Related Xanthones Research Articles

Naturally Occurring Xanthones and Their Biological Implications.

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.

Xanthone derivatives from Cratoxylum formosum (Jack) Dyer subsp. pruniflorum (Kurz) Gogelin and their chemotaxonomic significance

The phytochemical investigation of the stems of Cratoxylum formosum (Jack) Dyer subsp. pruniflorum (Kurz) Gogelin led to the isolation of a new xanthone derivative cratoxanthone (1), together with seven known biogenetically related xanthone derivatives (2–8). The structures of these compounds were elucidated using comprehensive spectroscopic methods. All compounds were isolated from C. formosum for the first time. The chemotaxonomic significance of the isolates was also discussed.

Biosynthetic Pathways of Dimeric Natural Products Containing Bisanthraquinone and Related Xanthones.

Many dimeric natural products containing bisanthraquinone and related xanthones with diverse structures and versatile bioactivities have been isolated over the years. However, the complicated biosynthetic pathways of such natural products, which have remained elusive until recently, negatively impact their mass bioproduction and biosynthetic structural modification for drug discovery. In this concept, we summarize the recent progress in gene cluster mining and biosynthetic pathway elucidation of natural products containing bisanthraquinone and related xanthones. These pioneering works may pave the way for further biosynthetic pathway elucidation and structure modification of dimeric natural products through gene and protein engineering.

DETERMINATION OF THE CONTENT OF XANTONS AND THE ELEMENTAL COMPOSITION OF THE SUPERTHE EARTH AND EXTRACT IRIS LACTEA PALL

Iris lactea Pall (milky-white iris) belongs to the genus Iris L. of the Corridaceae family Iridaceae. In the form of an herb or an extract of Iris lactea Pall is found in some dietary supplements, it is included in the Alpizarin ointment, used as an antiviral agent. The use of antiviral drugs of plant origin is the safest method of treatment, given that about 90% of the population is affected by herpes. Data on the elemental composition of herbs and extracts of Iris lactea Pall are absent in the literature.
 The purpose of the work is to determine the content of xanthones and the elemental composition of the herb and the dry extract of Iris lactea Pall.
 The article presents the results of the determination of the main groups of active substances. The quantitative content of Cu, Fe, Ca, Co, Ti, Se, V, P, B, Na, Mg, K, Al, Ba, Sb, Ag, Sr, Sn, Mo, was determined by the method of atomic emission spectrometry with an ionically coupled plasma. Ni, Cd, Pb, As, Zn, Be, Mn, Cr, while the content of heavy metals and arsenic in the grass and extract does not exceed their maximum allowable content in medicinal herbal preparations. The following methods were determined by thin layer chromatography: Xanthone alpizarin and flavonoids rutin and quercetin. The method of high performance liquid chromatography (HPLC) revealed the presence of alpizarin and related xanthones.
 According to the developed method for the determination of xanthones by the HPLC method proposed in this article, the highest content of xanthones, in terms of alpizarin, is in the grass milky white – 1.14%, and in the dry extract – 1.79%.
 Milk-White Iris extract and herb are a promising source for the development of drugs that suppress the reproduction of the herpes simplex virus and its subtypes.

Prenylated xanthones from Metaxya rostrata suppress FoxM1 and induce active cell death by distinct mechanisms

BackgroundMetaxya rostrata C.Presl (Metaxyaceae) is a tree fern widespread in Central and South America and the dried rhizome is used in ethnic medicine against intestinal ulcers or tumors. An activity-guided isolation resulted in two structurally related xanthones: 2-deprenyl-rheediaxanthone B (XB) and 2-deprenyl-7-hydroxy-rheediaxanthone B (OH-XB). Hypothesis/PurposeThis study analyzed the cytotoxic activity and underlying cellular mechanisms of OH-XB for the first time in comparison to XB. MethodsWe exposed the colorectal cancer cell line SW480 and F331 fibroblasts to XB and OH-XB and determined cell viability by neutral red uptake and nuclear morphology by staining with Hoechst dye. Cell cycle distribution and the mechanism of cell death were analyzed by FACS and western blot. Knockdown of FoxM1 expression was performed with siRNA. ResultsOH-XB was at least as cytotoxic as XB in the induction of cell cycle arrest and active cell death. While both compounds strongly inhibited the transcription factor FoxM1, the cellular mechanisms of growth arrest and cell death induction differed widely: OH-XB induced S-phase cell cycle arrest in contrast to a G2-M-phase arrest by XB. It caused morphological modifications typical for classical apoptosis with increased caspase 7 activity and enhanced cleavage of PARP, while XB caused caspase 2 activation and mitotic catastrophe. After knockdown of FoxM1 expression no induction of caspase activity could be observed. ConclusionIn summary, our data clearly showed that XB and OH-XB are promising new lead compounds for cancer therapy with distinct cellular mechanisms. Both compounds are candidates for further pre-clinical and clinical investigations.

Tandem synthesis of 4-aminoxanthones is controlled by a water-assisted tautomerization: a general straightforward reaction.

Aminoxanthones constitute a group of therapeutically promising compounds that so far have been synthetically challenging. Here, we report the synthesis of both aminodihydroxanthones and fully aromatized aminoxanthones by an easy to perform, one-step multicomponent reaction of isocyanides, 3-carbonylchromones and dienophiles. The mechanism of the reaction involves a sequence of a [4 + 1] cycloaddition, iminolactone-aminofuran tautomerization, [4 + 2] cycloaddition, oxygen ring opening and aromatization. Remarkably, DFT quantum chemical computations revealed that the iminolactone-aminofuran tautomerization requires the assistance of a water molecule and, contrary to intuition, it is the rate-determining step. Conversely, both the [4 + 1] and the [4 + 2] cycloadditions have relatively low calculated energy barriers, regardless the substituents on the starting materials. Thus, we have stablished a straightforward and a wide-ranging synthesis of diversely substituted xanthones. This highly convergent process has also been applied to the synthesis of biologically important chromenophenantridines and secalonic acid related xanthone dimers.

Tautomers of Anthrahydroquinones: Enzymatic Reduction and Implications for Chrysophanol, Monodictyphenone, and Related Xanthone Biosyntheses

Reduction of emodin by sodium dithionite resulted in the formation of two tautomeric forms of emodin hydroquinone. Subsequent conversion by the short-chain dehydrogenase/reductase (SDR) MdpC into the corresponding 3-hydroxy-3,4-dihydroanthracen-1(2H)-one implies that deoxygenation is the first step in monodictyphenone biosynthesis. Implications for chrysophanol formation as well as reaction sequences in the related xanthone, ergochrome, and bianthraquinone biosyntheses are discussed.

Preparative isolation of closely‐related xanthones from Gentianella amarella ssp. acuta by High‐speed countercurrent chromatography

A methanolic extract from Gentianella amarella ssp. acuta was shown to contain several xanthones exhibiting acetylcholinesterase inhibitory activity. These xanthones were difficult to separate by conventional LC techniques, which prevented the isolation of pure compounds in sufficient amounts to perform in-depth biological testing. To develop a suitable preparative method for the separation of closely related xanthones. The methanolic extract was first partitioned with solvents of increasing polarity, in order to separate glycosides from xanthone aglycones. High-speed countercurrent chromatography (HSCCC) methods were then optimised for the fractionation of both polar and non-polar extracts. The use of HSCCC enabled the separation of xanthones which co-eluted by HPLC. Ten closely related xanthones--three of which were isomeric--were successfully isolated by developing suitable solvent systems. All compounds were obtained in sufficient amounts to allow further biological assays (e.g. up to 250 mg), including even minor compounds that were not detectable by analytical HPLC. The orthogonality of HSCCC with HPLC and the absence of solid-phase supports enabled the detection, separation and preparative isolation of closely related compounds which were difficult to resolve by other techniques.

Antiglioma action of xanthones from Gentiana kochiana: Mechanistic and structure–activity requirements

The present study identifies xanthones gentiakochianin and gentiacaulein as the active principles responsible for the in vitro antiglioma action of ether and methanolic extracts of the plant Gentiana kochiana. Gentiakochianin and gentiacaulein induced cell cycle arrest in G 2/ M and G 0/ G 1 phases, respectively, in both C6 rat glioma and U251 human glioma cell lines. The more efficient antiproliferative action of gentiakochianin was associated with its ability to induce microtubule stabilization in a cell-free assay. Both the xanthones reduced mitochondrial membrane potential and increased the production of reactive oxygen species in glioma cells, but only the effects of gentiakochianin were pronounced enough to cause caspase activation and subsequent apoptotic cell death. The assessment of structure–activity relationship in a series of structurally related xanthones from G. kochiana and Gentianella austriaca revealed dihydroxylation at positions 7, 8 of the xanthonic nucleus as the key structural feature responsible for the ability of gentiakochianin to induce microtubule-associated G 2/ M cell block and apoptotic cell death in glioma cells.

Pyranoxanthones from Calophyllum Inophyllum

AbstractPhytochemical investigation of the stem bark of Calophyllum inophyllum resulted in the isolation of a new dipyrenoxanthone, calophinone (1), together with four related xanthones (2–5). Identification of the isolated compounds was achieved through intensive studies of their spectral data, especially 2D NMR.

The Structure and Synthesis of Some Minor Xanthones From the Lichen Rinodina thiomela

The total synthesis of the xanthones 5,7-dichloro-8-hydroxy-2-methoxy-1,3-dimethyl-9H-xanthen-9-one(10),5,7-dichloro-2,8-dihydroxy-1,3-dimethyl-9H-xanthen-9-one(11),2-dechloro-8-O-methylthiomelin (6), 2-dechlorothiomelin (8), 4-dechloro-8-O-methylthiomelin (7), 4-dechlorothiomelin (5) and northiomelin (9) has been achieved. The compounds (5)-(7) and (10) were shown to be identical to the corresponding xanthones isolated from the lichen Rinodina thiomela, while chromatographic comparisons confirmed that the biosynthetically related xanthones (8), (9) and (11) were minor constituents of this species. This is the first reported natural occurrence of the xanthones (8) and (11).

Inhibitors of xanthine oxidase from Athyrium mesosorum.

Xanthine oxidase (XO) inhibitor was isolated from the aerial parts of Athylium mesosorum MAKINO (Aspidiaceae) and was identified as norathyriol (1, 3, 6, 7-tetrahydroxyxanthone) (1). The type of inhibition by 1 with respect to xanthine as a substrate was uncompetitive. The inhibitory activities of related xanthone derivatives towards XO were assayed.

Pulmonary Absorption Studies Utilizing In Situ Rat Lung Model: Designing Dosage Regimen for Bronchial Delivery of New Drug Entities

The absorption of 7‐methylsulfinylxanthone‐2‐carboxylic acid, 7‐(methylthio)xanthone‐2‐carboxylic acid, and their sodium salts from the respiratory tract of anesthetized rats was studied after intratracheal administration of 0.1ml of a solution or suspension containing the drug. At various times after administration, the lungs and trachea were removed and assayed radiochemically for unabsorbed drug. Sodium 7‐(methylthio)xanthone‐2‐carboxylate from solution was absorbed approximately 20 times faster than sodium 7‐methylsulfinylxanthone‐2‐carboxylate from a solution. The absorption from solutions was three to four times faster than the absorption from suspensions. For inhalation aerosol dosage forms intended for prophylactic use, the drug entity with slower systemic absorption probably would be more desirable than the drug entity with rapid absorption. Rapid systemic absorption following inhalation of powder or liquid aerosols would lead to more frequent dosing if the biological activity is related to the drug concentration in the tracheobronchial tissues. Therefore, the powder or liquid inhalation aerosols of organic acids rather than the corresponding sodium salts may be preferable for designing a dosage regimen. However, if the dosage form is intended for utilizing the bronchodilator activity of the compound, the drug entity with rapid absorption is more desirable. Therefore, in the treatment of asthmatic attacks, liquid or powder inhalation aerosols of the sodium salt of the rapidly absorbing drug entity are preferable. The absorption rates were directly proportional to concentration when the initial concentration of sodium 7‐methylsulfinylxanthone‐2‐carboxylate was varied over a 333‐fold range. The effect of the pH of the drug solution administered intratracheally to the rat lung indicated a sharp increase in the pulmonary absorption at a pH near the pKa. The results suggested that structurally related xanthones are absorbed possibly by passive diffusion across the lipoidal region of the pulmonary membranes and that the absorption of organic acids and organic electrolytes is mainly controlled by the lipid solubility of the unionized species.

Constituents of Mammea americana L. XII: Biological Data for Xanthones and Benzophenones

Sarcoma 180 inhibition data are presented for a number of related xanthones and benzophenones; a few showed significant activity. One of these was also tested in vivo against Ehrlich ascites tumor. Four hydroxyxanthones isolated from a polar extract of Mammea americana L. (Guttiferae) seeds did not account for the activity of the extract. The results of two antibacterial assays for a few of these compounds are also presented.

Biogenesis of xanthones in Gentiana lutea

Biogenetic studies indicate that gentisein and related xanthones are derived from a combination of both acetate and shikimate precursors, with the involvement of 2,3′,4,6-tetrahydroxybenzophenone in an oxidative coupling conversion into the xanthone.

Extractives from guttiferae. Part IX. The isolation of buchanaxanthone and two related xanthones from Garcinia buchananii Baker

Buchanaxanthone, 1,5,6-trihydroxyxanthone, and 1,5-dihydroxyxanthone have been isolated from the heartwood of Garcinia buchananii Baker. Buchanaxanthone is shown by u.v. and n.m.r. spectroscopy and by synthesis to be 1,6-dihydroxy-5-methoxyxanthone.

Extractives from guttiferae—VIII

Abstract The heartwood of Calophyllum scriblitifolium Henderson and Wyatt-Smith is shown to contain three new structurally related xanthones. These are 6-(4-hydroxy-3-methylbutanyl)1,5-dihydroxyxanthone, 6-(4-hydroxy-3-methylbut-2-enyl)1,5-dihydroxyxanthone and 6-(3,3-dimethylallyl)1,5-dihydroxyxanthone.