Showing papers on "Xanthone published in 2019"

Structure revision of cryptosporioptides and determination of the genetic basis for dimeric xanthone biosynthesis in fungi.

Abstract: Three novel dimeric xanthones, cryptosporioptides A-C were isolated from Cryptosporiopsis sp. 8999 and their structures elucidated. Methylation of cryptosporioptide A gave a methyl ester with identical NMR data to cryptosporioptide, a compound previously reported to have been isolated from the same fungus. However, HRMS analysis revealed that cryptosporioptide is a symmetrical dimer, not a monomer as previously proposed, and the revised structure was elucidated by extensive NMR analysis. The genome of Cryptosporiopsis sp. 8999 was sequenced and the dimeric xanthone (dmx) biosynthetic gene cluster responsible for the production of the cryptosporioptides was identified. Gene disruption experiments identified a gene (dmxR5) encoding a cytochrome P450 oxygenase as being responsible for the dimerisation step late in the biosynthetic pathway. Disruption of dmxR5 led to the isolation of novel monomeric xanthones. Cryptosporioptide B and C feature an unusual ethylmalonate subunit: a hrPKS and acyl CoA carboxylase are responsible for its formation. Bioinformatic analysis of the genomes of several fungi producing related xanthones, e.g. the widely occurring ergochromes, and related metabolites allows detailed annotation of the biosynthetic genes, and a rational overall biosynthetic scheme for the production of fungal dimeric xanthones to be proposed.

Mangostanaxanthone VIIII, a new xanthone from Garcinia mangostana pericarps, α-amylase inhibitory activity, and molecular docking studies

Abstract: A new xanthone: mangostanaxanthone VIIII [1,3,5,6,7-pentahydroxy-2-(3-methylbut-2-enyl)-8-(3-hydroxy-3-methylbut-1-enyl) xanthone] (5) and four known xanthones: mangostanaxanthones I (1) and II (2), γ-mangostin (3), and mangostanaxanthone VII (4) were separated and characterized from the acetone fraction of Garcinia mangostana L., Clusiaceae (mangosteen) pericarps. Their structures were established based on various spectroscopic analyses in addition to HRMS and comparison with the literature. The α-amylase inhibitory potential of the isolated metabolites was evaluated. Compounds 1, and 5 had the highest activity with % inhibition 72.5, 86.5, and 81.8, respectively compared to acarbose (97.1%, reference α-amylase inhibitor). The molecular docking study of the tested metabolites was estimated to shade up the rational explanation of the α-amylase inhibitory activity results. Moreover, the pharmacokinetic parameters were assessed using Swiss ADME. It is noteworthy that 1, 2, and 5 had similar binding poses as the X-ray crystal structure of acarbose, whereas the other metabolites possessed different binding mode that decreased their inhibitory capacity. Thus, these data reinforced the health benefit of mangosteen as an alternative medicine to help lowering the postprandial glucose absorption. Therefore, it could have a good potential for the treatment of diabetes.

Synthesis, Biological Evaluation, and In Silico Studies of Novel Aminated Xanthones as Potential p53-Activating Agents.

Abstract: Xanthone scaffold has been regarded as an attractive chemical tool in the search for bioactive molecules with antitumor activity, and in particular two xanthone derivatives, 12-hydroxy-2,2-dimethyl-3,4-dihydro-2H,6H-pyrano [3,2-b]xanthen-6-one (4) and 3,4-dimethoxy-9-oxo-9H-xanthene-1-carbaldehyde (5), were described as a murine double minute 2 (MDM2)-p53 inhibitor and a TAp73 activator, respectively. The xanthone 5 was used as a starting point for the construction of a library of 3,4-dioxygenated xanthones bearing chemical moieties of described MDM2-p53 inhibitors. Eleven aminated xanthones were successfully synthesized and initially screened for their ability to disrupt the MDM2-p53 interaction using a yeast cell-based assay. With this approach, xanthone 37 was identified as a putative p53-activating agent through inhibition of interaction with MDM2. Xanthone 37 inhibited the growth of human colon adenocarcinoma HCT116 cell lines in a p53-dependent manner. The growth inhibitory effect of xanthone 37 was associated with the induction of G1-phase cell cycle arrest and increased protein expression levels of p53 transcriptional targets. These results demonstrated the potential usefulness of coupling amine-containing structural motifs of known MDM2-p53 disruptors into a 3,4-dioxygenated xanthone scaffold in the design of novel and potent p53 activators with antitumor activity and favorable drug-like properties. Moreover, in silico docking studies were performed in order to predict the binding poses and residues involved in the potential MDM2-p53 interaction.

Photochemical Deracemization of Chiral Sulfoxides Catalyzed by a Hydrogen-Bonding Xanthone Sensitizer

Abstract: Several chiral sulfoxides with a lactam hydrogen-bonding site were prepared and their photochemical behavior was studied in the presence of xanthone and thioxanthone sensitizers. While acyclic sulfoxides showed only decomposition, chiral benzothiazinone-1-oxides with a stereogenic sulfur atom underwent a stereomutation upon irradiation at λ = 366 nm in the presence of catalytic quantities of a xanthone sensitizer. A chiral xanthone with a 1,5,7-trimethyl-3-azabicyclo-[3.3.1]nonan-2-one backbone was employed in catalytic quantities (5 mol%) to achieve a deracemization reaction of racemic benzothiazinone-1-oxides in acetonitrile solution. Five substrates could be successfully deracemized in good yields and with up to 55% ee.

α-Amylase inhibition of xanthones from Garcinia mangostana pericarps and their possible use for the treatment of diabetes with molecular docking studies.

Abstract: Chromatographic separation of the methanol extract of Garcinia mangostana (mangosteen, Guttiferae) dried pericarps led to the isolation and structural characterization of a new xanthone, namely garcimangostin A (5), together with garcixanthone A (1), gartanin (2), normangostin (3), and garcinone C (4). Their structural characterization was achieved using various NMR spectroscopic tools as well as HRMS. Their α-amylase inhibitory (AAI) potential was assessed. It is noteworthy that 5 had the most potent inhibitory effect with % inhibition 94.1 compared to acarbose (96.7%). Moreover, the molecular modeling studies were estimated. The observed scoring results correlated to those results of the AAI assay. Interestingly, 5 was completely fitting with acarbose structure and a superimposition of acarbose complexed structure with 5 in the enzyme binding site was observed. The AAI activity of 5 could be attributed to the xanthone moiety insertion in the active site of the enzyme via H-bonds network and pi-pi interactions. PRACTICAL APPLICATIONS: Garcinia mangostana is a widely consumed fruit for its unique pleasant aroma and sweet taste. Also, it contains valuable nutritious compounds that are advantageous for human body. It is used as various traditional medicines for treating several ailments such as skin infection, hyperkeratosis, eczema, wounds, psoriasis, amebic dysentery, cholera, diarrhea, and suppuration. The findings of this work can demonstrate the significant AAI potential of G. mangostana xanthones. Therefore, mangosteen as a functional food could help in lowering the postprandial glucose absorption and identifying lead compounds from α-amylase inhibition for the treatment and/or prevention of diabetes and obesity.

Anti-phytopathogenic sesquiterpenoid-xanthone adducts from potato endophytic fungus Bipolaris eleusines

Abstract: A bioguided separation on the cultures of the potato endophytic fungus Bipolaris eleusines led to the isolation of two anti-phytopathogenic (Alternaria solani) sesquiterpenoid-xanthone adducts, namely bipolins I and J (1 and 2). Their structures were established via extensive spectroscopic analysis. Compounds 1 and 2 exhibit potent inhibitory activity against A. solani with MIC values of 8 and 16 μg mL−1, respectively.

Synthesis of Novel Xanthone Analogues and Their Growth Inhibitory Activity Against Human Lung Cancer A549 Cells

Abstract: Purpose Xanthones demonstrated an array of pharmacological activities via non-covalent DNA interaction and have been widely utilized in new drug research. The introduction of the polar 1,2,3-triazole ring located at the C3-position of xanthone has not been reported thus far. Methods In the present study, a series of xanthone derivatives were designed, synthesized, and characterized through 1H NMR, 13C NMR, and MS. The methyl thiazolyl tetrazolium method was used to evaluate the cytotoxic activity of compounds. Furthermore, the structure-activity relationship and the potential mechanism of target compounds were investigated. Results The IC50 showed that the inhibitory activity of 18 target compounds was higher than that of the original xanthone intermediate 4. In particular, compound 1j was the most active agent against A549 cancer cells (IC50 = 32.4 ± 2.2 μM). Moreover, apoptosis analysis indicated different contributions of early/late apoptosis to cell death for compounds 1h and 1j. The results of Western blotting analysis showed that compound 1j significantly increased the expression of caspase 3, Bax, and c-Jun N-terminal kinase, and regulated p53 to a better healthy state in cancer cells. Conclusion We synthesized several derivatives of xanthone and evaluated their cytotoxicity. The evidence suggested that compound 1j possessed greater anticancer potential for further evaluations.

Discovery of a New Xanthone against Glioma: Synthesis and Development of (Pro)liposome Formulations.

Abstract: Following our previous work on the antitumor activity of acetylated flavonosides, a new acetylated xanthonoside, 3,6-bis(2,3,4,6-tetra-O-acetyl-β-glucopyranosyl)xanthone (2), was synthesized and discovered as a potent inhibitor of tumor cell growth. The synthesis involved the glycosylation of 3,6-di-hydroxyxanthone (1) with acetobromo-α-d-glucose. Glycosylation with silver carbonate decreased the amount of glucose donor needed, comparative to the biphasic glycosylation. Xanthone 2 showed a potent anti-growth activity, with GI50 < 1 μM, in human cell lines of breast, lung, and glioblastoma cancers. Current treatment for invasive brain glioma is still inadequate and new agents against glioblastoma with high brain permeability are urgently needed. To overcome these issues, xanthone 2 was encapsulated in a liposome. To increase the well-known low stability of these drug carriers, a proliposome formulation was developed using the spray drying method. Both formulations were characterized and compared regarding three months stability and in vitro anti-growth activity. While the proliposome formulation showed significantly higher stability, it was at the expense of losing its biocompatibility as a drug carrier in higher concentrations. More importantly, the new xanthone 2 was still able to inhibit the growth of glioblastoma cells after liposome formulation.

Two new xanthones and cytotoxicity from the bark of Garcinia schomburgkiana.

Abstract: Two new xanthone derivatives, named schomburgones A (1) and B (2), along with eight known compounds, including xanthones (3–8) and anthraquinones (9–10) were isolated from the bark of Garcinia schomburgkiana Their structures were determined by spectroscopic analysis especially 1D and 2D NMR spectroscopies All isolated compounds were evaluated for their cytotoxicity against five cancer cell lines (KB, HeLa S-3, HT-29, MCF-7 and HepG-2) Compounds 3–6 and 8 showed good cytotoxicity against all the five cancer cell lines with IC50 values in the range of 145–946 µM

Xanthones from the Bark of Garcinia xanthochymus and the Mechanism of Induced Apoptosis in Human Hepatocellular Carcinoma HepG2 Cells via the Mitochondrial Pathway.

Abstract: Xanthones are important chemical constituents of Garcinia xanthochymus and varied bioactivities including cytotoxicity. However, their anti-tumor mechanism has remained unknown. Here, we isolated and identified a new xanthone named garciniaxanthone I (1) and five known compounds from the bark of G. xanthochymus. Their structures were elucidated by NMR analysis and HRESIMS. The anti-proliferation activities of all isolated compounds were evaluated on four human tumor cell lines (HepG2, A549, SGC7901, MCF-7). The results demonstrated that the anti-proliferation activity of xanthone was related to the number and location of prenyl groups. We further found that garciniaxanthone I (GXI) could induce HepG2 apoptosis and enhance the expression of cleaved caspase-8, caspase-9, and caspase-3. GXI could also increase Bax level and concurrently reduce the overexpression of Bcl-2, Bcl-XL, Mcl-1, and surviving in HepG2 cells. Moreover, GXI could inhibit cell migration of HepG2 cells by inhibiting the expressions of MMP-7 and MMP-9. In summary, our study suggests that GXI could induce HepG2 apoptosis via the mitochondrial pathway and might become a lead compound for liver cancer treatment.

Xanthone Conjugated Amino Acids as Potential Anticancer and DNA Binding Agents: Molecular Docking, Cytotoxicity and SAR Studies

Abstract: Background Amino acids conjugated with heterocyclic molecules are well known for their effective bioactive properties. In search of effective anticancer agents, a series of xanthone linked amino acids 2-23 were synthesized and tested for in vitro anticancer activity. Methods In vitro anticancer activity of the synthesized xanthone linked amino acids 2-23 are tested against three different cancer cell lines MCF-7, MDA-MB-435 and A549 by MTT assay and validated by DNA binding and molecular docking approaches. Doxorubicin and ethidium bromide used as standard and positive control respectively. Results Compounds 7, 8 and 9 exhibited potent anticancer activity against tested cancer cell lines and DNA binding study using methyl green. In the molecular docking study, binding interactions of the most active compounds 7, 8 and 9 were confirmed to molecular surface of DNA. Conclusion Structure-Activity Relationship (SAR) showed that the aromatic and hydrophobic amino acids (phenylalanine, tyrosine, and tryptophan) favoured the DNA binding studies and anticancer activity whereas, aliphatic amino acids showed least anticancer activity.

The comparative toxicity of xanthones and tannins in mangosteen (Garcinia mangostana Linn.) pericarp extract against BHK-21 fibroblast cell culture

Abstract: Objective: The objective of this study is to compare the toxicity level of xanthones and tannins derived from mangosteen pericarp extract at specific concentrations against BHK-21 fibroblast cell cultures. Methods: Mangosteen was extracted using a maceration method with ethanol 96%. Xanthones were isolated from the chloroform extract, whereas tannins were isolated using acetone alcohol and serial diluted to 100% concentration. Toxicity levels were monitored after 24 h using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide assay technique by ELISA reader at 620 nm. Results: Viable cells of BHK-21 against xanthone concentration began to decrease (40.24%) at 3.98% xanthones, whereas viable cells of BHK-21 against tannin concentration began to decrease (68.06%) at 2.2% tannins. Conclusion: It is suggested that tannins were more toxic than the xanthones derived from mangosteen pericarp.

Study on Synthesis and Biological Evaluation of 3-Aryl Substituted Xanthone Derivatives as Novel and Potent Tyrosinase Inhibitors.

Abstract: Tyrosinase plays a key role in the melanin biosynthesis since it catalyzes the transformation of tyrosine into L-dopaquinone. A large number of studies have also shown that molecules to efficiently inhibit the activity of tyrosinase would be potentially used in treating many depigmentation-related disorders. In this study, we targeted a series of structure-based 3-aryl substituted xanthone derivatives in which diverse functional groups were respectively attached on 3-aromatic ring moiety as new tyrosinase inhibitors. The results demonstrated that all obtained compounds had potent tyrosinase inhibitory activities with IC50 values at micromolar range. Especially, compound 4t was found to be the most active tyrosinase inhibitor with the IC50 value of 11.3 µM, uncovering that the introduction of the proper hydroxyl group in the 3-aromatic ring was beneficial for enhancing the inhibitory potency against tyrosinase. Moreover, the inhibition mechanism and inhibition kinetics studies revealed that compound 4t presented such inhibitory effect by acting as the reversible and competitive-uncompetitive mixed-II type inhibitor. Further molecular docking simulation showed that 3-aromatic ring of compound 4t was inserted into the narrow regions of binuclear copper-binding site at the bottom of the enzyme binding pocket, while the xanthone skeleton was positioned at the surface of tyrosinase. Taken together, these data suggested that such type of molecules might be utilized for the development of new and promising candidate for the treatment of depigmentation-related disorders.

Structural Analysis of Polygalaxanthones, C-Glucosyl Xanthones of Polygala tenuifolia Roots

Abstract: Polygalaxanthone III, a xanthone glycoside that is a major constituent of "Polygala Root" (Polygala tenuifolia roots, Onji in the Japanese Pharmacopoeia), has been used as a standard in the quality control of crude drugs. However, we previously noted differences in the chromatographic properties of one of three samples of polygalaxanthone III. Therefore, standardization of the standard itself is extremely important. The structures of three standard samples commercially available as polygalaxanthone III were characterized by LC/MS and NMR. LC/MS analysis revealed that two molecular types exist. Both types are chromatographically separable but have an identical mass number with distinguishable MS/MS spectra. One dimensional (1D)-NMR analyses demonstrated that both had the same xanthone moiety and heteronuclear multiple bond correlation (HMBC) analyses revealed that they are structural isomers at the connecting position of glucose to apiose 1-position. Consequently, the isomers were identified as polygalaxanthone III and its regioisomer, polygalaxanthone XI. Based on the findings, we recommend using the LC-MS/MS detection method, which discriminates polygalaxanthone III and XI, to confirm the quality of the standard.