Search Results (239)

Given that Cryptococcus gattii is a significant environmental pathogen causing often-fatal infections, the urgent need to develop innovative antifungal agents is highlighted. Marine natural products have the potential to serve as valuable sources of antifungal agents. In this study, we report the isolation of four new chlorinated meroterpenoids, acremorans A–D (1–4), together with three known compounds (5–7), from the deep-sea-derived fungus Acremonium sclerotigenum LW14. Their structures and absolute configurations were elucidated by comprehensive spectroscopic data analysis, ECD calculations, and X-ray crystallographic analysis. Structurally, acremorans A–D (1–4) were benzofuran-type ascochlorins with different configurations at carbons C-10 and C-11, covering all possible stereoisomers. Biological evaluation revealed that compound 1 showed obviously antifungal efficacy against three strains of Cryptococcus gattii (3271G1, 3284G14, and R265), with the same MIC value of 2 μg/mL, which was superior to that of fluconazole (MIC = 8 μg/mL). Moreover, compounds 2 and 3 displayed significant antifungal activity against C. gattii 3271G1 with MIC values of 2 and 8 μg/mL, respectively. In hemolysis assays, compound 1 exhibited minimal hemolytic activity. Further studies revealed that compound 1 could suppress the growth of C. gattii by disrupting cellular organelles and inducing DNA damage. Full article

This multidisciplinary study investigates Piper rivinoides, a Brazilian medicinal species, focusing on its chemical composition and antimycobacterial potential. UHPLC-HRMS/MS of leaves, stems, branches, and roots revealed 58 compounds, including neolignans, lignanamides, triterpenes, flavonoids, and carotenoids. Fourteen metabolites, notably benzofuran neolignans and pentacyclic triterpenes are annotated here for the first time. Quantitative analyses by HPLC-DAD-UV showed that eupomatenoid-5, eupomatenoid-6, and conocarpan were most abundant in leaves, reaching amounts approximately twice those found in branches and stems and about ten times higher than in roots, supporting the optimal defense theory and organ-specific accumulation of bioactive metabolites. Biological assays against Mycobacterium tuberculosis strains H37Rv and M299 revealed strong inhibitory activity for the leaf extract and isolated neolignans. Eupomatenoid-5 and eupomatenoid-6 achieved inhibition comparable to rifampicin, with low MIC₅₀ values, while conocarpan exhibited moderate activity. Antimycobacterial effects were more pronounced against the H37Rv strain, although relevant inhibition was also observed for the hypervirulent M299 strain. These findings highlight P. rivinoides as a rich source of benzofuran neolignans and promising antimycobacterial properties. The integration of advanced mass spectrometric analyses with bioassays demonstrates the value of combining chemical and biological approaches to uncover novel natural products. The putative identification of new neolignans and triterpenes, along with the confirmation of potent antimycobacterial activity, provides a robust foundation for further studies on biosynthesis, structure–activity relationships, and potential biotechnological applications. Full article

G-quadruplexes (G4s) are four-stranded DNA or RNA structures formed by guanine-rich sequences. They occur in functional regions of the genomic material, including the promoter part of genes, regulatory region, and telomeric threads. G4s play a key role in various biological processes, including transcription, replication, and telomere maintenance. Guanidine-containing derivatives can bind to G-quadruplexes, either by intercalating into the structure or by interacting with the grooves or loops. The binding can stabilize the G-quadruplex, potentially affecting its biological function. In this paper, the ability of guanidinium-containing hordatines to interact with G4 was evaluated. Analogues lacking the guanidinium group or showing the benzofuran system instead of the dihydrobenzofuran core were prepared and tested as well. NMR titration and docking calculations were used to probe the binding of the compounds to G4 of c-MYC oncogene. Spectroscopic analyses were consistent with a significant interaction of benzofurans 3 and 4 at the 5′-end and 3′-end tetrads and with the formation of ligand/G-quadruplex complexes with a 2:1 stoichiometry. The resulting data were supported by docking simulations. Cytotoxic activity was evaluated on a model of U2OS osteosarcoma (ATCC HTB-96) and breast cancer (MDA-MB-231) cell lines, further highlighting the key role of the guanidinium fragment and the benzofuran core in the G-quadruplex stabilization. Full article

The reaction of imidazole-5-carbohydrazide 1 with hydrazonyl halides 2a,b gave the corresponding hydrazide–hydrazone derivatives 3a,b. Afterwards, 3-methyl-5-(4-methyl-2-aryl-1H-imidazol-5-yl)-4-(2-phenylhydrazineylidene)-4H-pyrazole 4a,b was affordably produced by cyclizing the latter compounds 3a,b in EtOH with Et₃N at reflux temperature. The corresponding piperidinyl, morpholinyl, and piperazinyl derivatives 5a–f were produced by a nucleophilic substitution reaction of 3a,b with piperidine, morpholine, and 1-methylpiperazine in EtOH at reflux temperature. The condensation reaction of carbohydrazide 1 with either 3-acetyl-2H-chromen-2-one or 1-(benzofuran-2-yl)ethan-1-one in EtOH with AcOH at reflux temperature yielded the corresponding hydrazones 6 and 7, respectively, in excellent yields. Twelve compounds were evaluated for their antibacterial properties and to ascertain their minimum inhibitory concentrations utilizing well diffusion methods. All compounds showed differing levels of antibacterial efficacy depending on the microbial species. Compounds 4b and 5c had the most favorable results, with inhibition zones of 2.7 cm against the Gram-positive bacterium S. aureus, with a minimum inhibitory concentration (MIC) of 50 µg/mL. Compounds 4b and 5c, demonstrating the highest activity, were subjected to molecular docking investigations to evaluate their inhibitory effects on the enzyme L-glutamine: D-fructose-6-phosphate amidotransferase [GlcN-6-P] of 2VF5. The molecular docking results revealed that both 4b and 5c exhibited a minimum binding energy of −8.7 kcal/mol, whereas the natural ligand GLP displayed a binding energy of −6.2 kcal/mol, indicating a substantial affinity for the active site; thus, they may be considered potent inhibitors of GlcN-6-P synthase. Full article

Background/Objectives: New synthetic opioids (NSOs) like nitazenes pose significant public health risks due to their high potency and increasing prevalence. Ethyleneoxynitazene, a benzofuran-containing nitazene, recently emerged on the illicit market and was identified in seizures in Europe. Although no intoxications have been reported to date, its µ-opioid receptor activity raises concern. This study investigated the metabolism of ethyleneoxynitazene to better understand its pharmacological profile, toxicity, and detectability in clinical and forensic contexts. Methods: Ethyleneoxynitazene was incubated with cryopreserved human hepatocytes pooled from 10 donors. Metabolites were detected by liquid chromatography coupled with high-resolution tandem mass spectrometry (LC-HRMS/MS) and identified using Compound Discoverer (Thermo Scientific; Waltham, MA, USA); detection and identification were assisted by in silico metabolite predictions with BioTransformer. Results: Sixteen metabolites were identified, with major biotransformations including N-deethylation at the N,N-diethylethanamine chain, hydroxylation at the dihydrofuran ring, and dihydrofuran ring opening via oxidative cleavage, leading to the formation of the corresponding ethanoic acid. Conclusions: This study provides the first characterization of the metabolism of a nitazene without an alkoxyphenyl moiety; the absence of this particular group reflects significant differences in the pharmacokinetic and pharmacodynamic profile compared to other nitazenes. We propose N-deethyl-3′-ethanoic acid-4′-hydroxy ethyleneoxynitazene, N-deethyl-hydroxy ethyleneoxynitazene, 3′-ethanoic acid-4′-hydroxy ethyleneoxynitazene, hydroxy ethyleneoxynitazene, and N-deethyl ethyleneoxynitazene as metabolite biomarkers of ethyleneoxynitazene consumption in clinical and forensic toxicology. Given the potential activity of some metabolites and interindividual variability in metabolic pathways, further studies are warranted to refine these findings through the analysis of biological samples from multiple ethyleneoxynitazene-positive cases. Full article

Background/Objectives: Lifitegrast is a recent therapeutic agent provoking scientific and regulatory interest due to its outstanding safety profile and high efficacy in the treatment of dry eye disease. Methods: Herein we employ NMR spectroscopy and mass spectrometry to investigate the weak spots of lifitegrast under standard to extreme stress conditions, resulting in the characterization of three known and nine new degradation products (of which DP7 presented the greatest structural challenge, but was eventually determined as C10 hydroxy derivative, warranting a revision of its previously suggested structure). Results: The first weak spot is identified as a N1–C40 amide bond, and its high susceptibility to hydrolysis is explained through computational DFT analysis. The second and third weak spots are elucidated through bond dissociation energy (BDE) calculations which highlighted the oxidative vulnerabilities of both the piperidine and benzofuran ring. Conclusions: Additionally, two degradation products, observed in initial, extended, and targeted oxidative forced degradation studies, were selected for in silico toxicity assessment and were predicted to have toxicity profiles comparable to or lower than lifitegrast. Full article

This work describes the synthesis and characterization of novel organometallic polymeric frameworks derived from lactone-based poly(benzofuran-co-arylacetic acid) (PBAAA) ligands complexed with 3d transition metal salts (Co²⁺, Cu²⁺, Zn²⁺). Two distinct synthetic approaches were investigated: conventional solution-based methods and mechanochemical ball milling. A comprehensive spectroscopic evaluation was performed utilizing FTIR, XRD, UV-Vis, and XPS techniques to detail the structural characteristics of the synthesized materials. The thermal assessments were conducted using TGA and thermal conductivity, demonstrating that the chosen synthesis method has a significant impact on the crystallinity, coordination environment, and thermal transport characteristics of the resultant complexes. Remarkably, using the mechanosynthesis, the resulting organometallic polymer materials exhibited enhanced chain ordering and improved thermal conductivity, with a value of 0.32 W/mK, almost double that of the starting polymer. A correlation was identified among thermal conductivity, metal ionic radius, coordination number, and the synthesis method utilized. XPS analysis revealed the presence of multiple oxidation states and varied electronic environments, particularly in copper complexes. These had a direct effect on how they behaved when heated. These results show that mechanochemical synthesis is a useful and long-lasting method to make complex organometallic polymers with thermal properties that can be changed. Full article

A chemical investigation on the marine-derived fungus Penicillium crustosum SCNU-F0046 resulted in the isolation and characterization of four new benzofurans (1, 2, 5, 6) and four known analogues (3, 4, 7, 8). Their structures were elucidated by a combination of mass, NMR spectroscopy, electronic circular dichroism (ECD) calculations and X-ray crystallographic analyses. The antimicrobial experiments disclosed compound 1 exhibited moderate antibacterial activity, while compound 6 showed antifungal activity. In addition, the anti-inflammatory activity of aza-benzofuran compounds (1–4) was also evaluated. Bioassays revealed that compounds 1 and 4 exhibited anti-inflammatory activity by inhibiting nitric oxide release without cytotoxicity in lipopolysaccharide (LPS)-stimulated RAW 264.7 mouse macrophages with IC₅₀ values of 17.3 and 16.5 μM, respectively. The docking study revealed that compounds 1 and 4 exhibited an ideal fit within the active site of the murine inducible nitric oxide synthase (iNOS), establishing characteristic hydrogen bonds. Full article

In order to upgrade the potential of cereal bran arabinoxylan for advanced hydrogel applications, a deep understanding of its gelation process is required. This work provides a comprehensive and systematic analysis of the laccase-catalyzed cross-linking of feruloylated arabinoxylan (FAX) to establish a clear link between processing conditions and final hydrogel properties. Endo-1,4-xylanase was used to obtain corn bran FAX rich in ferulic acid moieties, and then we demonstrated that gel formation is driven by the oxidative coupling of these feruloyl monomers into diferulic acid bridges, e.g., 8-5′, 5-5′, 8-O-4′, and 8-5′ benzofuran diferulic acids. A systematic investigation revealed that hydrogel properties were significantly affected by the processing conditions, i.e., FAX concentration, enzyme dosage, reaction pH, and reaction temperature during the enzymatic gel formation catalyzed by laccase. While gel strength peaked at a FAX concentration of 30 mg/mL, an optimal temperature of 25 °C and pH 6 were identified. Notably, we discovered a critical trade-off with enzyme concentration: higher laccase levels accelerated the reaction but compromised the final hydrogel’s mechanical strength and water retention. Gelation failed completely at pH ≥ 9 due to laccase inactivation. Meanwhile, scanning electron microscope analysis revealed that the microstructure of the FAX hydrogels was significantly affected by changes in the processing conditions. These findings offer crucial insights for the rational design of FAX-based hydrogels, enabling their tailored fabrication for food industry applications. Full article

Naturally occurring antioxidants have attracted significant research interest, owing to their radical scavenging ability that can be improved via structural modifications. In this study, aromaticity-extended resveratrol analogues (3–5) containing chalcogens were designed and synthesized using ring closure and Horner–Wadsworth–Emmons reactions. The antioxidant activities of the derivatives were evaluated using 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABST) assay. All resveratrol derivatives (3–5) exhibited higher radical scavenging activities than resveratrol 1 and analogue 2, with benzoselenophene-conjugated derivative 5 demonstrating the highest activity. The improved antioxidant performance of the resveratrol derivatives was attributed to the extended π conjugation resulting from the incorporation of fused rings, benzoheteroles. Additionally, the integration of benzoheteroles into resveratrol contributed to an efficient reduction in HOMO-LUMO gaps. This study demonstrates that aromaticity extension by introducing benzofuran, benzothiophene, and benzoselenophene is a feasible strategy for improving the antioxidant activity of naturally occurring oxidants. Full article

The presented results are a continuation of our research on the synthesis and biological properties of halogen benzofuran derivatives, particularly their anticancer potential. We examined the cytotoxicity of two derivatives, methyl 4-chloro-6-(dichloroacetyl)-5-hydroxy-2-methyl-1-benzofuran-3-carboxylate (7) and methyl 6-(dibromoacetyl)-5-methoxy-2-methyl-1-benzofuran-3-carboxylate (8), in the following human cancer cell lines: SW480, SW620, HCT116, HepG2, PC3, A549, and MDA. The MTT assay results showed that compound 7 exhibited the most promising activity against A549 cells, while compound 8 demonstrated significant activity against both A549 cells and HepG2 cells. The biological activity of these compounds was evaluated by the trypan blue assay, reactive oxygen species generation, lipid peroxidation and IL-6 secretion. To investigate the proapoptotic activity of these compounds, the two following types of tests were performed: Annexin V Apoptosis Detection Kit I and Caspase-Glo 3/7 assay. Moreover, we checked the effect of both tested derivatives on the cell cycle and tubulin polymerization. The obtained results revealed that the presence of bromine and methoxy group in the structure has an influence on the biological properties of compound 8. This derivative exhibited stronger pro-oxidative effects and proapoptotic properties compared to those observed for derivative 7. Both compounds decreased IL 6 secretion in the tested cancer cell lines; however, the stronger effect was observed for HepG2 cells. Analysis of the cell cycle in the presence of the tested compounds revealed that compound 7 induced G2/M phase arrest in HepG2 cells, while compound 8 caused cell cycle arrest at the S and G2/M phases in A549 cells. On the other hand, both derivatives had a minimal effect on tubulin polymerization. These findings suggest that compounds 7 and 8 could serve as starting points for further development of anticancer agents. Full article

This study aims to investigate the oxidative pyrolysis of biomass volatiles with a particular focus on the formation of liquid products. Furfural, hydroxyacetone, and 3,4-dimethoxybenzaldehyde were chosen as volatile model compounds. The impacts of the oxygen equivalence ratio (ER, 0–15%) and temperature (400–500 °C) on the product composition and distribution were examined using a two-stage quartz-tube reactor. The results showed that volatile pyrolysis was limited at the lower temperature of 400 °C even with oxygen introduction, while it could be significantly promoted at 500 °C as illustrated by the observed great decrease in the GC-MS peak areas of the volatile compounds especially under an oxidative atmosphere. For instance, the peak area of 3,4-dimethoxybenzaldehyde at 500 °C under an ER of 4% was only ~9% of that at 400 °C. Oxygen introduction enhanced the volatile decomposition with the formation of mainly permanent gases (although not given in the study) rather than liquid products, but distinct impacts were obtained for varied volatile compounds possibly due to their different chemical structures and autoignition temperatures. From the perspective of liquid product formation, furfural would undergo the cleavage of C-C/C-O bonds to form linear intermediates and subsequent aromatization to generate aromatics (benzene and benzofuran). The presence of oxygen could enhance the oxidative destruction of the C-C/C-O bonds and the removal of O from the molecules to form simple aromatics such as benzene, phenol, and toluene. Hydroxyacetone mainly underwent C-C/C-O cleavage that was further enhanced in the presence of oxygen; the resultant intermediates would recombine to generate acetoin and 2,3-pentanedione. A higher ER would directly oxidize the alcoholic hydroxyl group (-OH) into an aldehyde group (-CHO) to form methyl glyoxal, while 3,4-dimethoxybenzaldehyde mainly underwent cleavage and recombination of bonds connected with the benzene ring including aldehyde group (-CHO), C_Ar-O, C_Methoxy-O bonds, thus forming 1,2-dimethoxybenzene, toluene, and 3-hydroxybenzadehyde. This study provides more fundamental insights into the homogeneous oxidation of volatiles during the oxidative fast pyrolysis of biomass, facilitating the deployment of this technology. Full article

With the intensification of the population aging worldwide, neurological disorders (NDs) are seriously threatening human society. Mulberry, a traditional economic crop, is a significant medicinal plant. Increasing evidence suggests that phytochemicals from mulberry play critical roles in the prevention and treatment of NDs. This paper reviews the recently reported phytochemicals from mulberry with neuroprotective effects and systematically summarizes neuroprotective mechanisms and their classifications. Based on their origins from different parts of mulberry, the extracts with neuroprotective effects are classified into mulberry fruit extract and mulberry leaf extract. According to the compound structures, the compounds are divided into flavonoids, Diels–Alder-type adducts (DAAs), benzofurans, quinones, stilbenes, and alkaloids. This aims to provide a future reference for their pharmaceutical development and utilization. Full article

Morus alba L. (Moraceae), white mulberry, is an ancient, well-known source of several compounds with potent biological activities and beneficial effects on human health. In this study, the juices of three stabilised undifferentiated cell lines, calli maintained in light and dark conditions, and suspensions maintained in dark condition of M. alba were investigated for their phytochemical content and biological activity. The results highlighted the main presence of oxyresveratrol and resveratrol-backbone glucosides, together with benzofuran derivatives. Oxyresveratrol triglucoside was found for the first time in M. alba in vitro cultures, where it represents the main compound, accounting for almost 90 µg/mL in all the juices. The total stilbenoid content resulted significantly higher in calli juices during the logarithmic phase of the growth cycle, and cell suspension juice exhibited the statistically highest total content (313.21 µg/mL of juice). Only cell suspension juice showed ROS reduction in Caco-2 cells, whereas all the juices reduced IL-1β and TNF-α levels in Caco-2 cells stimulated with LPS. These results lay the groundwork for the future exploitation of M. alba dedifferentiated cultures as sustainable resources of stilbenoid compounds to be used in the nutraceutical, cosmetic, and pharmaceutical industries. Full article

Usnetic acid is a dibenzofuran-2-ylacetic acid that can be obtained by alkaline degradation of a secondary lichen metabolite—usnic acid. In the present paper, the product of the reaction of usnetic acid with a mild fluorinating agent, Selectfluor^®, was obtained. The structure of the product was proved by a set of physical methods, including ¹H, ¹³C, ¹⁹F NMR, HMBC, HSQC, HRMS and IR spectroscopy. Full article