Antimicrobial and antileishmanial xanthones from the stem bark of Allanblackia gabonensis (Guttiferae)

The phytochemical study of stem bark of Allanblackia gabonensis has resulted in the isolation and characterisation of one new xanthone derivative, named allanxanthone D, together with 10 known compounds, including 6 xanthones derivatives, allanxanthone A, 1,5-dihydroxyxanthone, 1,7-dihydroxyxanthone and 1,3,6,7-tetrahydroxy-2-(3-methylbut-2-enyl)xanthone, forbexanthone, 6-deoxyisojacareubin, one polyisoprenylated benzophenone, guttiferone F, one flavanol, epicathechin, two phytosterols, beta-sitosterol and campesterol. The structures of these compounds were established on the basis of one- and two-dimensional NMR homo- and hetero-nuclear evidence. These compounds were evaluated for their activity against Leishmania amazonensis in vitro and antimicrobial activities against a range of Gram negative and Gram positive bacteria.     

Polyisoprenylated acylphloroglucinols and a polyisoprenylated tetracyclic xanthone from the bark of Calophyllum thorelii

Two new polyisoprenylated acylphloroglucinols, thoreliones A and B, and a new polyisoprenylated tetracyclic xanthone, oxy-thorelione A, together with twelve known compounds, were isolated from the bark of Calophyllum thorelii. The new structures were determined using spectroscopic methods and chemical modification. The major compound thorelione A (1) showed moderate cytotoxic activity against MCF-7, HeLa and NCI-H460 cells with IC₅₀ values of 7.4, 9.3 and 10.6 μg/mL, respectively, using the sulforhodamine B assay.     

Tetracyclic Thioxanthene Derivatives: Studies on Fluorescence and Antitumor Activity

Thioxanthones are bioisosteres of the naturally occurring xanthones. They have been described for multiple activities, including antitumor. As such, the synthesis of a library of thioxanthones was pursued, but unexpectedly, four tetracyclic thioxanthenes with a quinazoline–chromene scaffold were obtained. These compounds were studied for their human tumor cell growth inhibition activity, in the cell lines A375-C5, MCF-7 and NCI-H460. Photophysical studies were also performed. Two of the compounds displayed GI₅₀ values below 10 µM for the three tested cell lines, and structure–activity relationship studies were established. Three compounds presented similar wavelengths of absorption and emission, characteristic of dyes with a push-pull character. The structures of two compounds were elucidated by X-ray crystallography. Two tetracyclic thioxanthenes emerged as hit compounds. One of the two compounds accumulated intracellularly as a bright fluorescent dye in the green channel, as analyzed by both fluorescence microscopy and flow cytometry, making it a promising theranostic cancer drug candidate.     

Progress on PPAPs cyclization: Guttiferone A as a case study

Guttiferone A and cyclized analogs are naturally occurring polycyclic polyprenylated acyl phloroglucinols possessing antiparasitic activities. Naturally occurring xanthones possess increased activity, but are either rare or difficult to synthesize. In this paper, three optimized methodologies to access natural, hydroxylated and non-natural xanthonic skeletons from guttiferone A are described. These compounds will serve as starting materials for further SAR studies.     

Multitarget Action of Xanthones from Garcinia mangostana against α-Amylase, α-Glucosidase and Pancreatic Lipase

Digestive enzymes such α-amylase (AA), α-glucosidase (AG) and pancreatic lipase (PL), play an important role in the metabolism of carbohydrates and lipids, being attractive therapeutic targets for the treatment of type 2 diabetes and obesity. Garcinia mangostana is an interesting species because there have been identified xanthones with the potential to inhibit these enzymes. In this study, the multitarget inhibitory potential of xanthones from G. mangostana against AA, AG and PL was assessed. The methodology included the isolation and identification of bioactive xanthones, the synthesis of some derivatives and a molecular docking study. The chemical study allowed the isolation of five xanthones (1–5). Six derivatives (6–11) were synthesized from the major compound, highlighting the proposal of a new solvent-free methodology with microwave irradiation for obtaining aromatic compounds with tetrahydropyran cycle. Compounds with multitarget activity correspond to 2, 4, 5, 6 and 9, highlighting 6 with IC₅₀ values of 33.3 µM on AA, 69.2 µM on AG and 164.4 µM on PL. Enzymatic kinetics and molecular docking studies showed that the bioactive xanthones are mainly competitive inhibitors on AA, mixed inhibitors on AG and non-competitive inhibitors on PL. The molecular coupling study established that the presence of methoxy, hydroxyl and carbonyl groups are important in the activity and interaction of polyfunctional xanthones, highlighting their importance depending on the mode of inhibition.     

Leishmanicidal and cholinesterase inhibiting activities of phenolic compounds from Allanblackia monticola and Symphonia globulifera

In a preliminary antiprotozoal screening of several Clusiaceae species, the methanolic extracts of Allanblackia monticola and Symphonia globulifera showed high in vitro leishmanicidal activity. Further bioguided phytochemical investigation led to the isolation of four benzophenones: guttiferone A (1), garcinol (2), cambogin (3) and guttiferone F (4), along with three xanthones: allanxanthone A (5), xanthone V1 (6) and globulixanthone C (7) as active constituents. Compounds 1 and 6 were isolated from S. globulifera leaves, while compounds 2-5 were obtained from A. monticola fruits. Guttiferone A (1) and F (4) showed particulary strong leishmanicidal activity in vitro, with IC50 values (0.2 microM and 0.16 microM, respectively) comparable to that of the reference compound, miltefosine (0.46 microM). Although the leishmanicidal activity is promising, the cytotoxicity profile of these compounds prevent at this state further in vivo biological evaluation. In addition, all the isolated compounds were tested in vitro for their anticholinesterase properties. The four benzophenones showed potent anticholinesterase properties towards acetylcholinesterase (AChE) and butylcholinesterase (AChE). For AChE, the IC50 value (0.66 microM) of garcinol (2) was almost equal to that of the reference compound galanthamine (0.50 microM). Furthermore, guttiferone A (1) and guttiferone F (4) (IC50 = 2.77 and 3.50 microM, respectively) were more active than galanthamine (IC50 = 8.5) against BChE.     

Insilico validation and comparison of antifungal competence and druglikeness of some natural xanthones – A step towards antimycotic therapeutics

In the current work, the xanthones (from the plant source) that possess strong experimental evidences for their antifungal properties are chosen from the literatures and docking studies were employed with a fungal protein for computational validation to simplify the process of electing the top hits among a large set of naturally occurring substituted xanthones. The results indicate that computationally 86% of xanthones under study exhibits good binding affinity towards (B.E ≥ ?7 kcal/mol) the target protein (GlcN-6-P). The current docking analysis established the Garcinone D (?10.25 kcal/mol: Garcinia Mangostana), Caledol (?10.14 kcal/mol: Calophyllum Caledonicum), Jacareubin (?9.82 kcal/mol: Calophyllum Brasiliensis), γ-mangostin (?9.79 kcal/mol: Garcinia Mangostana) and 2-deprenylrheedia xanthone (?9.64 kcal/mol: Hypericum Roperanum) as good inhibitors of GlcN-6-P among a large set of natural xanthones. And also, most of xanthones have greater binding ability than the compared antifungal drugs. The effect of substituents on binding energy have also been investigated. A detailed analysis of drug likeness for 50 xanthones were also performed and found that most of the xanthone derivatives falls under the category of drug templates.     

Prenylated Xanthone Composition of Garcinia mangostana (Mangosteen) Fruit Hull

Fourteen prenylated xanthones found in mangosteen fruit, Garcinia mangostana L., have been simultaneously separated by reversed-phase high-performance liquid chromatography with water–acetonitrile gradient elution and diode-array detection. The separated xanthones were detected at 254 nm. This new method was developed to establish a chemical fingerprint of the major constituents of mangosteen. It was also used for quantitative analysis of the two major xanthones in crude extracts of mangosteen fruit hull. This chemical fingerprint of G. mangostana extract can be used for comprehensive quality-control of mangosteen extract.     

Design of a Functional Chromene-Type Kobayashi Precursor: Gram-Scale Total Synthesis of Natural Xanthones by Highly Regioselective Aryne Annulation

The 2,2-dimethyl-2H-chromene motif is widely found in many bioactive molecules, and is a privileged structure in the pharmaceutical arena. We have developed a concise and regioselective approach to chromenes and chromanes through an aryne-based synthetic strategy. A practical, gram-scale synthetic route to a chromene-type aryne precursor was explored. Subsequently, cyclization under mild conditions afforded tetracyclic xanthone skeletons with excellent regioselectivity. Our approach provides a concise strategy for the gram-scale synthesis of chromene-type xanthones such as 6-deoxyisojacareubin, cylindroxanthone D, staudtiixanthone D, brasilixanthone A and cudracuspixanthone O.     

α-Glucosidase Inhibitory and Antimicrobial Benzoylphloroglucinols from Garcinia schomburgakiana Fruits: In Vitro and In Silico Studies

α-Glucosidase plays a role in hydrolyzing complex carbohydrates into glucose, which is easily absorbed, causing postprandial hyperglycemia. Inhibition of α-glucosidase is therefore an ideal approach to preventing this condition. A novel polyprenylated benzoylphloroglucinol, which we named schomburgkianone I (1), was isolated from the fruit of Garcinia schomburgkiana, along with an already-reported compound, guttiferone K (2). The structures of the two compounds were determined using NMR and HRESIMS analysis, and comparisons were made with previous studies. Compounds 1 and 2 exhibited potent α-glucosidase inhibition (IC_50s of 21.2 and 34.8 µM, respectively), outperforming the acarbose positive control. Compound 1 produced wide zones of inhibition against Staphylococcus aureus and Enterococcus faecium (of 21 and 20 mm, respectively), compared with the 19 and 20 mm zones of compound 2, at a concentration of 50 µg/mL. The MIC value of compound 1 against S. aureus was 13.32 µM. An in silico molecular docking model suggested that both compounds are potent inhibitors of enzyme α-glucosidase and are therefore leading candidates as therapies for diabetes mellitus.     

13 C NMR spectroscopy of substituted xanthones—II: 13C NMR spectral study of polyhydroxy xanthones

The ¹³C NMR chemical shifts of eleven hydroxy-, two hydroxymethoxy xanthones, and xanthone-C-glucoside, mangiferin, are presented and analyzed. Hydroxy substituent effects depending on substituent position as well as on shielded ring carbon position have been evaluated. Hydroxy substituent increments for xanthones are proposed. Effects of hydroxylation on carbonyl carbon shift and the methylation of hydroxy group and the corresponding shift increments which are of diagnostic value have been observed and discussed.     

Thermogravimetric—differential thermal analysis and paper chromatographic studies of complex alkali-polymethaphosphates

The polymerisation reactions leading to the formation of polyphosphates of the composition (M′_xM″_1?x/2PO₃)_n where M′ = K, or Cs and M″ = Zn, Mg or Ni have been studied by thermogravimetric methods. Differential thermal analysis has been employed for the above reaction mixtures in case of potassium derivatives. TG and DTA curves confirm the formation of complex alkali polymetaphosphates of the composition as mentioned. The absence of lower phosphates and of other cyclic phosphates has been further confirmed by paper chromatographic studies of the above-mentioned complex derivatives as well as of many other alkali polymetaphosphates prepared in an analogous manner.     

Potential of Xanthones from Tropical Fruit Mangosteen as Anti-cancer Agents: Caspase-Dependent Apoptosis Induction In Vitro and in Mice

The pericarp of mangosteen (Garcinia mangostana L.) is rich in various xanthones that are known to possess unique biological activities. In this work, we characterized the anti-proliferative and cytotoxic activities of mangosteen xanthones both in vitro and in mice. In vitro analysis with a human colorectal adenocarcinoma cell line, COLO 205, showed that mangosteen xanthones not only inhibit the proliferation of target cells but also induce their death by apoptosis that involves the activation of the caspase cascade. In vivo analysis using a mouse subcutaneous tumor model with COLO 205 cells showed that, at relatively low doses, the growth of tumors was repressed upon intratumoral administration of mangosteen xanthones. When a higher dose of mangosteen xanthones was administered, the size of tumors was reduced gradually, and, in some mice, the disappearance of tumors was seen. Histopathological evaluation and biochemical analysis of tumors that received mangosteen xanthones indicate the induction of apoptosis in tumors, which resulted in the repression of their growth and the reduction of their sizes. These results demonstrate the potential of mangosteen xanthones to serve as anti-cancer agents for the chemotherapy of cancer.     

Antimicrobial and antileishmanial xanthones from the stem bark of <Emphasis Type="Italic">Allanblackia gabonensis</Emphasis>

The phytochemical study of the stem bark of Allanblackia gabonensis has resulted in the isolation and characterization of one new xanthone derivative, named allanxanthone D, together with ten known compounds, including six xanthone derivatives, allanxanthone A, 1,5-dihydroxyxanthone, 1,7-dihydroxyxanthone and 1,3,6,7-tetrahydroxy-2-(3-methylbut-2-enyl)xanthone, forbexanthone, 6-deoxyisojacareubin, one polyisoprenylated benzophenone, guttiferone F, one flavanol, epicathechin, two phytosterols, β-sitosterol, and campesterol. The structures of these compounds were established on the basis of one- and two-dimensional NMR homo- and heteronuclear evidence. These compounds were evaluated for their activity against Leishmania amazonensis in vitro and antimicrobial activities against a range of Gram-negative and Gram-positive bacteria. Published in Khimiya Prirodnykh Soedinenii, No. 5, pp. 471–475, September-October, 2008.     

Antioxidant and antimutagenic polyisoprenylated benzophenones and xanthones from Rheedia acuminata

Dichloromethane extract of the stem bark of Rheedia acuminata yielded three benzophenones with antioxidant activity, the new one named acuminophenone A (1), guttiferone K (2) and isoxanthochymol (3), along with the known xanthones formoxanthone C (4) and macluraxanthone (5). The structures were established through interpretation of their spectroscopic data, the stereochemistry of compounds (1) and (2) were resolved by experimental and computational experiments and their antioxidant activities were measured using the DPPH, ABTS and TEAC assays. The antioxidant results showed that metabolites 1, 4 and 5 had a better antioxidant activity than the reference compound quercetin. In addition, we evaluate the mutagenicity and antimutagenicity of the CH2Cl2 extract as well as of the free radical scavenger compounds 1, 4 and 5 by the AMES Salmonella/microsomal test. No mutagenicity was found in the CH2Cl2 extract using Salmonella typhimurium strains TA98, TA100, TA102, TA1537 and TA1538, with or without S9 metabolic activation. The pure compounds neither showed mutagenicity in TA 102 strain and the most important result was the strong reduction of mutagenic effect induced by hydrogen peroxide in S. typhimurium TA102, with or without S9, showed by the compounds 1 (more than 93%) and 4 (more than 88%) at 0.02 microg/plate.     

Synthetic approach to seco-tetracenomycin natural products saccharothrixone A–C

Design and development of first synthetic approach to the functionalized tetracyclic framework of structurally novel seco-tetracenomycin natural products saccharothrixones A–C has been reported. A thermal dehydro Diels-Alder reaction of an arenyne-alkyne unit has been utilized as the key synthetic step. This strategy has been extended for the generation of a small library of diversely functionalized tetracyclic systems of seco-tetracenomycins. An approach for the synthesis of poly-hydroxyl tetracyclic system has also been described. This report represents the first synthetic approach to the tetracenomycin natural products saccharothrixones A–C.     

Proteasome-inhibitory and cytotoxic constituents of Garcinia lateriflora: absolute configuration of caged xanthones

A new biflavonoid (1), a new xanthone enantiomer (2), five new caged xanthones (3-7), and several known compounds were isolated from the stem bark of Garcinia lateriflora, collected in Indonesia. The structures of the new compounds were determined by analysis of spectroscopic data, and the absolute configuration of the caged xanthones was shown for the first time at carbons 5, 7, 8, 8a, 10a, and 27, by analysis of COSY and NOESY NMR and ECD spectra. The biflavonoids exhibited proteasome-inhibitory activity, and the known compound, morelloflavone (8) was found to have the greatest potency (IC₅₀=1.3 μM). The caged xanthones were cytotoxic toward HT-29 cells, with the known compound, morellic acid (10) being the most active (ED₅₀=0.36 μM). However, when tested in an in vivo hollow fiber assay, it was inactive at the highest dose tested (20 mg/kg).     

Densities and excess molar volumes of the ternary mixture (1-butanol+n-hexane+1-chlorobutane) at 298.15 and 313.15 K. Application of the ERAS model

Densities of the liquid mixtures (n-hexane+1-chlorobutane) and (1-butanol+n-hexane+1-chlorobutane) have been measured by the vibrating tube technique at 298.15 K and 313.15 K. With these densities, excess molar volumes were calculated. An extended version of the so-called ERAS model has been used for describing V^E of the complete ternary system at 298.15 K. Qualitatively the ERAS-model gives an adequate representation of this system, being similar the shapes of both the experimental and the predicted curves.     

Electron spin resonance spectra and magnetic susceptibilities of mixed oxides,MUO3 (M; Li,Na, K,and Rb), of pentavalent uranium

In all magnetic susceptibility versus temperature curves for MUO₃ (M; Li, Na, K and Rb) a sharp spike appeared at 16–32 K. Magnetic susceptibilities are one order smaller than those of normal U(V) complexes. ESR spectra are very broad and have g-values of 2–4.     

Elaboration,structure cristalline et proprietes physiques (transport,susceptibilité magnétique et R.M.N.) du spinelle CuV2S4

Single crystals of CuV₂S₄ have been made by chemical vapor transport with chlorine as the transport agent. Characterization by an X-ray study, density measurements by the hydrostatic technique and electron microprobe analysis were performed. They showed no deviation from stoichiometry of the compound. Refinement of the structure (space group Fd3m) has been done. Transport properties, magnetic susceptibility and N.M.R. data from 1.5°K to 300°K present discontinuities below 100°K. Observed properties are discussed in view of the previously proposed band model. The relationships between magnetic susceptibility and Knight shifts are included in this paper.