi. Compounds (+)/(-)-1, 2, and 3 share a rare 6/6/4/6/6 polycyclic skeleton. Compound 14 was the first example of a 7,7-dimethyl-pyran-4-one moiety. Their structures were elucidated using comprehensive spectroscopic analyses and electronic circular dichroism calculations. The anti-inflammatory activities of 1-18 were screened in lipopolysaccharide-induced RAW264.7 cells. Among them, compounds 14, (+)-18, and (-)-18 exhibited inhibitory effects against nitric oxide production in LPS-induced RAW264.7 cells. Additionally, compound 14 suppressed the expression of cyclooxygenase-2 and inducible nitric oxide synthase in LPS-induced RAW264.7 cells. Furthermore, preliminary mechanism studies indicated that compound 14 suppressed the phosphorylation and degradation of the inhibitor of NF-κB, and this led to the inhibition of NF-κB activation.

Undescribed α-pyrone-containing mycotoxins and an eremophilane-type sesquiterpenoid isolated from Aspergillus aureoterreus and their cytotoxicity.

Four previously undescribed and highly oxygenated α-pyrone-containing mycotoxins designated citreoviridins (E‒H), and an unreported eremophilane-type sesquiterpenoid namely aureoterrolide N, were isolated from the culture broth of Aspergillus aureoterreus. Those isolates were inferred from extensive spectroscopic methods and theoretical computation, where their absolute configurations were unambiguously determined by coupling constants following an empirical rule for the acyclic vicinal diol, theoretical ECD calculation, and NMR computation using the GIAO method and DP4+ analysis. Among them, citreoviridins E‒H are four stereoisomers of a citreoviridin derivative, featuring a methylated α-pyrone, an oxidized polyene linker, and a tetrahydrofuran ring. Cytotoxicity assay of all isolates demonstrated that aureoterrolide N exhibited weak inhibitory effect against human cancer cell line HL-60 with an inhibition rate of 55.2% at 40.0 µM.

Antibacterial p-terphenyl and α­pyrone derivates isolated from the marine-derived actinomycete Nocardiopsis sp. HDN154086.

Assisted by OSMAC strategy, one new p-terphenyl and two new α­pyrone derivates, namely nocarterphenyl I (1) and nocardiopyrone D-E (2-3), were obtained and characterized from the marine sediment-derived actinomycete Nocardiopsis sp. HDN154086. The structures of these compounds were determined on the basis of MS, NMR spectroscopic data and single-crystal X-ray diffraction. Compound 1 with a rare 2,2'-bithiazole structure among natural products showed promising activity against five bacteria with MIC values ranging from 0.8 to 1.6 µM and 3 exhibited notable antibacterial activity against MRSA compared the positive control ciprofloxacin.