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Urease is an important virulence factor involved in the colonization and infection of gastric mucosa by Helicobacter pylori. In this work, the urease inhibitory activity of a series of γ-alkylidenebutenolides analogues of natural rubrolides is presented. The compounds were prepared from a commercial 3,4-dibromofuran-(5H)-2-one, as previously reported, including three new derivatives. The rubrolide analogues (at 500 µM) showed percentages of urease inhibition ranging from 20.7 to 99.3%. The most active compounds (IC50 from 111.5 to 306.0 µM) were shown to be more potent than hydroxyurea (IC50 844.4 µM), a standard urease inhibitor. Rubrolide analogues with phenolic hydroxyl groups revealed higher potency compared with other substances evaluated. Their physicochemical parameters (partition coefficient, molecular weight, hydrogen bonding acceptors, number of hydrogen bonding donor groups, number of rotatable bonds, and the number of aromatic bonds) related to general pharmacokinetic requirements showed drug-like properties for the evaluated rubrolide analogues. Docking studies suggest that the presence of hydroxy groups at the ortho position favors both the formation of reversible interactions with urease and the formation of a covalent adduct with the active site causing blocking of the enzyme, like what happens with catechol, its natural inhibitor. The high biological activity herein reported indicates that rubrolides constitute promising leads for the development of a new class of urease inhibitor drugs. [ABSTRACT FROM AUTHOR]

Background: Fungi biosynthesize a wide range of chemically diverse secondary metabolites during processes of competition with other micro- and macro-organisms, symbiosis, parasitism, or pathogenesis. Some of these natural compounds have antibiotic properties, which allow the microbe to inhibit and/or kill their microbial competitors. Results: In the course of an ongoing search for novel bioactive metabolites from Trichoderma harzianum M10 using OSMAC (One Strain MAny Compounds) strategy, a bioactive chromone derivative has been isolated. The 5-hydroxy-2,3-dimethyl-7-methoxychromone (1), purified for the first time from T. harzianum M10 and induced in specific medium (potato dextrose broth, PDB) and condition (light and shaking), has been obtained as pure crystals and its structure has been fully characterized using X-ray and spectroscopic methods. This metabolite revealed a significant antibiotic activity against Rhizoctonia solani (45% of growth inhibition after 24 h of incubation at a concentration of 100 ng plug−1) and significantly reduced the viability of colorectal human cancer cells in a concentration-dependent manner. Moreover, metabolomic analysis allowed the identification of compounds modulated by the cultivating conditions. Among the statistically different molecules detected it was possible to identify siderophores, such as ferricrocin and coprogen B, harzianic acid (and its derivatives), and butenolides. Conclusion: OSMAC strategy represents a valuable approach to overcome the limitations of experiments performed under laboratory conditions. Indeed, it is possible to modulate metabolites production by changing medium and conditions applied to the cultures. A specific set of conditions induced the production of a secondary metabolite never isolated from T. harzianum M10. The compound, a methoxychromone derivative, characterized by X-ray diffraction, mass spectrometry, IR, and NMR, displayed antimicrobial and antitumor activities. [ABSTRACT FROM AUTHOR]

The effects of Piper malacophyllum (C. Pesl) C. DC extracts and its isolated compounds were analysed in a mouse model of primary dysmenorrhoea (PD). Female Swiss mice (6–8 weeks old) on proestrus were intraperitoneally treated with estradiol benzoate for 3 days, to induce PD. Twenty-four hours later, animals were treated 24 h later with vehicle, plant extract, gibbilimbol B, 4,6-dimethoxy-5-E-phenylbutenolide, mixture of 4,6-dimethoxy-5-E-phenylbutenolide and 4,6-dimethoxy-5-Z-phenylbutenolide, or ibuprofen. One hour later, oxytocin was injected and the numbers of abdominal writhing were counted. Then, mice were euthanized and uteri were collected for morphometrical and histological analyses. The effects of P. malacophyllum in inflammation were investigated in mouse peritoneal neutrophils culture stimulated with LPS or fMLP (chemotaxis and mediator release). Finally, uterus contractile and relaxing responses were assessed. Similar to ibuprofen, P. malacophyllum extract and isolated compounds reduced abdominal writhing in mice with PD. Histology indicated a marked neutrophil and mast cell infiltrate in the uterus of PD animals which was attenuated by the extract. The compounds and the extract reduced neutrophil chemotaxis and inflammatory mediator release by these cells. Reduced TNF levels were also observed in uteri of PD mice treated with P. malacophyllum. The extract did not affect spontaneous uterine contractions nor those induced by carbachol or KCl. However, it caused relaxation of oxytocin-induced uterine contraction, an effect blunted by H1 receptor antagonist. Overall the results indicate that P. malacophyllum may represent interesting natural tools for reliving PD symptoms, reducing the triad of pain, inflammation and spasmodic uterus behaviour. [ABSTRACT FROM AUTHOR]

This work describes the luminescent properties of the new compound β-(hydroxyaryl)-butenolides recently discovered. The compounds were subjected to UV–Vis absorption and fluorescence analyzes when diluted in different solvents. Through the results, it was possible to observe that the β-hydroxyarylutenolides have two absorption bands, one at 289–291 nm and the other with higher intensity at 328–354 nm. The emission band between 385–422 nm is observed under excitation at 324–327 nm. The compounds showed solvatochromism as a function of the analyzed solvent. In water, fluorescence quenching of all compounds occurs. Therefore, studies with compound containing the methylenedioxy group attached in phenyl ring were carried at different concentrations of water in DMSO. The decrease in the fluorescence intensity of this compound is linearly proportional to the increase in the amount of water in the DMSO, with a minimum detection volume of 0.028%. Quantum yields of three compounds were evaluated in different solvents, showing that the relationship between the structure of the compound and the solvent is essential for a high value. The fluorescence quantum yield was also measured by Thermal Lens Spectroscopy (TLS) using DMSO as the solvent, confirming the high value for the analyzed samples. Despite being preliminary, the studies revealed that these compounds have luminescent properties that could be applied in the development of chemical sensors for detecting water in DMSO. [ABSTRACT FROM AUTHOR]

An in vivo study was performed to assay the effects of ivermectin on adult male Wistar rats. Twenty-five male Wistar rats aged 6 to 8 weeks and weighing 150-250 g were divided into five groups of five animals each for the purpose of this study. The groups received ivermectin; a mixture of ivermectin and vitamin A; a mixture of ivermectin and vitamin C; and a mixture of ivermectin, vitamin A, and vitamin C, respectively. One group served as the control group and was treated with double-distilled water. The treatment was carried out once a week for 3 weeks. The results of the study revealed that the animals were less affected as detected by slight changes in the body weight, stress oxidative parameters, serum levels of liver enzymes, kidney function indexes, cell blood counts, and sperm analysis upon exposure to ivermectin. Nevertheless, the use of vitamins A and C might have a promising effect against oxidant-antioxidant imbalance. Although, the administration of free ivermectin has fewer reactions on mammals, use of the drug supplemented with antioxidants such as vitamins A and C moderates its effects. [ABSTRACT FROM AUTHOR]

Al-doped ZnO nanostructures were prepared via a simple precipitation method and were characterized by several techniques including XRD, TEM, EDX, UV-Vis, and DLS. All XRD patterns show the hexagonal single-phase structure of pure and Al-doped ZnO nanopowders without impurity. The samples consist of particles with average sizes ranging from 53 to 60 nm measured by DLS technique. Next, the catalytic activity of pure and Al-doped ZnO nanopowders was investigated in terms of synthesis of 3,4,5-substituted furan-2(5H)-one derivatives using the three-component reaction of aldehydes, aromatic amines, and acetylenic esters. This procedure has advantages such as high yields, simple methodology, and easy work-up. [ABSTRACT FROM AUTHOR]

A number of furan-2-ylmethylidene-substituted lactones were synthesized by condensation of 5-alkylfuran-2(3H)-ones and 4-alkyldihydrofuran-2(3H)-ones with 5-substituted furan-2-carbaldehydes. The reactivity of furan-2(3H)-ones was higher than that of furan-2(5H)-ones due to formation of intermediate conjugated anion. The condensation of 4-alkyldihydrofuran-2(3H)-ones with furan-2-carbaldehydes required more severe conditions than the condensation with furan-2(3H)-ones. The substituent in the furan ring affects the reaction time and yield. [ABSTRACT FROM AUTHOR]

Strigolactones (SLs) are signal molecules of a butenolide nature from the apocarotenoids family that are synthesized by plant organisms. They are widely propagated in nature and control different aspects of plant development, which allows us to consider them as phytohormones. It is known that SLs production and release into the rhizosphere are enhanced under a deficit of basic elements of plant nutrition. In addition, these compounds carry out the signaling function in the course of establishing supraorganismal relationships upon parasitism and symbiosis. In this review, the role of SLs in the formation of arbuscular mycorrhiza (AM), which provides a symbiotic pathway of Pi uptake by plants and partly nitrogen-fixing legume nodules, is examined. The data on SLs impact on AM fungi (AMFs) development at presymbiotic and symbiotic stages of plant growth were generalized. The main peculiarities of SLs structure providing their efficiency as “branching factors” of AMF hyphae and basic mechanisms of the possible influence of SLs on AMFs, including stimulation of mitochondria biogenesis, were described. Analysis of these data and phenotypes of plant mutants with disturbances in SLs biosynthesis and its regulation and also SLs perception and transport leads to the conclusion that their role in AM development is predominantly revealed in induction of AMF hyphae branching at the presymbiotic plant growth stage and is associated with plant response to Pi deficit. Analysis of the role these components of common symbiotic signaling cascade play in the regulation of SLs biosynthesis in the course of AM development and nitrogen-fixing legumes nodules was carried out. An important role of SLs in nodule development likely caused by their endogenous influence on its organogenesis was demonstrated. A possibility of the presence of different pathways usable by a plant upon AM and nodule development for activation of common symbiotic transcriptional factors, NSP1 and NSP2, participating in the regulation of SLs biosynthesis is discussed. The data concerning structural specificity of SLs and the results of phylogenetic analysis of genes encoding different components of SLs biosynthesis and signaling pathways and also symbiotic signaling cascade in plants provide evidence for the possible transformation of SLs signaling function from the hormonal one manifested inside the plant into the communicative one providing the establishment of interorganismal relations. [ABSTRACT FROM AUTHOR]

Streptomyces hormones, sometimes called as autoregulators, are important signaling molecules to trigger secondary metabolism across many Streptomyces species. We recently identified a butenolide-type autoregulator (termed avenolide) as a new class of Streptomyces hormone from Streptomyces avermitilis that produces important anthelmintic agent avermectin. Avenolide triggers the production of avermectin with minimum effective concentration of nanomolar. Here, we describe the characterization of avaR1 encoding an avenolide receptor in the regulation of avermectin production and avenolide biosynthesis. The disruption of avaR1 resulted in transcriptional derepression of avenolide biosynthetic gene with an increase in avenolide production, with no change in the avermectin production profile. Moreover, the avaR1 mutant showed increased transcription of avaR1. Together with clear DNA-binding capacity of AvaR1 toward avaR1 upstream region, it suggests that AvaR1 negatively controls the expression of avaR1 through the direct binding to the promoter region of avaR1. These findings revealed that the avenolide receptor AvaR1 functions as a transcriptional repressor for avenolide biosynthesis and its own synthesis. [ABSTRACT FROM AUTHOR]

Purposes: The objective of this study was to evaluate the effect of supplementation with vitamin C on intestinal anastomosis healing in malnourished rats. Methods: Male Wistar rats were divided into three groups: (1) sham, well-nourished rats that received vehicle; (2) FR+Veh, rats that were subjected to food restriction and received vehicle; and (3) FR+VC, rats that were subjected to food restriction and received vitamin C. Four days before surgery, the animals received vitamin C (100 mg/kg/day) via gavage and underwent colon resection with anastomosis in a single plane. The survival rate of rats was monitored until day 7 after surgery. Regarding anastomosis tissues, we examined intra-abdominal adhesion index, hydroxyproline content, collagen density, inflammatory parameters, and oxidative damage to proteins and lipids. Results: Malnutrition decreases body weight and increases mortality; the survival rate was 90 % in group 1, 60 % in group 2, and 80 % in group 3. Vitamin C was able to increase hydroxyproline concentration and density of collagen and decrease the intra-abdominal adhesion index, as well as the infiltration of neutrophils and oxidative damage to proteins in malnourished rats compared to group treated with vehicle. Conclusions: Preoperative vitamin C supplementation can improve the intestinal anastomosis healing, biochemical alterations, and prolong survival in rats subjected to food restriction. [ABSTRACT FROM AUTHOR]

Some 3,4,5-substituted furan-2(5 H)-one derivatives, were obtained in good yields and from the corresponding three-component reaction of aromatic amines, aldehydes, and acetylenic esters by HY Zeolite nano-powder as an efficient catalyst. Graphical Abstract: [Figure not available: see fulltext.] [ABSTRACT FROM AUTHOR]

The natural product paracaseolide A is a tetracyclic dilactone containing six adjacent stereocentres. Its skeleton occupies a unique structural space among the >200,000 characterized secondary metabolites. Six different research groups have reported a chemical synthesis of this compound, five of which used a thermal, net Diels-Alder [4+2] cycloaddition and dehydration at 110 °C to access the target by dimerization of a simple butenolide precursor. Here, we report that this dimerization proceeds under much milder conditions and with a different stereochemical outcome than previously recognized. This can be rationalized by invoking a bis-pericyclic transition state. Furthermore, we find that spontaneous epimerization, necessary to correct the configuration at one key stereocentre, is viable and that natural paracaseolide A is racemic. Together, these facts point to the absence of enzymatic catalysis (that is, Diels-Alderase activity) in the cycloaddition and strongly suggest that a non-enzyme-mediated dimerization is the actual event by which paracaseolide A is produced in nature. [ABSTRACT FROM AUTHOR]

Moenomycins (Mm)-phosphoglycolipid compounds produced by Streptomyces ghanaensis ATCC14672-are considered a promising model for development of novel-class of antibiotics. In this regard it is important to generate Mm overproducing strains which would be a basis for economically justified production of this antibiotic. In this work a set of genes for synthesis and reception of low-molecular weight signaling molecules (LSM) in ATCC14672 were described and their significance for Mm production was studied. The ATCC14672 genome carries structural and regulatory genes for production of LSMs of avenolide and γ-butyrolactone families. Additional copies of LSM biosynthetic genes ssfg_07848 and ssfg_07725 did not alter the Mm production level. ATCC14672 LSMs are not capable of restoring the sporulation of butyrolactone-nonproducing mutant of S. griseus. Likewise, while the heterologous host S. lividans 1326 produced Mm, its mutant M707 (deficient in the butyrolactone synthase gene scbA) did not. Thus, while the natural level of LSMs production by ATCC14672 does not limit Mm synthesis, the former is essential for the synthesis of moenomycins. [ABSTRACT FROM AUTHOR]

To supplement hits from a high through put screening, a docking study on butenolides derivatives was performed as COX-II inhibitors. The fourteen ligands were docked inside the ligand-binding domain (LBD) of protein data bank PDB ID: 3HS5 utilizing Maestro version 9. Out of 14 compounds, compounds I and XII were found to embed in the hydrophobic pocket by forming hydrogen bonds with the amino acids HOH902, THR212, and THR206. Nitrogen of the pyrrolone ring of compound XII formed a strong hydrogen bond with THR206 with the distance of 2.221 Å and had showed highest glide score (−9.3) and lowest energy −95.66 kJ/mol. Glide score of Diclofenac and Celecoxib was found to be −10.33 and −11.37, respectively. Some other docked compounds also showed good glide scores comparable to standard anti-inflammatory drug Diclofenac, were III, V, VI, VII, IX, and XIV. Docking results were further validated by calculation of conformational energy, which was higher in case of Diclofenac and Celecoxib, i.e., −33.57 and −43.7 kJ/mol, respectively, in comparison to hypothetically designed compounds. The compounds that had highest glide score, lowest conformational energy are generally considered better and can be used for further drug designing and synthesize in laboratory. The most potent compound was XII having highest glide score and lowest conformational energy. [ABSTRACT FROM AUTHOR]

Four known butenolides were isolated from the ethyl acetate extracts of the culture broth of the marine-derived bacterium, Streptoverticillum luteoverticillatum, by bioassay-guided fractionation. The structures were identified on the basis of spectral data. The absolute configuration of compound ( 1) was determined by CD spectrum for the first time. Compounds 1–4 showed in vitro cytotoxicity against the murine lymphoma P388 and human leukemia K562 cell lines. This is the first report on the isolation of butenolides from the marine bacterium, Streptoverticillium luteoverticillatum, and their cytotoxic activities. [ABSTRACT FROM AUTHOR]

The organic extract of cultured Aspergillus terreus displayed scavenging activity against ABTS•+ and DPPH free radicals, and protective activity against glutamate-induced excitotoxicity in N18-RE-105 neuroblastoma-retina hybrid cells. Bioassay-guided fractionation of the active organic extract led to the isolation of total six butenolide derivatives, including one new metabolite, named butyroscavin (1), and five previously described metabolites, butyrolactones I (2), II (3), III (4), and VII (5), and aspernolide E (6). The planar structure of butyroscavin (1) was determined by the analysis of spectroscopic data including ESIMS (electrospray ionization mass spectrometry), and 1D and 2D NMR (nuclear magnetic resonance). The absolute configuration of butyroscavin (1) was assigned by comparison of the specific rotation with those of known compounds that share the same chiral carbon. All isolated compounds were active in the radical scavenging assay, whereas only butyrolactones I (2) and VII (5) exhibited protective activity against the glutamate-induced excitotoxicity with the EC50 of 130.1 and 91.9 μM, respectively. [ABSTRACT FROM AUTHOR]

Two new butenolides, seiridin and iso-seiridin, were isolated from culture filtrates of Seiridium cardinale, the pathogen of cypress canker, a destructive disease of Cupressus and related Coniferae These metabolites were characterized as 3-methyl-4-(2-hydroxyheptyl)-2(5H)-furanone and its 4-(3-hydroxyheptyl) isomer, respectively. Chlorotic, and necrotic symptoms were produced on leaves of either host or non-host test plants by absorption of 0.3 mg/ml solutions of either compound. These also showed antibacterial activity. [ABSTRACT FROM AUTHOR]