Γ-pyrone Derivatives Research Articles

An unusual 2-O-glyceryl-glycosyl-γ-pyrone from Erigeron annuus (L.) with potential antifungal activity: in-vitro and in-silico study

Phytochemical characterisation of the polar fraction of Erigeron annuus extract led to the isolation of glycerylerigeroside (1), a unique γ-pyrone derivative. Structure of 1 was decided by intensive study of NMR and mass spectra as 3-O-[4'-((1,3-dihydroxypropan-2-yl)oxy)-β-D-glucopyranoside)]-4H-pyran-4-one, with uncommon glyceroxy side chain attached to 4’ position of pyromeconic acid β-D-glucopyranoside. Antimicrobial potential of 1 was tested against Staphylococcus aureus, Salmonella enterica, and Candida albicans. Compound 1 strongly inhibited growth of Candida albicans (MIC = 17.24 µM/disc), compared to fluconazole (MIC = 16.33 µM/disc). Meanwhile, it moderately inhibited the growth of Staphylococcus aureus (MIC = 71.84 µM/disc) and Salmonella enterica (MIC = 71.84 µM/disc), as compared with thiophenicol (MIC = 14.05 µM/disc) and (MIC = 14.05 µM/disc), respectively. The binding mode of 1 with the active site of sterol 14α-demethylase (CYP51) from Candida albicans (PDB ID: 5TZ1), in combination with fluconazole, was predicted by molecular docking study and supported the antifungal activity.

Phytochemistry and biological activity of Erigeron annuus (L.) Pers.

Erigeron annuus L. is a flowering herb of North America, Europe, Asia and Russia. This plant is used as folk medicine in China for the cure of indigestion, enteritis, epidemic hepatitis, haematuria and diabetes. Phytochemical studies showed the presence of 170 bioactive compounds like coumarins, flavonoids, terpenoids, polyacetylenic compounds; γ-pyrone derivatives, sterols and various caffeoylquinic acids derived from the essential oil and organic extracts from its various parts such as aerial parts, roots, leaves, stems and flowers. The pharmacological studies demonstrated various extracts and the compounds of E. annuus to exhibit anti-fungal, anti-atherosclerosis, anti-inflammatory, antidiabetic, phytotoxic, cytoprotective, antiobesity and antioxidant activities. This article covers a critical compendious on geographical distribution, botanical description, phytochemistry, ethnomedicinal uses and pharmacological activities of E. annuus. However, further in-depth studies are needed to determine the medical uses of E. annuus and its chemical constituents, pharmacological activities and clinical applications.

Lignans, Monoterpenes and γ‐Pyrone Derivatives from Patrinia scabiosifolia with Cytotoxic Activity against HCT‐116 Cells

One new dihydrobenzofuran neolignan, patrinianeolignan I, two new monoterpenes, 6,7-dehydrodissectol A and patriniaol A, and a new γ-pyrone derivative, hydroxymaltol 3-O-(6'-O-trans-caffeoyl)-β-D-glucopyranoside, along with fifteen known lignans, eight known monoterpenes, and two known γ-pyrone derivatives, were isolated from the whole plant of Patrinia scabiosifolia. Their structures were elucidated by 1D- and 2D-NMR and HR-ESI-MS analysis. The absolute configuration of patrinianeolignan I was confirmed by circular dichroism (CD) spectrum. All compounds were evaluated in vitro for their cytotoxic activity against HCT-116 cells. The results showed that compounds patriniaol A and eudesmin exhibited moderate cytotoxicity against HCT-116 cells with IC50 values of 42.23 μM and 41.92 μM, respectively.

Fusapyrone A, a γ-pyrone derived from a desert Fusarium sp.

In this work, we isolated and characterized fusapyrone A (1), a new γ-pyrone derivative, along with six previously described compounds from the rice fermentation of Fusarium sp. CPCC 401218, a fungus collected from the desert. The structure of 1 was characterized using various spectroscopic analyses, such as MS, IR, 1D, and 2D NMR. The absolute configuration of 1 was determined through the use of 13C NMR chemical shifts, electronic circular dichroism (ECD) and optical rotation (OR) calculations. Compound 1 was found to have weak antiproliferative activity for Hela cells, with an IC50 of 50.6 μM.

Compound Analysis of Jing Liqueur and nrf2 Activation by Jing Liqueur—One of the Most Popular Beverages in China

The aim of this study is to identify the minor compounds in Jing liqueur, determine the concentration of metals, amino acids, and polysaccharides, and evaluate their Nrf2 activity and cytotoxicity. Jing liqueur that contains Chinese medicine is one of the best-selling liqueurs in China, which is also marketed in the United States. Totally, we have isolated 189 minor compounds including one new molecule (7) from a concentrated Jing liqueur, with the concentrations of most isolated compounds at micromolar levels. The structures of all these compounds were determined by using MS and NMR (1D and 2D) or by comparison of their chemical and physical data with reported values in the literatures. Besides, the concentrations of iron (0.52 mg/L), zinc (0.21 mg/L), calcium (11.0 mg/L), L-proline (2.33 mg/L), L-arginine (1.73 mg/L), total amino acids (9.84 mg/L), and total polysaccharides (337.4 mg/L) were determined. Jing liqueur, the five fractions and most of the compounds isolated from Jing liqueur were screened for their activities in the Nrf2-ARE and MTT assays. At 5.2 mg/mL the crude enhanced the Nrf2 activity. At 80 μg/mL, fraction IV weakly but fraction V strongly activated Nrf2. Among the compounds screened in the Nrf2 assay, eighteen activated Nrf2 at 40 μg/mL and compounds 51 and 126 from fraction V were the most active. The crude, all the five fractions, and Nrf2 activators were not cytotoxic toward HepG2 cells. In conclusion, Jing liqueur contains different classes of compounds including flavonoids, terpenoids, alkaloids, coumarins, cinnamic acid or coumaric acid, and phenyl ethanol (or acetic acid) derivatives, benzoquinone, naphthoquinone, anthraquinones or phenanphrene derivatives, xanthones, chromone, and γ-pyrone derivatives, lignans, other aromatic compounds, and others. Jing liqueur and the eighteen compounds, which were isolated from Jing liqueur, could activate Nrf2 without any cytotoxicity.

Penichrypyrone A: A New γ-Pyrone Derivative from the Sponge-Derived Fungus Penicillium chrysogenum LS18

A new γ-pyrone derivative, penichrypyrone A (1), along with 4 known compounds, conichaetone E (2), janthinone (3), mrlactonel (4), and aspergillusene A (5), was isolated from the EtOAc extract of the sponge-derived fungus Penicillium chrysogenum LS18. Their structures were elucidated on the basis of the detailed spectroscopic analysis and comparison with the literature data. All the isolated compounds were evaluated for their antioxidant activity.

Acrepyrone A, a new γ-pyrone derivative from an endophytic fungus, Acremonium citrinum SS-g13

A new γ-pyrone derivative, acrepyrone A (1), and three known sorbicillinoids, trichodimerol (2), dihydrotrichodimerol (3) and tetrahydrotrichodimerol (4) were isolated from an endophytic fungus, Acremonium citrinum SS-g13, harboured in the roots of the Chinese medicinal plant Fructus mori. Their structures were determined by analysing MS, NMR, and ECD data. Compound 1 was evaluated for its cytotoxic effect, antibacterial activity and quorum sensing inhibitory potential.

Fusaricates H-K and fusolanones A-B from a mangrove endophytic fungus Fusarium solani HDN15-410

Seven compounds including four undescribed fusaric acid derivatives, namely fusaricates H-K, and two undescribed γ-pyrone derivatives, named fusolanones A-B, as well as a known compound fusaric acid, were isolated from a mangrove endophytic fungus Fusarium solani. Fusaricates H-K represent the first cases of fusaric acid butanediol esters and are diastereoisomers. Their structures including absolute configurations were elucidated based on NMR, MS, chemical synthesis, chiral HPLC analysis and ECD calculations. The antibacterial activity of all undescribed compounds were tested and fusolanone B showed the best activity with MIC value 6.25 μg/mL on Vibrio parahaemolyticus.

Molecular structure of a tolyl derivative of γ-pyrone

A study of the molecular structure of a new derivative of γ-pyrone, which is assumed to be of biological and pharmacological importance, has been carried out. The detailed insight into the structure of the γ-pyrone derivative was obtained by 1H NMR, 13C NMR, IR and Raman spectroscopy. Furthermore, its crystal structure was determined by single crystal X-ray diffraction method and its behavior in solutions was examined by UV/Vis and fluorescence spectroscopy. Assignment of the vibrational spectra of the studied compound is presented and correlated to some structural parameters. DFT calculations, namely geometry optimization, frequency calculations, and NBO population analysis, were performed at B3LYP/6-311G++(d,p) level of theory and the obtained data was compared to the experimental results to further elucidate the structural details. In addition, energies of the electronic transitions were estimated using DFT calculations at the same level of theory, and the calculated results showed good agreement with experimental data. It was shown that longer CC and shorter CC bonds alternate in the pyrone ring and that the structure of the studied γ-pyrone derivative comprises two intramolecular CH⋯O bonds. All the results pointed to relatively weak π-electron delocalization inside the pyrone moiety and significantly stronger π-electron delocalization through tolyl substituents.

Chemical constituents from the aerial parts of Psammosilene tunicoides

Investigation of the 80% ethanol extract of the aerial parts of Psammosilene tunicoide afforded two carboline alkaloids (1–2), a γ-pyrone derivative (3), two p-hydroxy cinamic acid derivatives (4–5), two glycosides (6–7) and six known compounds (8–13). Their structures were established on the basis of spectroscopic analysis (1D-, 2D-NMR, ESI-MS, and HR-ESI-MS). All these compounds were evaluated for cytotoxicity against SMML-7721, A549, HCT116, and MCF-7 cell lines, and for inhibitory activity against NO production in LPS-induced RAW264.7 macrophages. However, only compound 2 had weak cytotoxic activity against the HCT116 cell line at 20μM, while the others are inactive against four human tumor cell lines and only show weak inhibition activity against NO production at 50μM.

A field effect transistor biosensor with a γ-pyrone derivative engineered lipid-sensing layer for ultrasensitive Fe3+ ion detection with low pH interference

Field effect transistors have risen as one of the most promising techniques in the development of biomedical diagnosis and monitoring. In such devices, the sensitivity and specificity of the sensor rely on the properties of the active sensing layer (gate dielectric and probe layer). We propose here a new type of transistor developed for the detection of Fe3+ ions in which this sensing layer is made of a monolayer of lipids, engineered in such a way that it is not sensitive to pH in the acidic range, therefore making the device perfectly suitable for biomedical diagnosis. Probes are γ-pyrone derivatives that have been grafted to the lipid headgroups. Affinity constants derived for the chelator/Fe3+ complexation as well as for other ions demonstrate very high sensitivity and specificity towards ferric ions with values as high as 5.1010M and a detected concentration as low as 50fM.

DFT calculations and electronic absorption spectra of some, α- and γ-pyrone derivatives

The electronic absorption spectra of 6-ethyl-4-hydroxy-2,5-dioxo-pyrano[3,2-c] quinoline 1, 6-ethyl-4-hydroxy-3-nitro-2,5-dioxo-pyrano[3,2-c] quinoline 2, 6-ethyl-4-chloro-2,5-dioxo-pyrano[3,2-c] quinoline 3, 6-ethyl-3-nitro-4-chloro-2,5-dioxo-pyrano[3,2-c] quinoline 4, 6-ethyl-4,5-dioxopyrano[3,2-c] quinoline 5, and 6-ethyl-3-nitro-6H-pyrano [3,2-c]quinoline-4,5-dione 6, were measured in polar (methanol) as well as nonpolar (dioxane) solvents. The geometries were optimized using B3LYB/6-311G (p,d) method. The most stable geometry of the studied compounds, 1–6, is the planar structure as indicates by the values of the dihedral angles. The insertion of a nitro group in position 3 in both α- and γ-pyrone ring decreases the energy gap and hence increases the reactivity of 3 and 6 compounds. Assignment of the observed bands as localized, delocalized and/or of charge transfer (CT) has been facilitated by TD-DFT calculations. The correspondences between the calculated and experimental transition energies are satisfactory. The solvent and substituent effects have been investigated. Chloro-substituent has a higher band position and intensity effects on the spectra more than hydroxyl or nitro groups.

When theory and experiment hold hands: The thermochemistry of γ-pyrone derivatives

In this work, we have determined the experimental standard ( p ∘ = 0.1 MPa ) molar enthalpies of formation, in the gas phase, of 2,6-dimethyl-4-pyrone −(261.5 ± 2.6) kJ · mol −1 and 2-ethyl-3-hydroxy-4-pyrone −(420.9 ± 2.8) kJ · mol −1. These values were obtained by combining the standard molar enthalpy of formation in the condensed phase, derived from combustion experiments in oxygen, at T = 298.15 K, in a static bomb calorimeter, with the standard molar enthalpy of sublimation, at T = 298.15 K, obtained by Calvet microcalorimetry. Additionally, high-level density functional theory calculations using the B3LYP hybrid exchange-correlation energy functional with extended basis sets have been performed for these two compounds. Good agreement was obtained between the experimental and computational results. Using the same methodology, we calculated the standard molar enthalpy of formation of gaseous 2-methyl-3-hydroxy-4-pyrone.

Phytochemical investigation of Hypericum xylosteifolium (Hypericaceae), a Caucasus endemic species

Phytochemical investigation of Hypericum xylosteifolium (Hypericaceae), a Caucasus endemic species

Lepidepyrone, a New γ-Pyrone Derivative, from Neolentinus lepideus, Inhibits Hyaluronidase

In the course of screening for hyaluronidase (HAase) inhibitory agents, a new gamma-pyrone derivative, lepidepyrone, C(8)H(10)O(5), was isolated from the cultured mycelium of the mushroom Neolentinus lepideus TMC-1102 as a major HAase inhibitory compound (IC(50) 3.3 mM). The structure of lepidepyrone was established on the basis of spectroscopic investigation.

Quantum-chemical study of the equilibrium geometry and electronic structure of certain γ-pyrone derivatives

Full ab initio optimization of molecular geometry has been carried out for certain γ-pyrone derivatives: comenic, meconic, chelidonic, and kojic acids and 5-methoxy-γ-pyrone-2-carboxylic acid in the forms of free acids, their anions, sodium and calcium salts, chelate complexes with Ca2+, and sodium and calcium salts of the chelate complexes. The calculations were carried out by the restricted Hartree-Fock method with the 6-31G* basis using the GAMESS program. The effect of salt and complex formation on the geometric and electronic structure of the molecules under consideration has been examined. To study the effect of solvation, full geometry optimization of comenic acid and its derivatives in media with the dielectric constants ɛ 10 and 78.3 has been was carried out in terms of the polarizable continuum model. The energy effects of salt and complex formation has been estimated. A possible mechanism of binding of the molecules under consideration with opioid receptors has been proposed on the basis of the calculation results.

Isolation and Structure Elucidation of Neofusapyrone from a Marine-derived Fusarium species, and Structural Revision of Fusapyrone and Deoxyfusapyrone

Three polyketides containing a pyrone ring, neofusapyrone, fusapyrone, and deoxyfusapyrone, were isolated from the marine-derived fungus Fusarium sp. FH-146. Their structures were determined by extensive ID- and 2D-NMR and MS spectral analyses. Fusapyrone and deoxyfusapyrone were originally reported as a-pyrone derivatives; however, the revised structures indicate that they are gamma-pyrone derivatives. These three compounds exhibited antimicrobial activities.

Gamma-pyrone derivatives, kojic acid methyl ethers from a marine-derived fungus Alternaria [correction of Altenaria] sp.

Kojic acid dimethyl ether (1), and the known kojic acid monomethyl ether (2), kojic acid (3) and phomaligol A (4) have been isolated from the organic extract of the broth of the marine-derived fungus Alternaria sp. collected from the surface of the marine green alga Ulva pertusa. The structures were assigned on the basis of comprehensive spectroscopic analyses. Each isolate was tested for its tyrosinase inhibitory activity. Kojic acid (3) was found to have significant tyrosinase inhibitory activity, but compounds 1, 2, and 4 were found to be inactive.

A new dual inhibitor of arachidonate metabolism isolated from Helichrysum italicum

Six acetophenones ( 1– 6) and one γ-pyrone ( 7), previously isolated from Helichrysum italicum, were tested for their ability to inhibit enzymatic and non-enzymatic lipid peroxidation, the stable 1,1-diphenyl-2-pycryl-hydrazyl free radical, superoxide scavenging and arachidonic acid metabolism. In addition, they were studied in different experimental models such as the chronic inflammation induced by 12- O-tetradecanoylphorbol 13-acetate (TPA), the phospholipase A 2-induced mouse paw oedema test, the carrageenan-induced mouse paw oedema test, and the writhing induced by acetic acid in the mouse. Of the assayed compounds, only 1 inhibited enzymatic lipid peroxidation but had no effect on non-enzymatic lipid peroxidation. None of them scavenged the superoxide radical. Study of the inhibition of arachidonic acid metabolism demonstrated that 1 was an inhibitor of both cyclooxygenase and 5-lipoxygenase, whereas 2 was a selective inhibitor of 5-lipoxygenase. In the assay of phospholipase A 2-induced mouse paw oedema, the γ-pyrone derivative inhibited oedema formation, showing a similar profile to that obtained with cyproheptadine. The acetophenones were effective at 30 and 60 min. In the carrageenan test, acetophenone 1 gave the best results and had analgesic effects in the acetic acid writhing test. In conclusion acetophenone 1 (4-hydroxy-3-(3-methyl-2-butenyl)acetophenone) is a new dual inhibitor of arachidonate metabolism, and could be a useful tool for obtaining anti-inflammatory and analgesic drugs.

Microsphaerones A and B, two novel gamma-pyrone derivatives from the sponge-derived fungus Microsphaeropsis sp.

Two new metabolites, microsphaerones A (1) and B (2), were identified from the EtOAc extract of the culture of an undescribed fungus of the genus Microsphaeropsis, isolated from the Mediterranean sponge Aplysina aerophoba. Compounds 1 and 2 represent the first examples of gamma-pyrone derivatives of the fungal genus Microsphaeropsis. The structures of the compounds were elucidated on the basis of comprehensive spectral analysis ((1)H, (13)C, (1)H-(1)H COSY, HMQC, and HMBC NMR, as well as low- and high-resolution ESI and EIMS experiments). The (S)-2-methylsuccinic acid moiety present in 1 was established by GC-MS analysis of a hydrolysis product.