The role of ClO- in the physiological functioning of organisms is significant. In this paper, the four fluorescent probes HONx (HON1, HON2, HON3 and HON4) were prepared based on oxyanthracene through the introduction of different substituents, and their photophysical properties were investigated, among which the AIE effect of HON1 was the most significant, and therefore the fluorescent \"turn-off\" ClO- probe HON1-CN was chosen to be prepared by constructing the ClO- recognition site hydrazone bond at HON1. The ClO- recognises the hydrazone group in the probe HON1-CN, and when the hydrazone bond is broken, the aldehyde group is released, generating HON1 with yellow fluorescence. The probe HON1-CN is highly selective and stable for the detection of ClO- with a detection limit of 0.48 μM and a more than 10-fold increase in fluorescence intensity when the fluorescence is \'switched on\', and to a lesser extent, the probe is also very good for the detection of hypochlorite ClO- in the pericarp. Finally, HON1-CN has also been used to detect the presence of ClO- in HeLa cells and zebrafish.

Glioma, a common and highly malignant central nervous system tumor, markedly influences patient prognosis via interactions with glioma-associated macrophages. Previous research has revealed the anticancer potential of β-mangostin, a xanthone derivative obtained from the mangosteen fruit. This research investigated the role of β-mangostin on microglia in the glioma microenvironment and evaluated the efficacy of β-mangostin combined with anti-PD-1 antibody (αPD-1) in glioma-bearing mice. The results showed that, β-mangostin attenuated M2 polarization in BV2 cells and promoted M1-related interleukin (IL)-1β and IL-6 secretion, thereby inhibiting glioma invasion. In addition, β-mangostin improved the anti-glioma effects of αPD-1 and increased CD8+T cell and M1-type microglia infiltration. Mechanistically, β-mangostin bound to the stimulator of interferon genes (STING) protein, which is crucial for the anti-tumor innate immune response, and promoted STING phosphorylation in microglia, both in vivo and in vitro. These results provide insights into its mode of action and supporting further investigation into β-mangostin as a therapeutic agent.

Introduction: There is a growing interest in studying natural products for the identification of novel lead compounds for drug development for treating inflammatory diseases. Although some studies have focused anti-inflammatory activity of benzophenones and xanthones, exploring additional targets such as enzymes and cytokines, involved in their inflammatory response could provide more comprehensive understanding of the compounds\' anti-inflammatory effects. In this study, four xanthones ananixanthone (1), smeathxanthone A (2), smeathxanthone B (3), and 1,3,5,8-tetrahydroxy-2-(3-methybut-2-enyl)-4-(3,7-dimethyloct-2,6-dienyl) xanthone (4); and three benzophenones guttiferone O (5), guttiferone M (6), and aristophenone A (7) from Garcinia smeathmannii (Planch. & Triana) Oliv. were investigated for their effect on nitric oxide production, cyclooxygenase, lipoxygenase inhibition, and Th1/Th2 cytokines production in activated RAW 264.7 macrophages. Methods: The Griess reagent method and the ferrous oxidation-xylenol orange assay were used to evaluate the inhibition of NO production and the 15-lipoxygenase activity respectively. Cyclooxygenase activity was assessed using the fluorometric COX activity assay kit and measurement of Th1/Th2 cytokines was performed using a flow cytometer. Results: All the tested compounds exhibited a dose-dependent inhibition of NO production with varying degrees of inhibitory effects on 15-LOX activity. Compound (6), displays the best inhibitory effect on COX-1/COX-2 activity. A general trend of the tested compounds on cytokines profiles revealed that compound (5) showed a pronounced enhancement of anti-inflammatory cytokines (IL-4 and IL-10). Conclusion: This observation supports future exploration of ananixanthone (1), guttiferone O (5), and guttiferone (6) as potential candidates for the development of anti-inflammatory drugs.

A recently synthesized aminated 3,4-dioxygenated xanthone (Xantifoul2) was found to have promising antifouling (AF) effects against the settlement of the macrofouler Mytilus galloprovincialis larvae. Preliminary assessment indicated that Xantifoul2 has reduced ecotoxicological impacts: e.g., being non-toxic to the marine crustacea Artemia salina (<10 % mortality at 50 μM) and showing low bioconcentration factor in marine organisms. In order to meet the EU Biocidal Product Regulation, a preliminary hazard assessment of this new nature-inspired antifouling (NIAF) agent was conducted in this work. Xantifoul2 did not affect the swimming ability of the planktonic crustacean Daphnia magna, the growth of the diatom Phaeodactylum tricornutum, and the cellular respiration of luminescent Gram-negative bacteria Vibrio fischeri, supporting the low toxicity towards several non-target marine species. Regarding human cytotoxicity, Xantifoul2 did not affect the cell viability of retinal human cells (hTERT-RPE-1) and lipidomic studies revealed depletion of lipids involved in cell death, membrane modeling, lipid storage, and oxidative stress only at a high concentration (10 μM). Accelerated degradation studies in water were conducted under simulated sunlight to allow the understanding of putative transformation products (TPs) that could be generated in the aquatic ecosystems. Both Xantifoul2 and photolytic-treated Xantifoul2 in the aqueous matrix were therefore evaluated on several nuclear receptors (NRs). The results of this preliminary hazard assessment of Xantifoul2, combined with the high degradation rates in water, provide strong evidence of the safety of this AF agent under the evaluated conditions, and provide the support for future validation studies before this compound can be introduced in the market.

In search for new metabolites from the stem bark of Calophyllum soulattri and Calophyllum gracilentum, led to the isolation of a new xanthone, soulaxanthone (1), along with four other known metabolites, euxanthone (2), calopolyanolide E (3), calanolide E (4) and friedelin (5). The structures of these compounds were identified and elucidated using spectroscopic techniques such as 1H NMR,13C NMR, COSY, DEPT, HSQC, HMBC, MS and FTIR. The antibacterial activities of compounds 1-5, as well as the extracts, were tested against five bacterial strains. Soulaxanthone (1) exhibited moderate activity against Pseudomonas aeruginosa with an MIC value of 25 µg/mL. Hexane (non-polar) extract from both plants exhibited moderate activity against Enterobacter cloacae (MIC = 250 µg/mL). Calopolyanolide E (3) and friedelin (5) showed bactericidal activity against Enterobacter cloacae (MBC = 50 µg/mL), thus the compounds have the potential to serve as a new lead for developing effective antibacterial medication.

Three new xanthone derivatives irpexols A-C (1-3) and five known xanthones including three dimeric ones were successfully isolated from Irpex laceratus A878, an endophytic fungus of the family Irpicaceae from the medicinal plant Pogostemon cablin (Blanco) Bentham (Lamiaceae). The structures of these compounds were elucidated by extensive spectroscopic analyses including ultraviolet-visible spectroscopy (UV), infrared spectroscopy (IR), mass spectrometry (MS), and nuclear magnetic resonance (NMR). All of the three new compounds (1-3) share a de-aromatic and highly‑oxygenated xanthone skeleton. In addition, the cytotoxic activity of compounds 1-8 were evaluated against SF-268, MCF-7, HepG2, and A549 tumor cell lines. The results revealed that compound 6 showed moderate cytotoxic activity with the IC50 values ranging from 24.83 to 45.46 μM, while the IC50 values of the positive control adriamycin was ranging from 1.11 to 1.44 μM.

OBJECTIVE: This study aimed to discover novel antifungals targeting Candida albicans glyceraldehyde-3-phosphate dehydrogenase (CaGAPDH), have an insight into inhibitory mode, and provide evidence supporting CaGAPDH as a target for new antifungals.
METHODS: Virtual screening was utilized to discover inhibitors of CaGAPDH. The inhibitory effect on cellular GAPDH was evaluated by determining the levels of ATP, NAD, NADH, etc., as well as examining GAPDH mRNA and protein expression. The role of GAPDH inhibition in C. albicans was supported by drug affinity responsive target stability and overexpression experiments. The mechanism of CaGAPDH inhibition was elucidated by Michaelis-Menten enzyme kinetics and site-specific mutagenesis based on docking. Chemical synthesis was used to produce an improved candidate. Different sources of GAPDH were used to evaluate inhibitory selectivity across species. In vitro and in vivo antifungal tests, along with anti-biofilm activity, were carried out to evaluate antifungal potential of GAPDH inhibitors.
RESULTS: A natural xanthone was identified as the first competitive inhibitor of CaGAPDH. It demonstrated in vitro anti-C. albicans potential but also caused hemolysis. XP-W, a synthetic side-chain-optimized xanthone, demonstrated a better safety profile, exhibiting a 50-fold selectivity for CaGAPDH over human GAPDH. XP-W also exhibited potent anti-biofilm activity and displayed broad-spectrum anti-Candida activities in vitro and in vivo, including multi-azole-resistant C. albicans.
CONCLUSIONS: These results demonstrate for the first time that CaGAPDH is a valuable target for antifungal drug discovery, and XP-W provides a promising lead.

Alzheimer\'s disease (AD) is a progressive neurodegenerative disorder characterized by the accumulation of amyloid-β (Aβ) protein aggregates, leading to synaptic dysfunction and neuronal cell death. In this study, we used a comprehensive approach encompassing in vitro assays, computational analyses, and an in vivo Caenorhabditis elegans model to evaluate the inhibitory effects of various xanthones, focusing on Garcinone D (GD), on Aβ42 oligomer formation. Dot blot analysis revealed concentration-dependent responses among xanthones, with GD consistently inhibiting Aβ42 oligomer formation at low concentrations (0.1 and 0.5 μM, inhibitions of 84.66 ± 2.25% and 85.06 ± 6.57%, respectively). Molecular docking and dynamics simulations provided insights into the molecular interactions between xanthones and Aβ42, highlighting the disruption of key residues involved in Aβ42 aggregation. The neuroprotective potential of GD was established using transgenic C. elegans GMC101, with substantial delays in paralysis reported at higher concentrations. Our findings show that GD is a potent suppressor of Aβ42 oligomer formation, suggesting its potential as a therapeutic candidate for AD. The concentration-dependent effects observed in both in vitro and in vivo models underscore the need for nuanced dose-response assessments. These findings contribute novel insights into the therapeutic landscape of xanthones against AD, emphasizing the multifaceted potential of GD for further translational endeavors in neurodegenerative disorder research.

Xanthones comprise a large family of heterocycles displaying fascinating biological properties. Many synthetic protocols have been developed for the preparation of natural and nonnatural xanthone derivatives. Among them, condensation reactions between salicylic acid derivatives and phenol partners are highly desirable. Those reactions can be satisfactorily performed using Eaton\'s reagent (P2O5 in CH3SO3H). Despite being highly effective with a variety of substrates, this approach presents limitations that depend on the electronic nature of the reaction precursors. The scope and limitations of the Eaton\'s reagent-mediated preparation of xanthones are herein presented and discussed. In short, this approach is limited to the utilization of very electron-rich phenol substrates (like phloroglucinol compounds), or to electron-rich phenol precursors (like resorcinol derivatives) via the isolation of benzophenone intermediates in this latter case. Electron-poor phenols are not amenable to this transformation with Eaton\'s reagent.

In order to cure a range of ailments, scientists have investigated a number of bioactive antioxidant compounds produced from natural sources. Mangiferin, a C-glycosyl xanthone-structured yellow polyphenol, is abundant in mangoes and other dietary sources. In-depth examinations found that it is effective in the treatment of a variety of disorders due to its antiviral, anti-inflammatory, antiproliferative, antigenotoxic, antiatherogenic, radioprotective, nephroprotective, antihyperlipidemic, and antidiabetic properties. However, it is recognised that mangiferin\'s poor bioavailability, volatility, and limited solubility restrict its therapeutic usefulness. Over time, effective solutions to these problems have arisen in the shape of effective delivery methods. The current articles present a summary of the several researches that have updated Mangiferin\'s biopharmaceutical characteristics. Additionally, strategies for enhancing the bioavailability, stability, and solubility of this phytodrug have been discussed. This review provides detailed information on the development of innovative Mangiferin delivery methods such as nanoparticles, liposomes, micelles, niosomes, microspheres, metal nanoparticles, and complexation, as well as its therapeutic applications in a variety of sectors. This article provides effective guidance for researchers who desire to work on the formulation and development of an effective delivery method for improved magniferin therapeutic effectiveness.