Showing papers on "Xanthone published in 2021"

From Natural Products to New Synthetic Small Molecules: A Journey through the World of Xanthones.

Abstract: This work reviews the contributions of the corresponding author (M.M.M.P.) and her research group to Medicinal Chemistry concerning the isolation from plant and marine sources of xanthone derivatives as well as their synthesis, biological/pharmacological activities, formulation and analytical applications. Although her group activity has been spread over several chemical families with relevance in Medicinal Chemistry, the main focus of the investigation and research has been in the xanthone family. Xanthone derivatives have a variety of activities with great potential for therapeutic applications due to their versatile framework. The group has contributed with several libraries of xanthones derivatives, with a variety of activities such as antitumor, anticoagulant, antiplatelet, anti-inflammatory, antimalarial, antimicrobial, hepatoprotective, antioxidant, and multidrug resistance reversal effects. Besides therapeutic applications, our group has also developed xanthone derivatives with analytical applications as chiral selectors for liquid chromatography and for maritime application as antifouling agents for marine paints. Chemically, it has been challenging to afford green chemistry methods and achieve enantiomeric purity of chiral derivatives. In this review, the structures of the most significant compounds will be presented.

An Update on the Anticancer Activity of Xanthone Derivatives: A Review.

Abstract: The annual number of cancer deaths continues increasing every day; thus, it is urgent to search for and find active, selective, and efficient anticancer drugs as soon as possible. Among the available anticancer drugs, almost all of them contain heterocyclic moiety in their chemical structure. Xanthone is a heterocyclic compound with a dibenzo-γ-pyrone framework and well-known to have “privileged structures” for anticancer activities against several cancer cell lines. The wide anticancer activity of xanthones is produced by caspase activation, RNA binding, DNA cross-linking, as well as P-gp, kinase, aromatase, and topoisomerase inhibition. This anticancer activity depends on the type, number, and position of the attached functional groups in the xanthone skeleton. This review discusses the recent advances in the anticancer activity of xanthone derivatives, both from natural products isolation and synthesis methods, as the anticancer agent through in vitro, in vivo, and clinical assays.

Xanthone Glucosides: Isolation, Bioactivity and Synthesis.

Abstract: Xanthones are secondary metabolites found in plants, fungi, lichens, and bacteria from a variety of families and genera, with the majority found in the Gentianaceae, Polygalaceae, and Clusiaceae. They have a diverse range of bioactivities, including anti-oxidant, anti-bacterial, anti-malarial, anti-tuberculosis, and cytotoxic properties. Xanthone glucosides are a significant branch of xanthones. After glycosylation, xanthones may have improved characteristics (such as solubility and pharmacological activity). Currently, no critical review of xanthone glucosides has been published. A literature survey including reports of naturally occurring xanthone glucosides is included in this review. The isolation, structure, bioactivity, and synthesis of these compounds were all explored in depth.

The diverse bioactivity of α-mangostin and its therapeutic implications.

Abstract: α-Mangostin is a xanthone natural product isolated as a secondary metabolite from the mangosteen tree. It has attracted a great deal of attention due to its wide-ranging effects on certain biologic...

Visible-light promoted oxidative cyclization of cinnamic acid derivatives using xanthone as the photocatalyst.

Abstract: We have developed an efficient photocatalytic synthesis of coumarin derivatives via a tandem double bond isomerization/oxidative cyclization of cinnamic acids. Inexpensive and stable xanthone was used as the photocatalyst, and readily available Selectfluor was used as the oxidant. This method tolerates a wide range of functional groups and offers excellent chemical yields in general. Besides, the photocatalytic oxidative cyclization of cinnamic acid esters gives dimerized lignan-type products.

New protein tyrosine phosphatase inhibitors from fungus Aspergillus gorakhpurensis F07ZB1707

Abstract: Twelve new compounds, aspergorakhins A–L (1–12) coupled with one known xanthone leptosphaerin D (13), were isolated from the extract of soil-derived fungus Aspergillus gorakhpurensis F07ZB1707. Their structures were elucidated by spectroscopic data analysis including UV, IR, NMR, and HRESIMS. The absolute configurations of 5 and 8–11 were identified using ECD and OR calculations. All compounds were tested by enzyme inhibitory activity assay in vitro. Aspergorakhin A (1) showed selective activities against PTP1B and SHP1 over TCPTP with IC50 values 0.57, 1.19, and 22.97 μM, respectively. Compounds 1 and 2 exhibited modest cytotoxicity against tumor cell lines A549, HeLa, Bel-7402, and SMMC-7721 with IC50 values in the range of 6.75–83.4 μM.

Cytotoxic and α-Glucosidase Inhibitory Xanthones from Garcinia mckeaniana Leaves and Molecular Docking Study

Abstract: A new racemic xanthone, garmckeanin A (1), and eight known analogs 2-9 were isolated from the ethyl acetate (AcOEt) extract of the Vietnamese Garcinia mckeaniana leaves. Their structures were determined by MS and NMR spectral analyses and compared with the literature. The AcOEt extract showed good cytotoxicity against cancer cell lines KB, Lu, Hep-G2 and MCF7, with IC50 values of 5.40-8.76 μg/mL, and it also possessed α-glucosidase inhibitory activity, with an IC50 value of 9.17 μg/mL. Garmckeanin A (1) exhibited inhibition of all cancer cell lines, with an IC50 value of 7.3-0.9 μM. Allanxanthone C (5) successfully controlled KB growth, with an IC50 value of 0.54 μM, higher than that of the positive control, ellipticine (IC50 1.22 μM). Norathyriol (8) was a promising α-glucosidase inhibitor, with an IC50 value of 0.07 μM, much higher than that of the positive control, acarbose (IC50 161.0 μM). The interactions of the potential α-glucosidase inhibitors with the C- and N-terminal domains of human intestinal α-glucosidase were also investigated by molecular docking study. The results indicated that bannaxanthone D (2), garcinone E (4), bannaxanthone E (6), and norathyriol (8) exhibit higher binding affinity to the C-terminal than to the N-terminal domain through essential residues in the active sites. In particular, compound 8 could be assumed to be the most potent mixed inhibitor.

Synthetic approaches to biologically active xanthones: an update

Abstract: Many xanthone structures show promising biological activities. Accordingly, a breadth of synthetic strategies toward xanthone derivatives have been developed. This review surveys these methods published from 2013 to 2019, and in an integrated manner details the biological activities of key xanthone structures. The review highlights the synthesis of xanthones via the classical and the modified Grover, Shah, and Shah reaction; the use of ytterbium, palladium, ruthenium, copper catalysis; the use of chromen-4-ones as building blocks; the use of the Friedel–Crafts reaction; Ullmann-ether coupling; metal-free oxidative coupling; intermolecular and intramolecular couplings; xanthone synthesis via the intermolecular Diels–Alder reaction; a novel decarboxylative aminocatalytic strategy; use of the Michael reaction, and the use of the Knoevenagel–Michael, Michael/Michael, Michael/Henry cycloadditions; and [4+2] cycloaddition.

Identification and characterization of xanthone biosynthetic genes contributing to the vivid red coloration of red-flowered gentian

Abstract: Cultivated Japanese gentians traditionally produce vivid blue flowers because of the accumulation of delphinidin-based polyacylated anthocyanins. However, recent breeding programs developed several red-flowered cultivars, but the underlying mechanism for this red coloration was unknown. Thus, we characterized the pigments responsible for the red coloration in these cultivars. An HPLC-PDA analysis revealed the presence of phenolic compounds, including flavones and xanthones, as well as the accumulation of colored cyanidin-based anthocyanins. The chemical structures of two xanthone compounds contributing to the coloration of red-flowered gentian petals were determined by mass spectrometry and nuclear magnetic resonance spectroscopy. The compounds were identified as norathyriol 6-O-glucoside (i.e., tripteroside designated as Xt1) and a previously unreported norathyriol-6-O-(6'-O-malonyl)-glucoside (designated Xt2). The copigmentation effects of these compounds on cyanidin 3-O-glucoside were detected in vitro. Additionally, an RNA-seq analysis was performed to identify the cDNAs encoding the enzymes involved in the biosynthesis of these xanthones. Recombinant proteins encoded by the candidate genes were produced in a wheat germ cell-free protein expression system and assayed. We determined that a UDP-glucose-dependent glucosyltransferase (StrGT9) catalyzes the transfer of a glucose moiety to norathyriol, a xanthone aglycone, to produce Xt1, which is converted to Xt2 by a malonyltransferase (StrAT2). An analysis of the progeny lines suggested that the accumulation of Xt2 contributes to the vivid red coloration of gentian flowers. Our data indicate that StrGT9 and StrAT2 help mediate xanthone biosynthesis and contribute to the coloration of red-flowered gentians via copigmentation effects.

New Xanthones with Antiagricultural Fungal Pathogen Activities from the Endophytic Fungus Diaporthe goulteri L17.

Abstract: Six new xanthone dimers, diaporxanthones A-F (1-6), and an unusual xanthone monomer diaporxanthone G (7), in addition to seven known analogues (8-14), were isolated and identified from endophytic Diaporthe goulteri L17 harbored in the fruits of the salt-tolerant plant Vitex trifolia. The chemical structures of these metabolites were elucidated on the basis of nuclear magnetic resonance, high-resolution electrospray ionization mass spectrometry, and reported data in the literature. Their absolute configurations were established by single-crystal X-ray diffraction analysis together with time-dependent density functional theory electronic circular dichroism calculations. Among these compounds, compounds 1 and 6 exhibited moderate antifungal activities against Nectria sp. and Colletotrichum musae and compound 4 showed significant cytotoxicity against all selected five cancer cell lines.

A review on xanthone derivatives with antiinflammatory effects and their structure–activity relationship

Abstract: Inflammation is a response to the immune system to protect our body from the infection of foreign organisms, such as bacteria and viruses However, uncontrolled acute inflammation may lead to a variety of chronic inflammations, which may cause life-threatening hypersensitivity reactions and progressive organ damage, such as cancer, heart, and neurodegenerative diseases Nonsteroidal antiinflammatory drugs (NSAIDs) are effective but possess adverse effects at therapeutic doses, including stomach ulcers, heart attack, and stroke Thus, there is an urgent need to look for alternative antiinflammatory drugs Xanthone, a secondary metabolite from natural products, is a potential lead compound for antiinflammatory drugs The basic skeleton of xanthone is made up of two aromatic rings that fused through a carbonyl group and an oxygen atom The biological activities of xanthones are associated with their tricyclic scaffold and varied depending on the nature and/or position of their substituent groups This compound is well-known for a wide range of biological activities, including anticancer, antibacterial, antioxidant, and antiinflammatory This chapter is focused on the antiinflammatory activity of xanthones derivatives obtained from both natural resources and chemical synthesis Various types of bioassay that are commonly used to examine the antiinflammatory activity of xanthones, together with their structure–activity relationship are summarized The hydroxyl and prenyl substituent groups have contributed the most to the antiinflammatory activity of xanthones

Novel Xanthone Derivatives Impair Growth and Invasiveness of Colon Cancer Cells In Vitro

Abstract: Natural xanthones are a large group of compounds from which promising anticancer properties could be further developed by chemical modifications. This study aimed to investigate the influence of four novel xanthone derivatives based on a naturally occurring xanthone skeleton on the invasiveness of colon cancer cells in vitro. First, the concentrations required to inhibit growth of three colorectal cancer cell lines to 50% (GI50) of all the studied compounds, as well as the natural xanthones used as a reference (gambogic acid and α-mangostin), have been established (MTS reduction test). Next, the assays determining several aspects of the GI25 xanthones influence on colorectal cancer cells, including cytotoxicity, migration and invasion potential, interaction with extracellular matrix and endothelial cells, as well as expression of selected invasiveness related genes have been performed. Our results demonstrate that these novel xanthone derivatives impair colorectal cancer proliferation, motility, adhesion to extracellular matrix and to endothelial cells, and also induce apoptosis and cell death. Moreover, their activity is comparable to cisplatin and 5-fluorouracil, used as reference compounds. Conducted research indicates our compounds for further research and development as novel drugs in colorectal cancer treatment.

Antioxidant Activity of a New Xanthone Derivative from Aspidistra Letreae: In Vitro and In Silico Studies.

Abstract: A new xanthone derivative, aspidxanthone A (1), and three known compounds ((2S)-1-(β-D-galactopyranosyloxy)-3-(hexadecanoyloxy)propan-2-yl (9Z,12Z)-octadeca-9,12-dienoate (2), (25S)-spirostane-1β,3α,5β-triol (3), and asparenyldiol (4)) were isolated from the whole of the endemic species Aspidistra letreae in Vietnam. Their structures were elucidated by means of extensive spectroscopic analyses and comparison with published data. In this study, we report the isolation and structure elucidation of a new compound aspidxanthone A, antioxidant activities of the extract and isolates 1-4, and in silico molecular docking of aspidxanthone A. The ethyl acetate extract had good antioxidant activity with an IC50 value of 26.3 μg mL-1 . Among the isolates, aspidxanthone A exhibited DPPH reduction activity with an IC50 value of 11.2 μM, which is in the same range as that of the positive control, ascorbic acid. The mechanism of action of aspidxanthone A on the tyrosinase and xanthine oxidase proteins have been clarified by in silico studies.

New Compounds from Siberian Gentiana Species. II. Xanthone and C,O-Glycosylflavone

Abstract: New phenolic compounds were isolated by chromatographic separation of MeOH extracts from leaves of two Gentiana species growing in eastern Siberia. Their structures were elucidated by UV and NMR spectroscopy and mass spectrometry. The new xanthone isomangiferin-7-O-β-D-glucopyranoside (neoisomangiferin) was isolated from G. dahurica Fisch.. A new C,O-glycosylflavone, apigenin-6-C-[2″-O-(6″″-O-caffeyl)-β-D-glucopyranosyl]-β-D-glucopyranoside-4′-O-β-D-glucopyranoside (gentiflavone A) was observed in G. macrophylla Pall.

A new xanthone dimer and cytotoxicity from the stem bark of Calophyllum canum.

Abstract: A phytochemical investigation of the stem bark of Calophyllum canum resulted in the isolation of a new xanthone dimer identified as biscaloxanthone (1), together with four compounds; trapezifoliaxanthone (2), trapezifolixanthone A (3), taraxerone (4) and taraxerol (5). The structures of these compounds were determined via spectroscopic methods of IR, UV, MS and NMR (1D and 2D). The cytotoxicity of compounds 1–3 were screened against A549, MCF-7, C33A and 3T3L1 cell lines, wherein weak cytotoxic activities were observed (IC50 > 50 μM).

Molecular docking studies of α-mangostin, γ-mangostin, and xanthone on peroxisome proliferator-activated receptor gamma diphenyl peptidase-4 enzyme, and aldose reductase enzyme as an antidiabetic drug candidate.

Abstract: α-mangostin, γ-mangostin, and xanthone are some of the marker compounds found in mangosteen (Garcinia mangostana Linn.) whose activity on several treatment targets including toward the peroxisome proliferator-activated receptor gamma (PPAR-γ) receptors, diphenyl peptidase 4 (DPP-4) enzyme, and aldose reductase enzyme is unknown. Although this plant has been predicted to be used as an alternative antidiabetic treatment, it has been proven through several previous studies. This research study used three natural ligands (α-mangostin, γ-mangostin, and xanthone) whose training set was designed using Molecular Operating Environment and then compared them with several drugs on the market that are used in the treatment of diabetes mellitus. The docking molecular results showed that the α-mangostin and γ-mangostin compounds had activity toward PPAR-γ receptor, DPP-4 enzyme, and aldose reductase enzyme by showing almost similar affinity values when compared to the comparison ligands. Meanwhile, xanthone showed unfavorable results. This approach shows that α-mangostin and γ-mangostin are predicted to play a role as antidiabetic mellitus in mangosteen when viewed from these mechanisms.

New Acridone- and (Thio)Xanthone-Derived 1,1-Donor–Acceptor-Substituted Alkenes: pH-Dependent Fluorescence and Unusual Photooxygenation Properties

Abstract: A synthetic route to new heterocyclic 1,1-donor–acceptor-substituted alkenes starting with N-methyl-acridone, xanthone, and thioxanthone was investigated, leading to the acridone- and xanthone-derived products methyl 2-methoxy-2-(10-methylacridin-9 (10H)-ylidene)acetate (7) and methyl 2-methoxy-2-(9H-xanthen-9-ylidene)acetate (10) in low yields with the de-methoxylated product methyl 2-(10-methylacridin-9 (10H)-ylidene)acetate (8) and the reduced compound methyl 2-methoxy-2-(9H-xanthen-9-yl)acetate (11) as the major products from N-methyl acridone and xanthone. From thioxanthone, only the rearrangement and reduction products (14) and (15) resulted. The photophysical properties of compounds (7), (8), and (10) were investigated in the presence and absence of the Bronsted acid TFA by NMR, UV–VIS absorption, and fluorescence spectroscopy. Protonation of the acridone-derived alkenes (7) and (8) led to strong bathochromic and hyperchromic fluorescence shifts and a substantial increase in Stokes shift. The photooxygenation experiments with these substrates showed an unusual reactivity pattern in the singlet oxygen processes: whereas the electron-rich enolether (7) was chemically unreactive, (8) and (10) were oxidatively cleaved, presumably via intermediate 1,2-dioxetanes.