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Calophyllum species are well known due to their abundance of potentially beneficial phytochemicals, such as xanthones, coumarins, and others. However, Calophyllum gracilentum is an understudied specie with very limited information. Medicinal plants have been proven to have therapeutic potential in managing neurological disorders associated with acetylcholinesterase (AChE) dysregulation. Still, there has been little investigation on Calophyllum plants for this purpose. Herein, we report on the isolation of a new oxygenated xanthone 5,10-dihydroxy-9-methoxy-2,2-dimethyl-12-(3-methylbut-2-enyl) pyrano[3,2- b ] xanthen-6(2 H)-one (1) and eleven known xanthones (2–12), three chromanone acids (13–15), and phytosterols (16–18), respectively from the stem bark of the Calophyllum gracilentum. The evaluation of AChE inhibitory activity showed that all the extracts and xanthones (2 , 5 , 6 , 8 , 9 , 12) tested have potential AChE inhibitory activity. Compounds (5) and (12) are prospective AChE inhibitors with IC 50 values of 1.8 ± 0.0001 and 4.0 ± 0.0002 µmol/L. The molecular docking analysis demonstrated compound (5) and compound (12) bind well to the active site which is the anionic site containing Trp 84 and Asp 72 in the of Torpedo californica acetylcholinesterase (TcAChE) through π-π stacking, hydrogen bonding, and π-donor hydrogen bond from the xanthone ring, besides π-alkyl and π-σ interactions from the substituent group with the binding energy of −11.1 kcal/mol for compound (5) and binding energy of −10.4 kcal/mol for compound (12). [Display omitted] • A new xanthone, 12 known xanthones, chromanone acids and phytosterols were isolated. • 5 and 12 showed strong inhibition of AChE activity. • 5 and 12 bound to the AChE active site by π-π stacking. [ABSTRACT FROM AUTHOR]

Xanthones, a class of polyketide derivatives characterized by a dibenzo‐γ‐pyrone core structure, are aromatic oxygenated cyclic compounds extensively found in nature. They are known for their diverse biological activities, including anti‐Alzheimer, antitumor, and antidiabetic properties, which have spurred extensive research into their therapeutic potential. One of the most significant challenges facing mankind currently is the development of antibiotic resistance in pathogenic microbes making microbial infections increasingly difficult to treat. The formation of biofilms enhances bacterial resistance to antibiotics, immune defenses, and environmental stresses. In this review, we have categorized xanthones, both of biological origin and synthesized, based on their structure and summarized the recent studies on their ability to inhibit Gram‐positive and ‐negative bacteria as well as the various underlying mechanisms that contribute to their microbicidal activity. These mechanisms include inhibition of virulence factors and biofilm formation, interaction with cell membranes, and interference with cell wall synthesis and DNA replication. In addition, we have listed the various methods involved in biofilm inhibition and the structure‐activity relationship of various xanthone molecules, highlighting how xanthone derivatives exhibit increased antibacterial activity. With the growing concern of antibiotic resistance, exploring natural compounds like xanthones to study their interaction with bacterial cells is crucial for identifying new treatment options. [ABSTRACT FROM AUTHOR]

Polygalae Radix is a commonly used traditional Chinese medicine with multiple pharmacological activities. Modern research have revealed that saponins, xanthones, and oligosaccharide esters are its effective component groups. However, up to date the chemical substances in these effective component groups are still unclear, which has become a fundamental scientific issue needing to be addressed. In our study, an analysis strategy based on targeted tandem mass spectrometry (MS/MS) analysis was proposed to comprehensively identify the chemical substances in effective component groups. First, the extract of the Polygalae Radix was detected by ultra‐performance liquid chromatography coupled with electrospray ionization–orbitrap mass spectrometry in a full MS scan mode to minimize the losses of signals; second, the precursor ions of all compounds were extracted from the obtained full MS scan data using Compound Discoverer software; third, the interested precursor ions were locked based on their molecular features and constructed in a precursor ion list; finally, each precursor ion in the list was subjected to targeted MS/MS analysis for structure characterization. Using our analysis strategy, a total of 565 components were successfully identified. [ABSTRACT FROM AUTHOR]

Xanthones are chemical substances in higher plants, marine organisms, and lower microorganisms. The most prevalent naturally occurring sources of xanthones are those belonging to the families Caryophyllaceae, Guttiferae, and Gentianaceae. Structurally, xanthones (9H xanthan-9-one) are heterocyclic compounds with oxygen and a γ-pyrone component. They are densely packed with a two-benzene ring structure. The carbons in xanthones are numbered from their nucleus and biosynthetic construct. They have mixed shikimate-acetate (higher plants) and acetate-malonate (lower organisms) biosynthetic origins, which influence their classification. Based on the level of oxidation of the C-ring, they are classified into monomers, dimers, and heterodimers. While based on the level of oxygenation or the type of ring residue, they can be categorized into mono-, di-, tri-, tetra-, penta- and hexa-oxygenated xanthones, bis-xanthones, prenylated and related xanthones, xanthonolignoids, and other miscellaneous xanthones. This structural diversity has made xanthones exhibit considerable biological properties as promising antioxidant, antifungal, antimicrobial, and anticancer agents. Structure-activity relationship studies suggest C-1, C-3, C-6, and C-8 as the key positions that influence the biological activity of xanthones. Furthermore, the presence of functional groups, such as prenyl, hydroxyl, glycosyl, furan, and pyran, at the key positions of xanthones, may contribute to their spectrum of biological activity. The unique chemical scaffolds of xanthones, their notable biological activities, and the structure–activity relationships of some lead molecules were discussed to identify lead molecules as possible drug candidates. [ABSTRACT FROM AUTHOR]

Objective: α-Mangostin (1), a xanthone predominantly abundant in Garcinia mangostana, exhibits diverse pharmacological activities. As reported in our previous study, it also shows inhibitory activities against neuraminidase of the influenza virus. In the present study, we investigated α-mangostin derivatives produced by γ-irradiation to identify more effective neuraminidase inhibitors. Methods: α-Mangostin (1) in methanol (2.439 mM) was treated with 200 Gy of gamma (60Co) irradiation (10 kGy/h). Five radiolysis products were isolated using combined chromatographic techniques, and their structures were identified using one- and two-dimensional nuclear magnetic resonance and high-resolution electrospray ionization mass spectroscopy. The neuraminidase inhibitory activities of all compounds were evaluated and compared. Results: Five derivatives (2 − 6) including two new compounds, 13,6-trihydroxy-2-(2-hydroxyethyl)-7-methoxy-8-(3-methylbut-2-enyl)-9 H -xanthen-9-one (5) and 13,6-trihydroxy-2-(4-hydroxy-2-methoxy-3,3-dimethylbutyl)-7-methoxy-8-(3-methylbut-2-enyl)-9 H -xanthen-9-one (6), were obtained by γ-irradiating α-mangostin dissolved in methanol. All derivatives exhibited IC50 values of 7.84–44.66 μM against neuraminidase. Mangostanin (4) exhibited an IC50 of 7.84 μM, which is 1.6- and 1.8-fold more potent than that of 1 and quercetin (positive control), respectively. In addition, all compounds exhibited competitive inhibition. Conclusion: Our results suggest that γ-irradiation is an effective method for structural modification of α-mangostin and it derivative, mangostanin is potential neuraminidase inhibitor. [ABSTRACT FROM AUTHOR]

Abstract Background Malaria is a major global health concern, particularly in tropical and subtropical countries. With growing resistance to first-line treatment with artemisinin, there is an urgent need to discover novel antimalarial drugs. Mesua ferrea Linn., a plant used in traditional medicine for various purposes, has previously been investigated by our research group for its cytotoxic properties. The objective of this study was to explore the compounds isolated from M. ferrea with regards to their potential antiplasmodial activity, their interaction with Plasmodium falciparum lactate dehydrogenase (PfLDH), a crucial enzyme for parasite survival, and their pharmacokinetic and toxicity profiles. Methods The isolated compounds were assessed for in vitro antiplasmodial activity against a multidrug-resistant strain of P. falciparum K1 using a parasite lactate dehydrogenase (pLDH) assay. In vitro cytotoxicity against Vero cells was determined using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The interactions between the isolated compounds and the target enzyme PfLDH were investigated using molecular docking. Additionally, pharmacokinetic and toxicity properties were estimated using online web tools SwissADME and ProTox-II, respectively. Results Among the seven compounds isolated from M. ferrea roots, rheediachromenoxanthone (5), which belongs to the pyranoxanthone class, demonstrated good in vitro antiplasmodial activity, with the IC50 being 19.93 µM. Additionally, there was no toxicity towards Vero cells (CC50 = 112.34 µM) and a selectivity index (SI) of 5.64. Molecular docking analysis revealed that compound (5) exhibited a strong binding affinity of − 8.6 kcal/mol towards PfLDH and was stabilized by forming hydrogen bonds with key amino acid residues, including ASP53, TYR85, and GLU122. Pharmacokinetic predictions indicated that compound (5) possessed favorable drug-like properties and desired pharmacokinetic characteristics. These include high absorption in the gastrointestinal tract, classification as a non-substrate of permeability glycoprotein (P-gp), non-inhibition of CYP2C19, ease of synthesis, a high predicted LD50 value of 4,000 mg/kg, and importantly, non-hepatotoxic, non-carcinogenic, and non-cytotoxic effects. Conclusions This study demonstrated that compounds isolated from M. ferrea exhibit activity against P. falciparum. Rheediachromenoxanthone has significant potential as a scaffold for the development of potent antimalarial drugs.

Background. Salicylic acid is an important phytohormone in plants, influencing various functions such as senescence, respiration, and stress resistance. Despite extensive studies the role of salicylic acid in stress, its effects under normal conditions are less understood. This study explores the influence of salicylic acid on the biosynthesis of important biochemical compounds such as ascorbic acid, rutin, and other phenolic compounds in wheat (Triticum aestivum L.), aiming to elucidate potential applications in agriculture. Materials and Methods. Wheat variety 'Podolyanka' was treated with 0.05 mM salicylic acid and grown under controlled conditions. Biochemical analyses were studied on 7, 10 and 20 days of growth to using the spectrophotometric method for the determination of ascorbic acid, rutin, total phenolic compounds, anthocyanins, flavonoids, and xanthones. Methods included chromatography on the plate with silicagel for rutin. Results and Discussion. Salicylic acid treatment significantly increased the ascorbic acid content in wheat shoots at all studied stages. There was also a notable increase in rutin content in the early growth phase. However, the content of other phenolic compounds, such as xanthones, generally decreased under salicylic acid treatment. Intriguingly, anthocyanin content was increased, suggesting a complex interaction within the biosynthetic pathways influenced by salicylic acid. The study also revealed correlations among different phenolic compounds, indicating intertwined metabolic pathways. Conclusion. Salicylic acid enhances the biosynthesis of specific phenolic compounds like ascorbic acid and rutin in wheat, which can have implications for agricultural practices aiming at improving plant resilience and nutritional quality. The differential impact of SA on various phenolic compounds underscores the complexity of plant biochemical pathways and highlights the need for further research to fully understand these interactions and their practical applications.

Despite the existence of various therapeutic approaches, diabetes mellitus and its complications have been an increasing burden of mortality and disability globally. Hence, it is necessary to evaluate the efficacy and safety of medicinal plants to support existing drugs in treating diabetes. Xanthones, the main secondary metabolites found in Gentiana dinarica and Gentiana utriculosa, display various biological activities. In in vitro cultured and particularly in genetically transformed G. dinarica and G. utriculosa roots, there is a higher content of xanthones. The aim of this study was to investigate and compare antidiabetic properties of secondary metabolites (extracts) prepared from these two Gentiana species, cultured in vitro and genetically transformed with those collected from nature. We compare HPLC secondary metabolite profiles and the content of the main extract compounds of G. dinarica and G. utriculosa methanol extracts with their ability to scavenge DPPH free radicals and inhibit intestinal α-glucosidase in vitro. Anti-hyperglycemic activity of selected extracts was tested further in vivo on glucose-loaded Wistar rats. Our findings reveal that the most prominent radical scavenging potential and potential to control the rise in glucose level, detected in xanthone-rich extracts, were in direct correlation with an accumulation of xanthones norswertianin and norswertianin-1-O-primeveroside in G. dinarica and decussatin and decussatin-1-O-primeveroside in G. utriculosa. [ABSTRACT FROM AUTHOR]

In order to improve naturally occurring xanthones' anticancer properties, chemical synthesis is proposed. In this study, from eight novel xanthone derivatives coupled to morpholine or aminoalkyl morpholine, only the two most active ones were chosen. For additional enhancement of the anticancer activity of our tested compounds, we combined chemotherapy with hyperthermia in the range of 39–41 °C, from which the mild conditions of 39 °C were the most influencing. This approach had a profound impact on the anticancer properties of the tested compounds. TOV-21G and SC-OV-3 ovarian cell line motility and metastasis behavior were tested in native and hyperthermia conditions, indicating decreased wound healing properties and clonogenic activity. Similarly, the expression of genes involved in metastasis was hampered. The expression of heat shock proteins involved in cancer progression (Hsc70, HSP90A, and HSP90B) was significantly influenced by xanthone derivatives. Chemotherapy in mild hyperthermia conditions had also an impact on decreasing mitochondria potential, visualized with JC-1. Synthetic xanthone ring modifications may increase the anticancer activity of the obtained substances. Additional improvement of their activity can be achieved by applying mild hyperthermia conditions. Further development of a combined anticancer therapy approach may result in increasing currently known chemotherapeutics, resulting in a greater recovery rate and diminishment of the cytotoxicity of drugs. [ABSTRACT FROM AUTHOR]

Comparative study of phenolic compound composition was performed by HPLC-UV and HPLC-MS techniques using raw materials of Hedysarum alpinum L. plants introduced into the dendrological ecosystem of the Siberian Botanical Garden of Tomsk State University as well as the callus culture of the same species. The callus culture of Hedysarum alpinum was obtained on Murashige and Skoog nutrient medium with the addition of 1.0 mg/L 2,4-D and 0.1 mg/L 6-benzylaminopurine (6-BAP) and was subsequently cultivated on the medium containing α-NAA (2.0 mg/L) and 6-BAP (0.5 mg/L). The culture was characterized by activated phenylpropanoid pathway, which gave rise to the formation of flavonoids, isoflavones, xanthones, and other substances. The total content of flavonoids (calculated on a per quercetin basis) and formononetin in the extracts of callus culture was lower than in the extracts from introduced plants by 35 and 11%, respectively, whereas the content of mangiferin in callus extracts was more than 50% higher than in the extracts of aerial plant parts. [ABSTRACT FROM AUTHOR]

Hypericum beanii N. Robson, a perennial upright herb, predominantly inhabits temperate regions. This species has been utilized for the treatment of various inflammation-related diseases. One new xanthone 3,7-dihydroxy-1,6-dimethoxyxanthone (1) and twenty-three known xanthones (2–24) were isolated from the aerial parts of H. beanii. The structure of the new compound was determined based on high-resolution electrospray ionization mass spectroscopy (HR-ESIMS), nuclear magnetic resonance (NMR), Infrared Spectroscopy (IR), ultraviolet spectrophotometry (UV) spectroscopic data. The anti-inflammatory effects of all the isolates were assessed by measuring the inhibitory effect on nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages. Compounds 3,4-dihydroxy-2-methoxyxanthone (15), 1,3,5,6-tetrahydroxyxanthone (19), and 1,3,6,7-tetrahydroxyxanthone (22) exhibited significant anti-inflammatory effects at a concentration of 10 μM with higher potency compared to the positive control quercetin. Furthermore, compounds 15, 19, and 22 reduced inducible NO synthase (iNOS), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-6, and cyclooxygenase 2 (COX-2) mRNA expression in the LPS-stimulated RAW 264.7 macrophages, suggesting that these compounds may mitigate the synthesis of the aforementioned molecules at the transcriptional level, provisionally confirming their anti-inflammatory efficacy. [ABSTRACT FROM AUTHOR]

Background: Malaria is a major global health concern, particularly in tropical and subtropical countries. With growing resistance to first-line treatment with artemisinin, there is an urgent need to discover novel antimalarial drugs. Mesua ferrea Linn., a plant used in traditional medicine for various purposes, has previously been investigated by our research group for its cytotoxic properties. The objective of this study was to explore the compounds isolated from M. ferrea with regards to their potential antiplasmodial activity, their interaction with Plasmodium falciparum lactate dehydrogenase (PfLDH), a crucial enzyme for parasite survival, and their pharmacokinetic and toxicity profiles. Methods: The isolated compounds were assessed for in vitro antiplasmodial activity against a multidrug-resistant strain of P. falciparum K1 using a parasite lactate dehydrogenase (pLDH) assay. In vitro cytotoxicity against Vero cells was determined using the MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay. The interactions between the isolated compounds and the target enzyme PfLDH were investigated using molecular docking. Additionally, pharmacokinetic and toxicity properties were estimated using online web tools SwissADME and ProTox-II, respectively. Results: Among the seven compounds isolated from M. ferrea roots, rheediachromenoxanthone (5), which belongs to the pyranoxanthone class, demonstrated good in vitro antiplasmodial activity, with the IC50 being 19.93 µM. Additionally, there was no toxicity towards Vero cells (CC50 = 112.34 µM) and a selectivity index (SI) of 5.64. Molecular docking analysis revealed that compound (5) exhibited a strong binding affinity of − 8.6 kcal/mol towards PfLDH and was stabilized by forming hydrogen bonds with key amino acid residues, including ASP53, TYR85, and GLU122. Pharmacokinetic predictions indicated that compound (5) possessed favorable drug-like properties and desired pharmacokinetic characteristics. These include high absorption in the gastrointestinal tract, classification as a non-substrate of permeability glycoprotein (P-gp), non-inhibition of CYP2C19, ease of synthesis, a high predicted LD50 value of 4,000 mg/kg, and importantly, non-hepatotoxic, non-carcinogenic, and non-cytotoxic effects. Conclusions: This study demonstrated that compounds isolated from M. ferrea exhibit activity against P. falciparum. Rheediachromenoxanthone has significant potential as a scaffold for the development of potent antimalarial drugs. [ABSTRACT FROM AUTHOR]

As part of a long-term campaign to document, study, and conserve the Heroes tapestries from The Cloisters collection at The Metropolitan Museum of Art, organic colorant analysis of Julius Caesar (accession number 47.101.3) was performed. Analysis with liquid chromatography–quadrupole time-of-flight mass spectrometry (LC-qToF-MS) revealed the presence of several multiply chlorinated xanthones produced only by certain species of lichen. Various lichen dye sources have been documented in the literature for centuries and are classified as either ammonia fermentation method (AFM) or boiling water method (BWM) dyes based on their method of production. However, none of these known sources produce the distinctive metabolites present in the tapestry. LC-qToF-MS was also used to compare the chemical composition of the dyes in the tapestry with that of several species of crustose lichen. Lichen metabolites, including thiophanic acid and arthothelin, were definitively identified in the tapestry based on comparison with lichen xanthone standards and a reference of Lecanora sulphurata, confirming the presence of a lichen source. This finding marks the first time that lichen xanthones have been identified in a historic object and the first evidence that BWM lichen dyes may have been used prior to the eighteenth century.

The search for effective antidiabetic agents, both synthetic and natural, has intensified over the years. This review provides a comprehensive examination of xanthone compounds as potential antidiabetic agents, exploring their sources, chemical structures, and pharmacological properties. Xanthones have been shown to enhance insulin sensitivity, modulate glucose metabolism, and mitigate oxidative stress and inflammation through various mechanisms. Key molecular targets include AMP-activated protein kinase (AMPK), peroxisome proliferator-activated receptors (PPARs), α-amylase, and α-glucosidase.The review details in vitro studies demonstrating that xanthones like γ-mangostin and mangiferin inhibit α-amylase and α-glucosidase with IC50 values of 3.2 μM and 5.6 μM, respectively, highlighting their potential to improve glucose metabolism. In vivo studies have shown that xanthones improve glucose homeostasis, lipid profiles, and overall glycemic control in diabetic models. For instance, mangiferin administration in streptozotocin-induced diabetic rats resulted in lower fasting blood glucose levels and improved HDL levels.Moreover, the safety profile and potential side effects associated with xanthone usage are discussed, providing a balanced view of their therapeutic potential. This review consolidates current knowledge on xanthones' antidiabetic properties and serves as a valuable resource for further research and development of these compounds as antidiabetic agents.

As part of a long-term campaign to document, study, and conserve the Heroes tapestries from The Cloisters collection at The Metropolitan Museum of Art, organic colorant analysis of Julius Caesar (accession number 47.101.3) was performed. Analysis with liquid chromatography–quadrupole time-of-flight mass spectrometry (LC-qToF-MS) revealed the presence of several multiply chlorinated xanthones produced only by certain species of lichen. Various lichen dye sources have been documented in the literature for centuries and are classified as either ammonia fermentation method (AFM) or boiling water method (BWM) dyes based on their method of production. However, none of these known sources produce the distinctive metabolites present in the tapestry. LC-qToF-MS was also used to compare the chemical composition of the dyes in the tapestry with that of several species of crustose lichen. Lichen metabolites, including thiophanic acid and arthothelin, were definitively identified in the tapestry based on comparison with lichen xanthone standards and a reference of Lecanora sulphurata, confirming the presence of a lichen source. This finding marks the first time that lichen xanthones have been identified in a historic object and the first evidence that BWM lichen dyes may have been used prior to the eighteenth century. [ABSTRACT FROM AUTHOR]

Tyrosinase inhibitors can reduce melanin production for skin whitening, but some existing products may harm the skin. This study discovered six compounds that inhibit tyrosinase in the mushroom Agaricus bisporus by over 50%. Compound 11 displayed strong inhibition (92.2% and 86.7%) for L-tyrosine and L-DOPA substrates, while compound 13 showed high inhibition (96.0% and 62.0%) for both substrates. Molecular docking simulations revealed compounds 11 and 13 bind at the allosteric site of the enzyme. Xanthone derivatives, based on these findings, hold potential as safe skin whitening agents and for pigmentation-related diseases in the cosmetic industry. [ABSTRACT FROM AUTHOR]

A four‐step synthetic process has been developed to prepare 1,3,5,8‐tetrahydroxyxanthone (2a) and its isomer 1,3,7,8‐tetrahydroxyxanthone (2b). 25 more xanthones were also synthesized by a modified scheme. Xanthone 2a was identified as the most active inhibitor against both α‐glucosidase and aldose reductase (ALR2), with IC50 values of 7.8 ± 0.5 μM and 63.2 ± 0.6 nM, respectively, which was far active than acarbose (35.0 ± 0.1 μM), and a little more active than epalrestat (67.0 ± 3.0 nM). 2a was also confirmed as the most active antioxidant in vitro with EC50 value of 8.9 ± 0.1 μM. Any structural modification including methylation, deletion, and position change of hydroxyl group in 2a will cause an activity loss in inhibitory and antioxidation. By applying a H2O2‐induced oxidative stress nematode model, it was confirmed that xanthone 2a can be absorbed by Caenorhabditis elegans and is bioavailable to attenuate in vivo oxidative stress, including the effects on lifespan, superoxide dismutase, Catalase, and malondialdehyde. 2a was verified with in vivo hypoglycemic effect and mitigation of embryo malformations in high glucose. All our data support that xanthone 2a behaves triple roles and is a potential agent to treat diabetic mellitus, gestational diabetes mellitus, and diabetic complications. [ABSTRACT FROM AUTHOR]

Genus Calophyllum is well-known for its phenolic constituents, especially coumarins, which have shown to have a wide range of significant biological activities. In this study, four known phenolic constituents and two triterpenoids have been isolated from the stem bark of Calophyllum lanigerum. The compounds were two pyranochromanone acids are known as caloteysmannic acid (1), isocalolongic acid (2), a simple dihydroxyxanthone, namely euxanthone (3), one coumarin named calanone (4), and two common triterpenoids, friedelin (5), and stigmasterol (6). Chromanone acids were reported for the first time in this Calophyllum species. Cytotoxic evaluations were carried out on n-hexane extract (87.14 ± 2.04 µg/mL; 81.46 ± 2.42 µg/mL) followed by the chromanone acids (1 [79.96 ± 2.39 µM; 83.41 ± 3.39 µM] & 2 [57.88 ± 2.34; 53.04 ± 3.18 µM]) against two cancerous cell lines, MDA-MB-231 and MG-63 cell lines, respectively. The results showed that all tested samples exhibited moderate cytotoxicity. [ABSTRACT FROM AUTHOR]

Spectroscopic studies were carried out for the interaction of the bioactive compounds 2,3-dimethoxyxanthone (1) and 3,4-dimethoxyxanthone (2) with human serum albumin (HSA). The UV absorption, steady-state, and time-resolved fluorescence spectroscopy studies showed that 1 and 2 interact with HSA through a ground-state association. The decrease in the Stern-Volmer constant (KSV) values with increasing temperature, and the bimolecular quenching rate constant (kq) values in the order of 1012 M−1s−1 indicated a static fluorescence quenching mechanism, corroborating with time-resolved fluorescence decays. The association constant (Ka) values in the order of 104 M−1 indicated a moderate interaction between these xanthones and HSA. Circular dichroism experiments showed weak perturbation on the secondary structure of albumin after the interaction with 1 and 2. Thermodynamic parameters suggested that the binding is entropically (for HSA:1, ΔS° 0.012 ± 0.003 and for HSA:2 0.008 ± 0.002 J/molK) and enthalpically (for HSA:1, ΔH° -24.0 ± 0.99 and for HSA:2 -25.6 ± 0.67 kJ/mol) controlled, with a Gibbs free energy change (ΔG°) close to -28.0 kJ/mol in both cases. Competitive drug-displacement and molecular docking results showed that 1 and 2 could interact not only with subdomain IIA, where Trp-214 residue can be found, but also with subdomains IIIA and IB. Hydrogen bonding, electrostatic, and hydrophobic interactions were detected as the main binding forces to stabilize the association HSA:1 and HSA:2. Overall, the dimethoxyxanthones have similar binding affinity compared with highly oxygenated xanthones, e.g., mangiferin, gentiacaulein, and norswertianin.

Xanthones are chemical substances in higher plants, marine organisms, and lower microorganisms. The most prevalent naturally occurring sources of xanthones are those belonging to the families Caryophyllaceae, Guttiferae, and Gentianaceae. Structurally, xanthones (9H xanthan-9-one) are heterocyclic compounds with oxygen and a γ-pyrone component. They are densely packed with a two-benzene ring structure. The carbons in xanthones are numbered from their nucleus and biosynthetic construct. They have mixed shikimate-acetate (higher plants) and acetate-malonate (lower organisms) biosynthetic origins, which influence their classification. Based on the level of oxidation of the C-ring, they are classified into monomers, dimers, and heterodimers. While based on the level of oxygenation or the type of ring residue, they can be categorized into mono-, di-, tri-, tetra-, penta- and hexa-oxygenated xanthones, bis-xanthones, prenylated and related xanthones, xanthonolignoids, and other miscellaneous xanthones. This structural diversity has made xanthones exhibit considerable biological properties as promising antioxidant, antifungal, antimicrobial, and anticancer agents. Structure-activity relationship studies suggest C-1, C-3, C-6, and C-8 as the key positions that influence the biological activity of xanthones. Furthermore, the presence of functional groups, such as prenyl, hydroxyl, glycosyl, furan, and pyran, at the key positions of xanthones, may contribute to their spectrum of biological activity. The unique chemical scaffolds of xanthones, their notable biological activities, and the structure–activity relationships of some lead molecules were discussed to identify lead molecules as possible drug candidates.

Global health faces a significant issue with the rise of infectious diseases caused by bacteria, fungi, viruses, and parasites. The increasing number of multi-drug resistant microbial pathogens severely threatens public health worldwide. Antibiotic-resistant pathogenic bacteria, in particular, present a significant challenge. Therefore, there is an urgent need to identify new potential antimicrobial targets and discover new chemical entities that can potentially reverse bacterial resistance. The main goal of this research work was to create and develop a library of 3,6-disubstituted xanthones based on twin drugs and molecular extension approaches to inhibit the activity of efflux pumps. The process involved synthesizing 3,6-diaminoxanthones through the reaction of 9-oxo-9H-xanthene-3,6-diyl bis(trifluoromethanesulfonate) with various primary and secondary amines. The resulting 3,6-disubstituted xanthone derivatives were then tested for their in vitro antimicrobial properties against a range of pathogenic strains and their efficacy in inhibiting the activity of efflux pumps, biofilm formation, and quorum-sensing. Several compounds have exhibited effective antibacterial properties against the Gram-positive bacterial species tested. Xanthone 16, in particular, has demonstrated exceptional efficacy with a remarkable MIC of 11 µM (4 µg/mL) against reference strains Staphylococcus aureus ATCC 25923 and Enterococcus faecalis ATCC 29212, and 25 µM (9 µg/mL) against methicillin-resistant S. aureus 272123. Furthermore, some derivatives have shown potential as antibiofilm agents in a crystal violet assay. The ethidium bromide accumulation assay pinpointed certain compounds inhibiting bacterial efflux pumps. The cytotoxic effect of the most promising compounds was examined in mouse fibroblast cell line NIH/3T3, and two monoamine substituted xanthone derivatives with a hydroxyl substituent did not exhibit any cytotoxicity. Overall, the nature of the substituent was critical in determining the antimicrobial spectra of aminated xanthones. [ABSTRACT FROM AUTHOR]

Hairy root (HR) cultures of Hypericum perforatum L. have shown promise in controlling hyperglycemia, regulating blood lipid and enzyme profiles, and improving metabolic function in vivo. These benefits are mainly attributed to the phenolic acids, flavonoids, and xanthones present in HR extracts. However, the specific mechanism underlying these effects remains unclear. This study was performed to elucidate the biochemical and molecular mechanisms driving HR the antihyperglycemic and antidiabetic effects of HR extracts. HR extract (200 mg/kg body weight) was administered daily for 14 days to healthy rats and rats with streptozotocin-induced diabetes, with glibenclamide serving as a positive control. The phenolic composition of the HR extracts was confirmed through high-performance liquid chromatography/diode array detection/electrospray ionization mass spectrometry (HPLC/DAD/ESI-MSn ) analysis. The results showed that HR extract treatment increased the plasma insulin level and pancreatic poly (adenosine diphosphate-ribose) polymerase (PARP) activity in diabetic rats, thus normalizing blood glucose levels. Additionally, it reduced the activity of gluconeogenic enzymes, increased the activity of glycolytic enzymes, and normalized the glycogen content in the liver. HR extract-treated rats also exhibited increased hepatic adenosine monophosphate-activated protein kinase (AMPK) mRNA expression and a decreased protein kinase Cε (PKCε) concentration. In conclusion, HR extract demonstrated insulinotropic effects and effectively regulated hepatic carbohydrate metabolism in diabetic rats by modulating AMPK expression and the PKCε concentration. These findings suggest the potential use of HR extract as an herbal medicine for diabetes treatment and a source of antidiabetic drug development. [ABSTRACT FROM AUTHOR]

A validated UHPLC-HRMS method was developed to identify and quantify polar phenolic metabolites in the EtOH extract from H. aucheri Jaub. & Spach's aerial parts. The external standards, chlorogenic acid, mangiferin, and hyperoside were selected in this analysis. Forty-four compounds, encompassing hydroxybenzoic and hydroxycinnamic acids derivatives, benzophenones, catechins, xanthones, flavonols, biflavones, and chromones were detected and quantified in the aerial parts of the titled plant. Pentahydroxyxanthone-C-glycoside 15, maclurin-O-(benzoyl)-hexoside 37, norathyriol-O-(benzoyl)-hexosides 38 and 42 were suggested to be new natural compounds, while maclurin-O-hexoside 2 was reported for the first time for Hypericum genus. Additionally, more than 22 secondary metabolites, including benzophenones, hydroxycinnamic acid derivatives, catechins, and a chromone, were identified for the first time in H. aucheri. The amounts of the detected metabolites were calculated relative to external standards. The dominant polar phenolic constituents were chlorogenic acid (11.55 mg/g D.W.) and mangiferin (9.13 mg/g D.W.). [ABSTRACT FROM AUTHOR]

Phenolic compounds are known to degrade and/or undergo changes during food production and storage. Reaction kinetic modeling is generally used to define kinetic parameters of a food system and predict changes during thermal processing and storage. Data for phenolic acids and flavonoids, such as anthocyanins and flavan-3-ols, have been reviewed in detail, but the flavonoid sub-classes, dihydrochalcones and flavanones, have been mostly neglected. Other neglected phenolic classes are xanthones and benzophenones. The stability of these types of compounds is important as they are present in fruits and exposed to heat when processed into juice and jam. Other sources of the compounds are herbal teas, which are also subjected to thermal processing, either during the primary processing of the plant material, or the production of extracts for use as food ingredients. The theoretical background is given to understand the review of literature on these classes/sub-classes. Results of research on kinetic modeling are discussed in detail, while research on compound stability without the application of reaction kinetic modeling is briefly mentioned to provide context. The studies discussed included those focusing on heating during the processing and storage of model solutions, liquid foods, plant material, dried extracts, and extracts formulated with other food ingredients. [ABSTRACT FROM AUTHOR]

• Data was acquired from Pedro & group for preparation. • Discovery studio was used to prepare descriptors, combining DFT and MM. • A QSAR model was constructed using MLR in MS-Excel to establish the structure-activity relationship. • Rigorous internal and external validation ensured model accuracy. • DFT calculations, particularly on Mol 8 related to AD, and docking studies identified critical targets. Xanthone compounds are known to have diverse pharmacological activities, including anti-inflammatory, anticancer properties. However, they face challenges such as poor water solubility and a tendency to convert into phase 2 conjugates. Therefore, new strategies are needed to develop improved derivatives. Thus, this study aims to establish a mathematical 2D-QSAR model to predict the pGI 50 values of potential xanthone derivatives against breast cancer. For this study, the anti-breast cancer activity (pGI 50) values of 27 xanthone derivatives tested against MCF-7 cell lines were retrieved from the National Cancer Institute (NCI) data library. Regression analysis was performed using various physiochemical and Density Functional Theory (DFT)–based descriptors to model a 2D-QSAR equation. The model was internally and externally validated, and the most reactive xanthone derivatives were identified. Based on the QSAR equation, 10 new molecules were computationally designed, and their pGI 50 values were determined. The applicability domain (AD) was defined, and the Y-randomization test confirmed the validity and reliability of the QSAR model. DFT calculations were carried out for these molecules, of which Mol 1, Mol 2, Mol 8, and Mol 10 exhibited high reactivity. However, it was found that only Mol 8 fell within the AD, making it suitable for further investigation through molecular docking studies involving cancer proteins. During the molecular docking analyses, the binding energy and interactions between Mol 8 and the target proteins were evaluated. The results showed that Mol 8 exhibited superior binding energy and interactions compared to the native ligands. Additionally, Mol 8 demonstrated more favorable ADMET properties than the native ligands. These findings suggest that Mol 8 holds promise for designing novel and more potent compounds due to its advantageous characteristics and interactions with the target proteins. [ABSTRACT FROM AUTHOR]

This article provides a detailed exploration of the synthesis of symmetrical xanthones, which are oxygen-containing heterocycles found in natural compounds and pharmaceuticals. The authors present their own method for synthesizing xanthones through a palladium-catalyzed carbonylative homocoupling reaction of 2-iodophenols. They found that the optimal reaction conditions were Pd(OAc)2 as a catalyst, Cs2CO3 as a base, and DMSO as a solvent at 100 °C. The study also examines the synthesis of other derivatives using variations of the reaction conditions. The article includes a table showing the results of different reaction parameters and provides a proposed mechanistic pathway for the xanthone synthesis. [Extracted from the article]

The changes in the composition and content of phenolic compounds in the leaves and inflorescences of Hedysarum alpinum L. and H. flavescens Regel et Schmalh., introduced into the forest-steppe zone of Western Siberia, were studied. Using the example of H. alpinum, the variation in the content of phenolic compounds depending on the year of harvest and on the plant organ (leaves, inflorescences) was investigated. The contents of individual substances (gallic acid, chlorogenic acid, mangiferin, hyperoside, rutin, avicularin, and 17 phenolic components) and of phenolic compounds by groups (hydroxycinnamic acids, hydroxybenzoic acids, xanthones, and flavonols) were determined. Differences in the content of phenolic compounds by groups (in mg/100 g) were found between the two species of the genus Hedysarum L. Specifically, the leaves of H. alpinum accumulated more xanthones and flavonols (up to 4614.9 ± 63.7 and 1280.0 ± 6.7, respectively) and the inflorescences, more xanthones (up to 847.9 ± 29.8) compared to the leaves (2911.6 ± 79.0 and 976.2 ± 0.5, respectively) and the inflorescences (76.2 ± 2.5) of H. flavescens. In the leaves of H. flavescens, compared to the leaves of H. alpinum, the content of hydroxybenzoic acids and hydroxycinnamic acids prevailed. The leaves of the studied species accumulated mostly hydroxycinnamic acids and xanthones, and the inflorescences, mostly flavonols. The contents of hydroxybenzoic acids, xanthones, and flavonols in H. alpinum varied significantly depending on the year of observation. [ABSTRACT FROM AUTHOR]

This article discusses the application of the Heck reaction for the synthesis of C-glycosyl phenolic compounds. The authors successfully synthesized C-glycosylated 2-styrylchromones and xanthones with high stereoselectivity. The article also includes detailed experimental procedures and characterization data for the synthesized compounds. The given text appears to be a scientific article or research paper that includes data related to chemical compounds. The text provides information about the chemical structure and properties of different compounds, including their nuclear magnetic resonance (NMR) spectra, mass spectrometry data, and physical characteristics. The compounds mentioned in the text are described in terms of their chemical composition, yield, and various spectroscopic data. [Extracted from the article]

In order to improve naturally occurring xanthones’ anticancer properties, chemical synthesis is proposed. In this study, from eight novel xanthone derivatives coupled to morpholine or aminoalkyl morpholine, only the two most active ones were chosen. For additional enhancement of the anticancer activity of our tested compounds, we combined chemotherapy with hyperthermia in the range of 39–41 °C, from which the mild conditions of 39 °C were the most influencing. This approach had a profound impact on the anticancer properties of the tested compounds. TOV-21G and SC-OV-3 ovarian cell line motility and metastasis behavior were tested in native and hyperthermia conditions, indicating decreased wound healing properties and clonogenic activity. Similarly, the expression of genes involved in metastasis was hampered. The expression of heat shock proteins involved in cancer progression (Hsc70, HSP90A, and HSP90B) was significantly influenced by xanthone derivatives. Chemotherapy in mild hyperthermia conditions had also an impact on decreasing mitochondria potential, visualized with JC-1. Synthetic xanthone ring modifications may increase the anticancer activity of the obtained substances. Additional improvement of their activity can be achieved by applying mild hyperthermia conditions. Further development of a combined anticancer therapy approach may result in increasing currently known chemotherapeutics, resulting in a greater recovery rate and diminishment of the cytotoxicity of drugs.

Despite the existence of various therapeutic approaches, diabetes mellitus and its complications have been an increasing burden of mortality and disability globally. Hence, it is necessary to evaluate the efficacy and safety of medicinal plants to support existing drugs in treating diabetes. Xanthones, the main secondary metabolites found in Gentiana dinarica and Gentiana utriculosa, display various biological activities. In in vitro cultured and particularly in genetically transformed G. dinarica and G. utriculosa roots, there is a higher content of xanthones. The aim of this study was to investigate and compare antidiabetic properties of secondary metabolites (extracts) prepared from these two Gentiana species, cultured in vitro and genetically transformed with those collected from nature. We compare HPLC secondary metabolite profiles and the content of the main extract compounds of G. dinarica and G. utriculosa methanol extracts with their ability to scavenge DPPH free radicals and inhibit intestinal α-glucosidase in vitro. Anti-hyperglycemic activity of selected extracts was tested further in vivo on glucose-loaded Wistar rats. Our findings reveal that the most prominent radical scavenging potential and potential to control the rise in glucose level, detected in xanthone-rich extracts, were in direct correlation with an accumulation of xanthones norswertianin and norswertianin-1-O-primeveroside in G. dinarica and decussatin and decussatin-1-O-primeveroside in G. utriculosa.

Hypericum beanii N. Robson, a perennial upright herb, predominantly inhabits temperate regions. This species has been utilized for the treatment of various inflammation-related diseases. One new xanthone 3,7-dihydroxy-1,6-dimethoxyxanthone (1) and twenty-three known xanthones (2–24) were isolated from the aerial parts of H. beanii. The structure of the new compound was determined based on high-resolution electrospray ionization mass spectroscopy (HR-ESIMS), nuclear magnetic resonance (NMR), Infrared Spectroscopy (IR), ultraviolet spectrophotometry (UV) spectroscopic data. The anti-inflammatory effects of all the isolates were assessed by measuring the inhibitory effect on nitric oxide (NO) production in LPS-stimulated RAW 264.7 macrophages. Compounds 3,4-dihydroxy-2-methoxyxanthone (15), 1,3,5,6-tetrahydroxyxanthone (19), and 1,3,6,7-tetrahydroxyxanthone (22) exhibited significant anti-inflammatory effects at a concentration of 10 μM with higher potency compared to the positive control quercetin. Furthermore, compounds 15, 19, and 22 reduced inducible NO synthase (iNOS), tumor necrosis factor alpha (TNF-α), interleukin-1β (IL-1β), IL-6, and cyclooxygenase 2 (COX-2) mRNA expression in the LPS-stimulated RAW 264.7 macrophages, suggesting that these compounds may mitigate the synthesis of the aforementioned molecules at the transcriptional level, provisionally confirming their anti-inflammatory efficacy.

Benzylic systems such as 9H-xanthenes, 9H-thioxanthenes and 9,10-dihydroacridines can be easily oxidized to the corresponding xanthones, thioxanthones or acridones, respectively, in deep eutectic solvents by a visible blue light-promoted photooxidation procedure carried out using ambient air as oxidant in the presence of riboflavin tetraacetate as a metal-free photocatalyst. The obtained yields are high or almost quantitative, and the reaction media can be recovered and reused. The environmental friendliness of the protocol is demonstrated based on several green metrics.

Garcinia livingstonei T. Anderson, also referred to as African or Lowveld mangosteen, is a medicinal plant belonging to the Clusiaceae family and is used in traditional medicine to treat variety of diseases including diabetes, parasitic infections, microbial infections, and other ailments. This review provides an overview of this medicinal plant by highlighting its traditional applications, phytochemical properties, pharmacological activities, and toxicity, in addition to offering guidance for future G. livingstonei studies. These bioactivities include antimicrobial, antioxidant, antiparasitic, antiviral, and antiproliferative activities. The findings of this work reveal that the pharmacological activities of G. livingstonei crude extracts and bioactive compounds confirm the diversified use, and the effectiveness of G. livingstonei leaves, stem, bark, and fruits in the traditional remedies of many diseases. To date, about 38 secondary metabolites have been isolated from the different parts of this plant, with xanthones and biflavonoids being particularly prominent. Pharmacological and chemical research suggests that G. livingstonei contains a variety of bioactive compounds, which is worthy of comprehensive and in-depth research. Nevertheless, animal toxicological examinations and efficacy studies are still required to conclusively validate the traditional uses and in vitro pharmacological activities. [Display omitted] • Garcinia livingstonei is used in traditionally to treat variety of diseases in South Africa and other African countries. • G. livingstonei has antioxidant, antimicrobial, antioxidant, antiparasitic, antiviral, and antiproliferative activities. • About 38 secondary metabolites have been isolated from the plant, with xanthones and biflavonoids being particularly prominent. • Further studies should focus on in vivo studies. [ABSTRACT FROM AUTHOR]

Nuclear factor erythroid 2-related factor 2 (Nrf2) pathway activation promotes the expression of antioxidant enzymes in response to rising oxidative stress, resulting in reactive oxygen species (ROS) detoxification and playing a central role in the maintenance of intracellular redox homeostasis and regulation of inflammation. Moreover, the biological effects of Nrf2 pathway activation contribute to reducing apoptosis and enhancing cell survival. The activity of Nrf2 is negatively regulated by Kelch-like ECH-associated protein 1 (Keap1). Prompted by the recent results reporting the impact of xanthone metabolites on oxidative stress, cancer, and inflammation, the antioxidant properties of xanthones isolated from Garcinia mangostana (γ-mangostin, α-mangostin, 8-deoxygartanin, demethylcalabaxanthone, garcinone D) were assessed. In particular, the capability of these natural products to disrupt the interaction between Kelch-like ECH-associated protein 1 (Keap1) and nuclear factor erythroid 2-related factor 2 (Nrf2), triggering the activation of the Nrf2-mediated pathway, was evaluated using molecular docking experiments and in vitro tests. The modulation of some key Nrf2-related mediators like glutathione (GSH) and lactate dehydrogenase (LDH) to highlight a possible direct antioxidant effect was investigated. Among the tested compounds, demethylcalabaxanthone showed an indirect antioxidant effect, as corroborated by a Western blot assay, displaying a significant increase in the translocated protein upon its administration. [ABSTRACT FROM AUTHOR]

α-Mangostin, a major xanthone found in mangosteen (Garcinia mangostana L., Family Clusiaceae) pericarp, has been shown to exhibit anticancer effects through multiple mechanisms of action. However, its effects on immune checkpoint programmed death ligand-1 (PD-L1) have not been studied. This study investigated the effects of mangosteen pericarp extract and its active compound α-mangostin on PD-L1 by in vitro and in silico analyses. HPLC analysis showed that α-mangostin contained about 30% w/w of crude ethanol extract of mangosteen pericarp. In vitro experiments in MDA-MB-231 triple-negative breast cancer cells showed that α-mangostin and the ethanol extract significantly inhibit PD-L1 expression when treated for 72 h with 10 µM or 10 µg/mL, respectively, and partially inhibit glycosylation of PD-L1 when compared to untreated controls. In silico analysis revealed that α-mangostin effectively binds inside PD-L1 dimer pockets and that the complex was stable throughout the 100 ns simulation, suggesting that α-mangostin stabilized the dimer form that could potentially lead to degradation of PD-L1. The ADMET prediction showed that α-mangostin is lipophilic and has high plasma protein binding, suggesting its greater distribution to tissues and its ability to penetrate adipose tissue such as breast cancer. These findings suggest that α-mangostin-rich mangosteen pericarp extract could potentially be applied as a functional ingredient for cancer chemoprevention. [ABSTRACT FROM AUTHOR]

Mammea siamensis (Miq.) T. Anders. (Calophyllaceae) plants have long been employed as an active integral composition in Thai traditional medicine. Additionally, phenylcoumarins and triterpenes were reported as major components in phytochemical research. This work explored the various parts of M. siamensis; barks, flowers, twigs, leaves, and young leaves; to determine their bioactive compounds. By using the GC-MS and bioassay guidance, two xanthones, 6-deoxyisojacareubin (1) and 1,5-dihydroxyxanthone (2), together with a mixture of phenylcoumarins, mammea A/AA cyclo D (3) and mammea A/AB cyclo D (4) have been isolated from the methanolic extract of young leaves. Their structures were identified by means of spectroscopic technique and by comparison with literature data. In particular, the current study was the first exposed report of xanthones 1 and 2 from the genus Mammea. Furthermore, compounds 1 and 2 and the methanolic young leaf extract had high antioxidant efficiency on DPPH and ABTS assays. The young leaf extract provided mild toxicity on the brine shrimp lethality test (BSLT) with LC50 value of 93.11 ± 1.37 µg/mL. In addition, the isolated compounds 1 and 2 were non-toxicity in BSLT assay. Therefore, the young leaf extract and the purified constituents 1 and 2 should be further studied and developed for using in pharmaceutical industries.

Chemical and natural toxic compounds can harm human health through a variety of mechanisms. Nowadays, herbal therapy is widely accepted as a safe method of treating toxicity. Garcinia mangostana (mangosteen) is a tree in the Clusiaceae family, and isoprenylated xanthones, its main constituents, are a class of secondary metabolites having a variety of biological properties, such as anti-inflammatory, anti-oxidant, pro-apoptotic, anti-proliferative, antinociceptive, neuroprotective, hypoglycemic, and anti-obesity. In this review, the protective activities of mangosteen and its major components against natural and chemical toxicities in both in vivo and in vitro experiments were evaluated. The protective effects of mangosteen and its components are mediated primarily through oxidative stress inhibition, a decrease in the number of inflammatory cells such as lymphocytes, neutrophils, and eosinophils, reduction of inflammatory mediators such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), interleukin-6 (IL-6), interleukin-8 (IL-8), cyclooxygenase-2 (COX-2), prostaglandin (PG) E2, inducible nitric oxide synthase, and nuclear factor-ĸB (NF-ĸB), modulation of apoptosis and mitogen-activated protein kinase (MAPK) signaling pathways, reducing p65 entrance into the nucleus, α-smooth muscle actin (α-SMA), transforming growth factor β1 (TGFβ1), improving histological conditions, and inhibition in acetylcholinesterase activity.

Psorospermum febrifugum Spach is widely used in traditional African medicinal care for ailments such as malarial, pneumonia, skin disease, dysmenorrhoea, dysentery, tuberculosis, etc.. This review presents ethnomedicinal uses, phytochemical composition, pharmacological activities and toxicology of P. febrifugum for the first time. This is with a view to appraise the extent to which the plant has been explored in ethnomedicinal care and to identify the knowledge gap to spur future research into evaluating its pharmacological activities, mechanism actions and toxicological effects of extracts and isolated compounds. Information on the distribution, morphology, folkloric/traditional uses, ethnomedicine, phytochemistry and pharmacology was gathered from online scientific databases such as Google Scholar, PubMed, Science Direct, and relevant online books and sources from 1953 to 2023. Pharmacological data from in vitro and in vivo studies revealed that P. febrifugum metabolites and extracts possess biological activities such as antioxidant, antimicrobial, anticancer, acaricidal, anxiolytic, antipsoriatic, antimalarial, antitrypanosomal activity, and anti-inflammatory, which confirmed the folkloric usages of the plant. Regarding the phytochemistry of the plant, anthraquinones and xanthones are the most isolated metabolites from P. febrifugum roots and fruits, and they have been confirmed to have anticancer properties.Toxicological studies on the extracts from the plant also revealed the plant is safe for oral administration. Future studies on the therapeutic potentials of P. febrifugum should focus on clinical trials and pharmacological studies of the extract that have only been tested in vitro to harness the medicinal properties of P. febrifugum fully. The plant's leaves must also be screened for critical therapeutic metabolites, as most of the reported studies on the phytochemistry of P. febrifugum have focused on barks, stems and roots.

Four new xanthones, cratocochinones A–D (1–4), together with eight known analogues (5–12), were isolated from the stems and leaves of Cratoxylum cochinchinense. The chemical structures of cratocochinones A–D (1–4) were elucidated by comprehensive spectroscopic analyses and the known compounds were identified by comparisons with the spectral data reported in the literature. All isolated compounds 1–12 were evaluated for their anti-inflammatory activities and anti-HIV-1 activities. Compounds 1–12 showed remarkable inhibitory activities on nitric oxide (NO) production induced by lipopolysaccharide in mouse macrophage RAW 264.7 cells in vitro, with IC50 values in the range of 0.86 ± 0.05 to 18.36 ± 0.21 µM. Meanwhile, compounds 1–12 exhibited significant anti-HIV-1 activities with EC50 which ranged from 0.22 to 11.23 µM. These findings indicate that the discoveries of these xanthones, isolated from the stems and leaves of C. cochinchinense, showing significant anti-inflammatory and anti-HIV-1 effects could be of great importance to the research and development of new natural anti-inflammatory and anti-HIV agents. [ABSTRACT FROM AUTHOR]

The chemical investigation of Homotrigona apicalis propolis collected in Binh Dinh province, Vietnam, led to the isolation of nine compounds, including four sesquiterpenes: spathulenol (1), 1αH,5βH-aromandendrane-4β,10α-diol (2), 1β,6α-dihydroxy-4(15)-eudesmene (3), and 1βH,5βH-aromandendrane-4α,10β-diol (4); three triterpenes: acetyl oleanolic acid (5), 3α-hydroxytirucalla-8,24-dien-21-oic acid (6), and ursolic acid (7); and two xanthones: cochinchinone A (8) and α-mangostin (9). Sesquiterpens 1–4 and triterpene 6 were isolated for the first time from stingless bee propolis. Plants in the Cratoxylum and Aglaia genus were suggested as resin sources of the propolis sample. In the antibacterial activity evaluation, the EtOH extract only showed moderate activity on S. aureus, while the isolated compounds 7–9 showed good antibacterial activity, with IC50 values of 0.56 to 17.33 µg/mL. The EtOH extract displayed selective cytotoxicity against the A-549 cancer cell line, with IC50 values of 22.82 ± 0.86 µg/mL, and the xanthones 8 and 9 exhibited good activity against the KB, HepG-2, and A-549 cancer cell lines, with IC50 values ranging from 7.55 ± 0.25 µg/mL to 29.27 ± 2.07 µg/mL. The cytotoxic effects of xanthones 8 and 9 were determined by the inhibition of the EGFR and HER2 pathways using a molecular docking study. Compounds 8 and 9 displayed strong binding affinity with EFGR and HER2, with values of −9.3 to −9.9 kcal/mol. Compounds 5, 8, and 9 showed potential α-glucosidase inhibitory activities, which were further confirmed by computational studies. The binding energies of compounds 5, 8, and 9 were lower than that of arcabose. [ABSTRACT FROM AUTHOR]

Two new xanthones, oblongixanthones I (1) and J (2), and seven known compounds (3–9), were isolated from an EtOAc extract of the twigs of Garcinia oblongifolia. Their structures were elucidated using spectroscopic methods, mainly 1 D and 2 D NMR. The antidiabetic effects of the two new compounds were evaluated using α-glucosidase and PTP1B inhibition assays. Both compounds displayed strong inhibition towards α-glucosidase with IC50 values of 258.7 ± 49.3 and 187.1 ± 27.5 μM, respectively (compared with acarbose, IC50 = 900.0 ± 3.0 μM) and moderate effects against PTP1B with IC50 values of 93.9 ± 12.3 and 64.1 ± 5.8 μM, respectively (compared with RK682, IC50 = 4.4 ± 0.3 l μM). [ABSTRACT FROM AUTHOR]

Phytochemical profiling of six natural populations of Gentianella austriaca was performed by HPLC identification and quantification of a number of secondary metabolites, and evaluation of time series of peak areas by chemometric analysis. Phytochemical analysis of G. austriaca revealed the presence of iridoids, flavone-C-glucosides and xanthones. Twelve secondary metabolites were identified in the aerial parts, roots and seeds, including swertiamarin (SWM), gentiopicrin (GP), sweroside (SWZ), isoorientin (ISOOR), swertisin (SWE), demethylbellidifolin-8-O-glucoside (DMB-8-O-glc), bellidifolin-8-O-glucoside (BDF-8-O-glc), mangiferin (MGF), corymbiferin (CBF), corymbiferin-1-O-glucoside (CBF-1-O-glc), bellidifolin (BDF) and campestroside. Multivariate statistical analyses showed relatively low variability among populations according to secondary metabolite content. However, some pharmacologically important compounds were found in higher amounts in a few populations, which could be useful for conservation and future biotechnological procedures. [ABSTRACT FROM AUTHOR]

Instruction: Hypericum bellum Li is rich in xanthones with various bioactivities, especially in anti‐breast cancer. While the scarcity of mass spectral data of xanthones in Global Natural Products Social Molecular Networking (GNPS) libraries have challenged the rapid recognition of xanthones with similar structures. Objective: This study is aimed to enhance the molecular networking (MN)‐based dereplication and visualisation ability of potential anti‐breast cancer xanthones from H. bellum to overcome the scarcity of xanthones mass spectral data in GNPS libraries. Separating and purifying the MN‐screening bioactive xanthones to verify the practicality and accuracy of this rapid recognition strategy. Methodology: A combined strategy of "seed" mass spectra‐based MN, in silico annotation tools, substructure identification tools, reverse molecular docking, ADMET screening, molecular dynamics (MDs) simulation experiments, and an MN‐oriented separation procedure was first introduced to facilitate the rapid recognition and targeted isolation of potential anti‐breast cancer xanthones in H. bellum. Results: A total of 41 xanthones could only be tentatively identified. Among them, eight xanthones were screened to have potential anti‐breast cancer activities, and six xanthones that were initially reported in H. bellum were obtained and verified to have good binding abilities with their paired targets. Conclusion: This is a successful case study that validated the application of "seed" mass spectral data could overcome the drawbacks of GNPS libraries with limited mass spectra and enhance the accuracy and visualisation of natural products (NPs) dereplication, and this rapid recognition and targeted isolation strategy can be also applicable for other types of NPs. A combined strategy of "seed" mass spectra‐based molecular networking (MN), in silico tandem mass spectrometry (MS/MS) fragmentation, reverse molecular docking, ADMET screening, and an MN‐oriented separation procedure was first introduced to facilitate the rapid recognition and targeted isolation of potential anti‐breast cancer xanthones in Hypericum bellum Li. As a result, a total of 41 xanthones could only be tentatively identified. Among them, six xanthones that were initially reported in H. bellum were targeted isolated. [ABSTRACT FROM AUTHOR]

In recent decades, the relationship between drug chirality and biological activity has been assuming enormous importance in medicinal chemistry. Particularly, chiral derivatives of xanthones (CDXs) have interesting biological activities, including enantioselective anti-inflammatory activity. Herein, the synthesis of a library of CDXs is described, by coupling a carboxyxanthone (1) with both enantiomers of proteinogenic amino esters as chiral building blocks (2–31), following the chiral pool strategy. The coupling reactions were performed at room temperature with good yields (from 44 to 99.9%) and very high enantiomeric purity, with most of them presenting an enantiomeric ratio close to 100%. To afford the respective amino acid derivatives (32–61), the ester group of the CDXs was hydrolyzed in mild alkaline conditions. Consequently, in this work, sixty new derivatives of CDXs were synthetized. The cytocompatibility and anti-inflammatory activity in the presence of M1 macrophages were studied for forty-four of the new synthesized CDXs. A significant decrease in the levels of a proinflammatory cytokine targeted in the treatment of several inflammatory diseases, namely interleukin 6 (IL-6), was achieved in the presence of many CDXs. The amino ester of L-tyrosine (X1AELT) was the most effective in reducing IL-6 production (52.2 ± 13.2%) by LPS-stimulated macrophages. Moreover, it was ≈1.2 times better than the D-enantiomer. Indeed, enantioselectivity was observed for the majority of the tested compounds. Thus, their evaluation as promising anti-inflammatory drugs should be considered. [ABSTRACT FROM AUTHOR]

Previous phytochemical investigations reported that Calophyllum spp have biosynthesized a wide range of bioactive phenolics such as xanthones and coumarins. The phytochemical study conducted on the stem bark of C. canum has led to the isolation of eight trioxygenated xanthones namely: 5-methoxytrapezifolixanthone (1), 5-methoxyananixanthone (2), caloxanthone C (3), 1,5-dihydroxy-3-methoxy-4-isoprenylxanthone (4), 6-deoxyisojacareubin (5), euxanthone (6), trapezifolixanthone (7), ananixanthone (8), together with three common triterpenoids, β-sitosterol (9), friedelin (10), and stigmasterol (11). Furthermore, xanthones 1 and 2 were isolated for the first time as naturally occurring xanthones from the plant extract. The structures of these compounds were identified and elucidated using advanced spectroscopic techniques such as 1 D & 2 D NMR, MS, and FTIR. The neuroprotective property of selected compounds was tested through in vitro stroke model. Among all tested compounds, 1 µm of compounds 8, 9, and 10 showed significant neuroprotective activity via reduction of apoptosis by ∼ 50%. [ABSTRACT FROM AUTHOR]

Marine biofouling pollution is a process that impacts ecosystems and the global economy. On the other hand, traditional antifouling (AF) marine coatings release persistent and toxic biocides that accumulate in sediments and aquatic organisms. To understand the putative impact on marine ecosystems of recently described and patented AF xanthones (xanthones 1 and 2), able to inhibit mussel settlement without acting as biocides, several in silico environmental fate predictions (bioaccumulation, biodegradation, and soil absorption) were calculated in this work. Subsequently, a degradation assay using treated seawater at different temperatures and light exposures was conducted for a period of 2 months to calculate their half-life (DT50). Xanthone 2 was found to be non-persistent (DT50 < 60 days) at 50 μM, contrary to xanthone 1 (DT50 > 60 days). To evaluate the efficacy of both xanthones as AF agents, they were blended into four polymeric-based coating systems: polyurethane- and polydimethylsiloxane (PDMS)-based marine paints, as well as room-temperature-vulcanizing PDMS- and acrylic-based coatings. Despite their low water solubility, xanthones 1 and 2 demonstrated suitable leaching behaviors after 45 days. Overall, the generated xanthone-based coatings were able to decrease the attachment of the Mytilus galloprovincialis larvae after 40 h. This proof-of-concept and environmental impact evaluation will contribute to the search for truly environmental-friendly AF alternatives. [ABSTRACT FROM AUTHOR]

Mangosteen (Garcinia mangostana L.) pericarp is a potential source of bioactive xanthones. These xanthones can exert anti-diabetic and anti-malarial effects by inhibiting the activity of protein tyrosine phosphatase 1B (PTP1B) and quinone reductase 2 (QR-2), respectively. Therefore, developing an effective method for extracting the xanthones in mangosteen pericarp is of great significance to the conversion of these bioactive xanthones into drugs and food additives that can prevent and relieve malaria and diabetes. To obtain more active xanthones from mangosteen pericarp, the conditions of five extraction methods were optimized, and their extraction rates were evaluated by UHPLC-QQQ/MS. Among these extraction methods, ball milling extraction (BME) displayed obvious advantages, which included shorter extraction time, improved yield, lower cost, as well as being an environmentally friendly process. The mangosteen pericarp extract acquired by BME also exhibited strong inhibitory activity against PTP1B and QR-2. Thus, the BME method that we established for the extraction of xanthones from the mangosteen pericarp could lay a good foundation for the industrial application of mangosteen in food and medicine. It may also be used as an effective extraction method for extracting bioactive substances from other food pericarps. [ABSTRACT FROM AUTHOR]

Gartanin, a 4-prenylated xanthone, has been identified from the purple mangosteen fruit as a potent growth inhibitor of various cancer cell lines, including prostate cancer. However, much of Gartanin's anticancer mechanism remains unknown. We have discovered that Gartanin docked onto the regulatory subunit of the precursor cell-expressed developmentally downregulated 8 (NEDD8)-activating enzyme (NAE) complex and next to the NEDD8 binding complex, which leads to inhibit NEDD8 conjugations to both Cullin1 and Ubc12 in prostate cancer cell lines and Ubc12 NEDDylation in an in vitro assay. The S phase kinase-associated protein (Skp2) and F-box and WD-repeat domain-containing 2 (FBXW2), the NEDD8 family members of E3 ubiqutin ligases, were also downregulated and upregulated by Gartainin, respectively. Knock-down of NEDD8 expression by short harpin (Sh) RNAs blocked or attenuated these effects of Gartainin. Finally, Gartanin demonstrated its ability to inhibit growth of prostate cancer lines via autophagy initiation. Our data support that Gartanin is a naturally occurring NEDDylation inhibitor and deserves further investigation for prostate cancer prevention and treatment.

Species from the Garcinia genus (Clusiaceae family) are used in the treatment of many diseases and metabolic disorders frequently associated with the oxidative stress. The characteristic metabolites found in this genus are xanthones and benzophenones, which have antioxidant properties, among relevant biological potentials. This review provides a specific vision about antioxidant activity of Garcinia species, reporting in vitro and in vivo assays, described from the last five years. The research about antioxidant properties of Garcinia species and their constituents can be directed in the development of new medicines and drugs.