Search Results (225)

Pancreatic cancer cells exhibit a remarkable ability to tolerate nutrient deprivation, a phenomenon termed “austerity,” which enables their survival within the hypovascular tumor microenvironment. Conventional anticancer therapies frequently fail to effectively target these resilient neoplastic cells, posing a significant challenge to the therapeutic management of pancreatic cancer. Consequently, targeting austerity, the ability of cancer cells to tolerate nutrient starvation, represents a promising anti-austerity strategy for developing novel pancreatic cancer therapeutics. In this study, we investigated calliviminone A (CVM-A), a phloroglucinol–meroterpenoid isolated from Callistemon citrinus leaves, for its anti-austerity activity against PANC-1 human pancreatic cancer cells. Calliviminone A exhibited potent preferential cytotoxicity in nutrient-deprived medium (NDM) with a PC₅₀ of 0.57 µM, while showing minimal toxicity in nutrient-rich Dulbecco’s Modified Eagle’s medium (IC₅₀ = 45.2 µM), indicating a favorable therapeutic index. Real-time live-cell imaging revealed that CVM-A induced significant morphological changes, including cell shrinkage and membrane blebbing, leading to cell death within 24 h of NDM. Furthermore, under normal nutrient conditions in Dulbecco’s Modified Eagle’s Medium (DMEM), CVM-A significantly inhibited PANC-1 cell migration (up to 47% reduction at 20 µM) and colony formation (over 80% suppression at 25 µM), suggesting its antimetastatic potential. Western blot studies demonstrated that CVM-A downregulated key survival components of the PI3K/Akt/mTOR signaling pathway, completely inhibiting Akt and p-Akt at 2.5 µM in NDM, and suppressing insulin-induced Akt activation. These findings highlight CVM-A as a promising lead compound for developing novel anticancer therapies that target the adaptive survival mechanisms and metastatic potential of pancreatic cancer in nutrient-deprived microenvironments. Full article

Chiral covalent organic frameworks (COFs) hold great promise in heterogeneous asymmetric catalysis due to their designable structures and well-defined chiral microenvironments. However, precise control over the pore size of chiral COFs to optimize asymmetric catalytic performance remains challenging. Herein, we designed a proline-derived dihydrazide chiral monomer (L-DBP-Boc), which was subjected to Schiff-base reactions with two aromatic aldehydes of different lengths, 1,3,5-triformyl phloroglucinol (BTA) and 4,4′,4″-(1,3,5-triazine-2,4,6-triyl)tribenzaldehyde (TZ), to construct two hydrazone-linked chiral COFs with distinct pore sizes (L-DBP-BTA COF and L-DBP-TZ COF). Interestingly, the Boc protecting groups were removed in situ during COF synthesis. We systematically investigated the catalytic performance of these two chiral COFs in asymmetric aldol reactions and found that their pore sizes significantly influenced both catalytic activity and enantioselectivity. The large-pore L-DBP-TZ COF (pore size: 3.5 nm) exhibited superior catalytic performance under aqueous conditions at room temperature, achieving a yield of 98% and an enantiomeric excess (ee) value of 78%. In contrast, the small-pore L-DBP-BTA COF (pore size: 2.0 nm) showed poor catalytic performance. Compared to L-DBP-BTA COF, L-DBP-TZ COF demonstrated a 1.69-fold increase in yield and a 1.56-fold enhancement in enantioselectivity, possibly attributed to the facilitated diffusion and transport of substrates and products within the larger pore, thus improving the accessibility of active sites. This study presents a facile synthesis of pyrrolidine-functionalized chiral COFs and establishes the possible structure–activity relationship in their asymmetric catalysis, offering new insights for the design of efficient chiral COF catalysts. Full article

Zoonotic viral diseases have continued to threaten global public health in recent decades, with rodent-borne viruses being significant contributors. Infection by rodent-carried hantaviruses (HV) can result in hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS) in humans, with varying degrees of morbidity and mortality. However, no Food and Drug Administration (FDA) vaccines or therapeutics have been approved for the treatment of these diseases. In an effort to identify antiviral bioactive molecules, we isolated four oligomeric phloroglucinols from Callistemon rigidus leaves, including two new phloroglucinol trimers, callistemontrimer A and B, along with two previously characterized phloroglucinol dimers, rhodomyrtosone B and rhodomyrtone. We evaluated the anti-Hantaan virus (HTNV) activity of these compounds. Notably, callistemontrimer A demonstrated higher anti-HTNV activity compared to ribavirin. Mechanistic studies revealed that callistemontrimer A exerted its antiviral effects by inhibiting viral replication, likely through interaction with RNA-dependent RNA polymerase (RdRp) of HTNV, as supported by molecular docking analysis. These results highlight oligomeric phloroglucinols as promising lead candidates for the development of anti-HV therapeutics. Full article

The endemic Patagonian conifer, Austrocedrus chilensis, is threatened by the pathogen Phytophthora austrocedri. This study presents the first histological and histochemical analysis of A. chilensis affected by this pathogen. We examined the stem tissues of naturally infected adult trees (over 30 years old) and artificially inoculated saplings (8–12 years old) to identify the pathogen’s colonization strategies and the tree’s histological responses. Using light and scanning electronic microscopy along with several histochemical techniques (Lugol, toluidine blue, vanillin-HCl, Phloroglucinol, Calcofluor white, and aniline blue), we found that P. austrocedri can grow in all active tissues, leading to cambium and parenchyma necrosis. The pathogen spreads through sieve cells and tracheids, moving to the adjacent cells via sieve plates and bordered pits and colonizing nearby parenchyma cells. We observed loss of starch in necrotic tissues. In contrast, starch accumulation and an increase in the number of polyphenolic cells occur in the healthy areas adjacent to the margins of the lesion, indicating a tree’s induced defense mechanisms. The tree’s responses include cambium reprogramming, which leads to the formation of traumatic resin ducts, alterations in cell shape and size, and the deposition of phenolic compounds. We analyze the tree responses and discuss their potential relationship with a methyl jasmonate-induced defense and a hypersensitive-like response. Full article

Background/Objectives: Lactic acid bacteria produce biofilms in meat products that contribute to the products’ deterioration, reduction in quality, and shortened shelf life. Although LAB are generally considered benign, certain strains create slime and cause significant drops in pH. The study’s goal was to identify and characterize LAB strains from sausage products that are capable of biofilm formation, and to evaluate the inhibitory effects of E. bicyclis methanol extract, its ethyl acetate fraction, and phloroglucinol, as well as to synthesize AuNPs, and assess their efficacy in controlling biofilm formation. Methods: Slime or biofilm-producing LAB bacteria were isolated from commercial sausages and identified using 16S rRNA gene sequencing. Lactobacillus sakei S10, which can tolerate high salt concentrations and cold temperatures, was chosen as a representative strain. The isolates were subsequently tested for hemolytic activity, salt and temperature tolerance, and carbohydrate consumption patterns. To evaluate antibiofilm potential, marine-derived compounds from Eisenia bicyclis, such as phloroglucinol (PG), crude methanolic extracts, ethyl acetate fractions, and gold nanoparticle (AuNP) formulations, were tested in situ on sausage surfaces against L. sakei S10 and common pathogens (Pseudomonas aeruginosa and Staphylococcus aureus). The biofilm-inhibitory effects of the extracts, PG, and PG-AuNPs were estimated using the colony-counting method. Results: The PG-AuNPs had an average particle size of 98.74 nm and a zeta potential of −29.82 mV, indicating nanoscale dimensions and considerable colloidal stability. Structural analysis confirmed their spherical form and crystalline structure, as well as the presence of phenolic groups in both reduction and stabilization processes. Among the studied treatments, the PG and PG-AuNPs had the strongest antibiofilm activities, dramatically lowering biofilm biomass, particularly for P. aeruginosa and L. sakei S10. However, the inhibitory effects were less prominent in in situ conditions than in in vitro testing, highlighting the complexity of real food matrices. Conclusions: The results of this study indicate that polyphenolic compounds obtained from marine sources, particularly in nano-formulated forms, have a great deal of potential as natural antibiofilm products. Enhancing the microbiological safety of processed meat products and extending their shelf life could be accomplished through the application of these polyphenolic compounds in food packaging or surface treatments. Full article

In this study, we combined automated annotation tools with targeted dereplication based on MS/MS fragmentation pathway studies to identify polycyclic polyprenylated acylphloroglucinols (PPAPs) in Hypericum species, using H. patulum and H. hookeranium as a case study. These species, extensively used in traditional medicine, exhibit morphological similarities that often result in misidentification. Following UHPLC-HRMS/MS analysis of plant extracts, a molecular network approach facilitated a comprehensive comparison of their chemical composition, assigning specific clusters to O-glycosylated flavonoids and PPAPs. Eight peaks, including quercitrin, isoquercitrin, procyanidins, chlorogenic acid, quercetin, and glycosylated derivatives, were annotated from the GNPS database. For PPAPs, despite the structural complexity posing challenges for automated annotation using public databases, our targeted-dereplication strategy, relying on in-house spectral data, led to the putative identification of 22 peaks for H. patulum and H. hookeranium. Key compounds such as hyperforin, hyperscabrone K, and garcinialliptone M were detected in both species, underscoring their chemical similarity. MS/MS fragmentation pathways, particularly the successive losses of isobutene and isoprenyl units, emerged as a consistent signature for PPAP detection and may be useful for selecting PPAP-enriched extracts or fractions for further phytochemical investigations. Full article

Biomaterials play a crucial role in the long-term success of bone implant treatment. The accumulation of bacterial biofilm on the implants induces inflammation, leading to implant failure. Modification of the implant surface with bioactive molecules is one of the strategies to improve biomaterial compatibility and limit inflammation. In this study, whey protein isolate (WPI) fibrillar coatings were used as a matrix to incorporate biologically active phenolic compound phloroglucinol (PG) at different concentrations (0.1% and 0.5%) on titanium alloy (Ti6Al4V) scaffolds. Successful Ti6Al4V coatings were validated by X-ray photoelectron spectroscopy (XPS), showing a decrease in %Ti and increases in %C, %N, and %O, which demonstrate the presence of the protein layer. The biological activity of PG-enriched WPI (WPI/PG) coatings was assessed using bone-forming cells, human bone marrow-derived mesenchymal stem cells (BM-MSCs). WPI/PG coatings modulated the behavior of BM-MSCs but did not have a negative impact on cell viability. A WPI with higher concentrations of PG increased gene expression relative to osteogenesis and reduced the pro-inflammatory response of BM-MSCs after biofilm stimulation. Autoclaving reduced WPI/PG bioactivity compared to filtration. By using WPI/PG coatings, this study addresses the challenge of improving osteogenic potential while limiting biofilm-induced inflammation at the Ti6Al4V surface. These coatings represent a promising strategy to enhance implant bioactivity. Full article

Hypericum hircinum L., commonly known as goat St. John’s wort or stinking tutsan, is a medicinal plant native to the Mediterranean basin and widespread across Europe and parts of the Middle East. It has a long history of traditional uses in folk medicine to treat respiratory diseases, wounds, and burns and to relieve migraine, rheumatism, and muscular pains. Despite numerous scientific studies shading light on the phytochemical profile and on the beneficial properties of the plant extracts, a comprehensive overview of the current knowledge is missing. In this paper, we summarized the available information on botany, traditional uses, phytochemistry, and pharmacological properties of Hypericum hircinum from peer-reviewed articles published till March 2025 in PubMed, ScienceDirect, Wiley, Springer, ACS, Scielo, and Web of Science databases. The presence of numerous valuable compounds, including terpenes, phenolic acids, flavonoids, and phloroglucinols, is reported as well as the wide range of pharmacological properties, such as antimicrobial, antifungal, antiviral, antidepressant, anti-collagenase, anti-α-glucosidase, and antioxidant activities, together with non-pharmacological properties. The data reported in this review contribute to a deeper understanding of the biological properties of the species and pave the way for further investigation of its potential applications. Full article

Background: Fungal infections pose an increasingly predominant threat to human and animal health. Modified compounds derived from chemo-diverse natural products offer enhanced therapeutic efficacies and promising approaches to combat life-threatening fungal pathogens. Methods: We performed biosynthetic gene clusters analysis of 2,4-diacetylchloroglucoside (DAPG) in 4292 shotgun metagenomes samples from the healthy and diseased skin. Then, we assessed the antifungal activity of DAPG and the derivative 2,4-diproylphloroglucinol (DPPG) against pathogenic fungi by minimum inhibitory concentrations. The inhibitory effects of DPPG were measured using hyphal growth assay and spore germination assay. Concurrently, the mechanism of DPPG on Aspergillus fumigatus was investigated in membrane permeability and fluidity. The therapeutic efficacy was evaluated in a Galleria mellonella infection model. Results: We observed a significantly higher abundance of bacteria harboring DAPG biosynthetic clusters on healthy skin compared to diseased skin. Further, we designed and synthesized a series of phloroglucinol derivatives based on DAPG and obtained an antifungal candidate DPPG. DPPG not only exhibited robust antifungal activity against Aspergillus spp. and Candida spp. but also impaired hyphal growth and spore germination of A. fumigatus in vitro. A mechanism study showed that DPPG reduced membrane fluidity and increased the leakage of cellular contents, resulting in membrane perturbation and fungal death. Lastly, the therapeutic efficacy of DPPG was confirmed in a G. mellonella infection model. Conclusions: Our study demonstrates that DPPG is a potent scaffold to combat invasive fungal infections. Full article

Nitrophenols are persistent organic pollutants that pose serious environmental and health risks due to their toxic and lipophilic nature. Their persistence arises from strong aromatic stability and resistance to biodegradation, while their lipophilicity facilitates bioaccumulation, exacerbating ecological and human health concerns. To address this challenge, this study focuses on the synthesis and characterization of two different types of hybrid multi-core magnetic catalysts: (i) cobalt ferrite (Co-Fe₂O₄), which exhibits ferrimagnetic properties, and (ii) magnetite (Fe₃O₄), which demonstrates close superparamagnetic behavior and is coated with a novel and less hazardous phloroglucinol–glyoxal-derived resin. This approach aims to enhance catalytic efficiency while reducing the environmental impact, offering a sustainable solution for the degradation of nitrophenols in aqueous matrices. Transmission electron microscopy (TEM) images revealed the formation of a multi-core shell structure, with carbon layer sizes of 6.6 ± 0.7 nm for cobalt ferrite and 4.2 ± 0.2 nm for magnetite. The catalysts were designed to enhance the stability and performance in catalytic wet peroxide oxidation (CWPO) processes using sol–gel and solution combustion synthesis methods, respectively. In experiments of single-component degradation, the carbon-coated cobalt ferrite (CoFe@C) catalyst achieved 90% removal of 2-nitrophenol (2-NP) and 96% of 4-nitrophenol (4-NP), while carbon-coated magnetite (Fe₃O₄@C) demonstrated similar efficiency, with 86% removal of 2-NP and 94% of 4-NP. In the multi-component system, CoFe@C exhibited the highest catalytic activity, reaching 96% removal of 2-NP, 99% of 4-NP, and 91% decomposition of H₂O₂. No leaching of iron was detected in the coated catalysts, whereas the uncoated materials exhibited similar and significant leaching (CoFe: 5.66 mg/L, Fe₃O₄: 12 mg/L) in the single- and multi-component system. This study underscores the potential of hybrid magnetic catalysts for sustainable environmental remediation, demonstrating a dual-function mechanism that enhances catalytic activity and structural stability. Full article

During the conventional biomass fractionation, the degradation and dissolution of lignin and hemicellulose result in a complex extract which remains very challenging for the thorough separation and purification of a wide variety of fractionated products, limiting their further utilization. Herein, we proposed a facile and efficient strategy for fractionating biomass and simultaneously in situ converting of both lignin and hemicellulose into single products using a formic acid–phloroglucinol system. The introduced phloroglucinol could react with lignin fragments and hemicellulose-derived products, and the generated intermediate product from hemicellulose can be further condensed with lignin fragments, finally forming single lignin-based functional biopolymers containing heterocyclic structures. Only small amounts of hemicellulosic derivatives, such as oligosaccharides, monosaccharides, furfural, and 5-HMF, were detected in the extracted solution, indicating a highly directional and effective in situ conversion process of hemicellulose. The constructed specific structures on fabric surfaces by using the chelation between lignin-based functional biopolymers and metal ions achieved the preparation of functional fabrics with stable hydrophobicity. The dynamic contact angle of water droplets on the surface of prepared fabric only decreased from 122° to 116.8° over 30 min. This work strategy provides an ideal route to maximize the utilization of both lignin and hemicellulose without involving complex separation and purification procedures. This strategy is the first demonstration of using the targeted fractionation system to achieve the simultaneous conversion of hemicellulose and lignin into single functional biopolymers directly from lignocellulosic biomass. Full article

Caffeine is a nitrogenous base that naturally occurs in coffee (Cafea arabica), tea (Thea sinensis), and cocoa (Theobroma cacao). Chemically, caffeine is 1,3,5-trimethylxanthine, a purine analogue. Due to significant human consumption, caffeine effects have been widely studied. Being a natural xanthine derivative, the key degradative enzyme is xanthine oxidase, converting caffeine into 1-methyluric acid. Ecologically, caffeine is believed to act as a repellent molecule against insect feeding behavior. Caffeine’s chemical similarity to purines and plant hormones motivated this study, establishing the potential for cellular de-differentiation and re-differentiation. For this, a highly hormone-responsive plant species, Ornithogalum dubium, was used. As caffeine has been shown to induce endoreplication, the potential for new germlines in O. dubium is attractive. Using tissue culture, a range of caffeine concentrations were used (0.0125 mg/L to 2.0 mg/L) without additional hormones. A significant difference (p > 0.05) was observed for intermediate concentrations of 0.0125, 0.025, and 0.05 mg/L when compared to the control (no hormones). The highest rates of callus induction were obtained at a concentration of 0.025 mg/mL. Higher concentrations were phytotoxic (1.0 mg/L or greater). To conclude, caffeine-regenerated plants were not dissimilar to those obtained from canonical hormones. Full article

Background/Objectives: This study aims to gain insights into the antimicrobial and antiherpetic activity of hyperforin-rich Hypericum perforatum L. (HP) extract using nanostructured lipid carriers (NLCs) as delivery platforms. Methods: Two established NLC specimens, comprising glyceryl behenate and almond oil or borage oil, and their extract-loaded counterparts (HP-NLCs) were utilized. Their minimal bactericidal/fungicidal concentrations (MBC; MFC) were investigated against Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 10145, Klebsiella pneumoniae ATCC 10031, and Candida albicans ATCC 10231. The anti-herpesvirus (HSV-1) potential was evaluated concerning antiviral and virucidal activity and impact on viral adsorption. Results: The borage oil-based extract-loaded nanodispersion (HP-NLC2) exhibited pronounced microbicidal activity against S. aureus (MBC 6.3 mg/mL), K. pneumoniae (MBC 97.7 µg/mL), and C. albicans (MFC < 48.8 µg/mL), unlike the almond oil-containing sample (HP-NLC1), which showed only weak inhibition of the fungal growth. HP-NLC2 was found to be less cytotoxic and to suppress HSV-1 replication slightly more than HP-NLC1, but generally, the effects were weak. Neither the empty lipid nanoparticles nor the HP extract-loaded carriers expressed activity against E. coli, P. aeruginosa, the HSV-1 extracellular virions, or viral adhesion. Conclusions: It could be concluded that both HP-NLC samples revealed only minor antiherpetic potential of the hyperforin-rich extract, but HP-NLC2 demonstrated significant antibacterial and antimycotic activity. Therefore, the latter was featured as a more convenient HP-carrier system for nano-designed dermal pharmaceutical formulations. Such a thorough investigation of hyperforin-determined anti-HSV-1 effects and antibacterial and antimycotic properties, being the first of its kind, contributes to the fundamental knowledge of HP and reveals new perspectives for the utilization, limitations, and therapeutic designation of its non-polar components. Full article

The rising demand for bioactive compounds from marine resources highlights the need for sustainable separation technologies. This study introduces an integrated process combining ultrasound-assisted extraction (USAE) and resin purification (RP) to isolate phlorotannins from Durvillaea incurvata, a brown seaweed with significant biomedical potential. Using a 32.5% ethanol–water solvent system for USAE followed by RP on Diaion HP-20 resin, phlorotannins were enriched 2.4-fold, with simultaneous removal of interfering compounds such as mannitol (~100%), which was demonstrated by FTIR and HPLC-IR analysis. Advanced characterization using UHPLC-QToF-MS/MS identified five novel phlorotannins with polymerization degrees of 3 to 8 phloroglucinol units in both USAE extracts and post-RP. Mass balance based on spectrophotometric measurements indicated a purification factor of ~2, confirming process effectiveness. RP streams showed distinct phlorotannin profiles, with one phlorotannin exceeding 70% relative abundance. However, MS/MS results showed significantly lower recoveries than spectrophotometric data, revealing a novel insight into RP purification. These findings highlight the critical role of comprehensive chemical characterization in optimizing sustainable phlorotannin extraction from seaweed. They propose a framework for scalable, eco-efficient technologies for achieving high-purity phlorotannin recovery. This approach facilitates the development of phlorotannin-based applications in the nutraceutical and pharmaceutical industries. Full article

Humulones are a family of homolog natural products obtained from the strobiles of humulus lupulus, or hops plants. Structurally, they consist of substituted phloroglucinols with two isoprenyl side chains, a carbonyl group and a quaternary ring carbon substituted with a hydroxyl group. The three most prominent homologs are n-, co- and ad-humulone, containing isobutyl, isopropyl and secbutyl ketone groups, respectively. When solutions of humulones are exposed to UV light, they undergo stereoselective isomerization to the five-membered ring trans-isohumulones. A photoreactor was assembled from strip LEDs in close contact with UV-transparent tubing. This reactor allowed continuous-flow chemical synthesis of the isohumulones. The yield, conversion and product throughput are compared for the humulones, using LEDs emitting white, blue and ultraviolet light (visible, 400 nm, and 365 nm, respectively). Using an optimized continuous-flow reactor, a throughput of 0.43 g/h was obtained for trans-n-isohumulone. Full article