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Eugenol-ß-cyclodextrin complex has been widely used because of the enhanced stability and conservation of the properties of eugenol. Applications in food and health sciences have been shown previously, which makes this complex an excellent model to understand and develop methodologies for the analysis and prediction of physical properties. In this work, the dynamics of eugenol incorporated into ß-cyclodextrin are presented, using NMR relaxation rates, and the predictive capabilities of molecular dynamics simulations are discussed. Results show a hindered rotation of eugenol around the principal inertial axes when located inside ß-cyclodextrin. Moreover, a translational movement of the whole complex is demonstrated.

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Metabolic syndrome is a set of risk factors that consist of abdominal obesity, arterial hypertension, alterations in the lipid profile, and hyperglycemia. The current therapeutic strategy includes polypharmacy, using three or more drugs to control each syndrome component. However, this approach has drawbacks that could lead to therapeutic failure. Multitarget drugs are molecules with the ability to act on different targets simultaneously and are an attractive alternative for treating complex diseases such as metabolic syndrome. Previously, we identified a triamide derivative of 5-aminoanthranilic acid that exhibited hypoglycemic, hypolipemic, and antihypertensive activities simultaneously. In the present study, we report the synthesis and in combo evaluation of new derivatives of anthranilic acid, intending to identify the primary structural factors that improve the activity over metabolic syndrome-related parameters. We found that substitution on position 5, incorporation of 3,4-dimethoxyphenyl substituents, and having a free carboxylic acid group lead to the in vitro inhibition of HMG-CoA reductase, and simultaneously the diminution of the serum levels of glucose, triglycerides, and cholesterol in a diet-induced in vivo model.

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Encapsulation is one of the technologies applied for the formulation of biological control agents. The function of the encapsulating matrix is to protect the biological material from environmental factors, while dehydration allows for its viability to be prolonged. An advantage of dehydrated encapsulation formulations is that they can be stored for long periods. However, vegetative cells require low-stress dehydration processes to prevent their loss of viability. Herein we describe the fabrication of a dehydrated encapsulate of the Streptomyces CDBB1232 mycelium using sodium alginate with a high concentration of mannuronic acid; sodium alginate was added with YGM medium for mycelium protection purposes. The encapsulation was carried out by extrusion, and its dehydration was carried out in a rotating drum fed with air at room temperature (2-10 L min-1). The drying of the capsules under air flows higher than 4 L min-1 led to viability loss of the mycelium. The viability loss can be decreased up to 13% by covering the alginate capsules with gum arabic. Compared to conventional dehydration processes, air moisture removal can be lengthy, but it is a low-cost method with the potential to be scaled.

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Metabolic syndrome (MetS) is a complex disease that affects almost a quarter of the world's adult population. In MetS, diabetes, obesity, hyperglycemia, high cholesterol, and high blood pressure are the most common disorders. Polypharmacy is the most used strategy for managing conditions related to MetS, but it has drawbacks such as low medication adherence. Multitarget ligands have been proposed as an interesting approach to developing drugs to treat complex diseases. However, suitable preclinical models that allow their evaluation in a context closer to a clinical situation of a complex disease are needed. From molecular docking studies, compound 1b, a 5-aminoanthranilic acid derivative substituted with 4'-trifluoromethylbenzylamino and 3',4'-dimethoxybenzamide moieties, was identified as a potential multitarget drug, as it showed high in silico affinity against targets related to MetS, including PPAR-α, PPAR-γ, and HMG-CoA reductase. It was evaluated in a diet-induced MetS rat model and simultaneously lowered blood pressure, glucose, total cholesterol, and triglyceride levels after a 14-day treatment. No toxicity events were observed during an acute lethal dose evaluation test at 1500 mg/kg. Hence, the diet-induced MetS model is suitable for evaluating treatments for MetS, and compound 1b is an attractive starting point for developing multitarget drugs.

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Cartilage-forming lesions include tumours that can vary in severity from benign enchondromas to high-grade malignant chondrosarcomas. Chondrosarcoma is the second most frequent malignant bone tumour, accounting for 20-30% of all malignant bone neoplasms. Surgery is the standard treatment for cartilage tumours (CTs); however, their incidental diagnosis and the difficult differentiation of low-grade lesions like chondrosarcoma grade I from benign entities like enchondroma are challenges for clinical management. In this sense, the search for circulating biomarkers for early detection and prognosis is an ongoing interest. Targeted metabolomics is a powerful tool that can propose potential biomarkers in biological fluids as well as help to discover disturbed metabolic pathways to reveal tumour pathogenesis. In this context, the aim of this study was to investigate the 1 H nuclear magnetic resonance metabolomic serum profile of patients with CTs contrasted with healthy controls. Forty-one metabolites were identified and quantified; the multivariate statistical methods principal component analysis and partial least squares discriminant analysis reveal a clear separation of the CT group, that is, the differential metabolites that were involved in two main metabolic pathways: the taurine and hypotaurine metabolism and synthesis and degradation of ketone bodies. Our results represent preliminary work for emergent serum-based diagnostics or prognostic methods for patients with chondrogenic tumours.

Assuntos

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Infection from multidrug resistant bacteria has become a growing health concern worldwide, increasing the need for developing new antibacterial agents. Among the strategies that have been studied, biofilm inhibitors have acquired relevance as a potential source of drugs that could act as a complement for current and new antibacterial therapies. Based on the structure of 2-alkyl-3-hydroxy-4-quinolone and N-acylhomoserine lactone, molecules that act as mediators of quorum sensing and biofilm formation in Pseudomonas aeruginosa, we designed, prepared, and evaluated the biofilm inhibition properties of long chain amide derivatives of 2-amino-4-quinolone in Staphylococcus aureus and P. aeruginosa. All compounds had higher biofilm inhibition activity in P. aeruginosa than in S. aureus. Particularly, compounds with an alkyl chain of 12 carbons exhibited the highest inhibition of biofilm formation. Docking scores and molecular dynamics simulations of the complexes of the tested compounds within the active sites of proteins related to quorum sensing had good correlation with the experimental results, suggesting the diminution of biofilm formation induced by these compounds could be related to the inhibition of these proteins.

Assuntos

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In this work, microwave synthesis, chemical, optical and electrochemical characterization of three small organic molecules, TPA-TPD, TPA-PT-TPD and TPA-TT-TPD with donor-acceptor structure and their use in organic photovoltaic cells are reported. For the synthesis, 5-(2-ethylhexyl)-4H-thieno[3,4-c]pyrrole-4,6(5H)-dione was used as electron withdrawing fragment while the triphenylamine was used as electron donating fragment. Molecular electronic geometry and electronic distribution density were established by density functional theory (DFT) calculations and confirmed by optical and chemical characterization. These molecules were employed as electron-donors in the active layer for manufacturing bulk heterojunction organic solar cells, where [6,6]-phenyl C71 butyric acid methyl ester (PC71BM) was used as electron-acceptor. As cathode, Field's metal (FM), an eutectic alloy (Bi/In/Sn: 32.5%, 51%, and 16.5%, respectively) with a melting point above 62 °C, was easily deposited by drop casting under vacuum-free process and at air atmosphere. Prepared devices based on TPA-TPD:PC71BM (1:4 w/w ratio) presented a large VOC = 0.97 V, with JSC = 7.9 mA/cm², a FF = 0.34, then, a power conversion efficiency (PCE) of 2.6%.

Assuntos

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This paper reports the synthesis of a series of piperidones 1-8 by the Mannich reaction and analysis of their structures and conformations in solution by NMR and mass spectrometry. The six-membered rings in 2,4,6,8-tetraphenyl-3,7-diazabicyclo[3.3.1]nonan-9-ones, compounds 1 and 2, adopt a chair-boat conformation, while those in 2,4-diphenyl-3-azabicyclo[3.3.1]nonan-9-ones, compounds 3-8, adopt a chair-chair conformation because of stereoelectronic effects. These stereoelectronic effects were analyzed by the (1) J C-H coupling constants, which were measured in the (13)C satellites of the (1)H NMR spectra obtained with the hetero-dqf pulse sequence. In the solid state, these stereoelectronic effects were investigated by measurement of X-ray diffraction data, the molecular geometry (torsional bond angles and bond distances), and inter- and intramolecular interactions, and by natural bond orbital analysis, which was performed using density functional theory at the ωB97XD/6311++G(d,p) level. We found that one of the main factors influencing the conformational stability of 3-8 is the interaction between the lone-pair electrons of nitrogen and the antibonding sigma orbital of C(7)-Heq (nN→σ*C-H(7)eq), a type of hyperconjugative interaction.

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An NMR titration method has been used to simultaneously measure the acid dissociation constant (pKa) and the intramolecular NHO prototropic constant ΔKNHO on a set of Schiff bases. The model compounds were synthesized from benzylamine and substituted ortho-hydroxyaldehydes, appropriately substituted with electron-donating and electron-withdrawing groups to modulate the acidity of the intramolecular NHO hydrogen bond. The structure in solution was established by 1H-, 13C- and 15N-NMR spectroscopy. The physicochemical parameters of the intramolecular NHO hydrogen bond (pKa, ΔKNHO and ΔΔG°) were obtained from 1H-NMR titration data and pH measurements. The Henderson-Hasselbalch data analysis indicated that the systems are weakly acidic, and the predominant NHO equilibrium was established using Polster-Lachmann δ-diagram analysis and Perrin model data linearization.

Assuntos

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Two new eunicellin-based diterpenes, seco-briarellinone (1) and briarellin S (2), and a known seco-asbestinin (3) have been isolated from the methanolic extract of the common octocoral Briareum asbestinum collected in Bocas del Toro, Caribbean of Panama. The structures and relative stereochemistry of the compounds were defined using extensive spectroscopic analysis including 1D, 2D-nuclear magnetic resonance (NMR) and high-resolution mass spectrometry (HRMS). Compounds 1 and 2 displayed anti-inflammatory properties inhibiting nitric oxide (NO) production induced by lipopolisacharide (LPS) in macrophages with an Inhibitory concentration 50% (IC50) of 4.7 µM and 20.3 µM, respectively. This is the first report of briarellin diterpenes containing a ketone group at C-12.

Assuntos

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The conformations and relative configurations of 20 amines, classified according to the following labeling scheme, were analyzed. Series a comprised compounds derived from N-(1-phenylethyl)cyclohexanamine, b comprised derivatives of N-[1-(naphthalen-2-yl)ethyl]cyclohexanamine, c comprised derivatives of N-(diphenylmethyl)cyclohexanamine, and d comprised derivatives of N-(propan-2-yl)cyclohexanamine. The compounds were labeled as follows: 1 indicates cyclohexanamine, 2 indicates 2-methylcyclohexanamines, 3 indicates 3-methylcyclohexanamines, 4 indicates 4-methylcyclohexanamines, and 5 indicates 4-tert-butylcyclohexanamines. These compounds were prepared without the use of stereoselective induction and, therefore, all expected stereoisomers were observed. Structural assignments were established by (1)H, (13)C, and (15)N NMR.

Assuntos

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The relative acidities of the cis and trans isomers of a series of 1,5-oxazaspiro[5.5]undecane derivatives were determined by measuring DeltapK in acid-base titrations followed by (1)H NMR. Relative structural stabilities were determined by measuring substituent chemical shift and gamma-gauche effects in (13)C, (15)N, and (17)O NMR. Crystallographic characterization of a model spiro[5.5]undecane is presented to support the basicity in solid state.

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The thermodynamic products (epsilon-lactams) of the degradation of ten different spirocyclic oxaziridines were analyzed by 1H and 13C NMR spectroscopy. The preferred conformations were determined by examining the homonuclear spin-spin coupling constant and the chemical shift effects of the N-substituent and the alkyl group of the aliphatic ring on 1H and 13C NMR spectra.

Assuntos

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The configurational properties of a series of cyclohexylidene imines are discussed on the basis of their 1H, 13C and 15N NMR spectral data.

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The relative configuration of 11 1,4-diazaspiro[4.5]decanes (1a-1j and 1m), 15 1,4-oxazaspiro[4.5]decanes (2a-2o) and 10 1,4-dioxaspiro[4.5]decanes (3a-3n) substituted at the 2-, 6-, 7- or 8-position by a methyl group or using the tert-butyl group as a model for the ananchomeric structure is reported. The relative stereochemistry was analyzed by 1H, 13C, 15N and 17O NMR and all isomers present were characterized spectroscopically. Compounds with a methyl group in the six-membered ring show a chair conformation preference with the methyl group in the equatorial position. Compounds with one or two nitrogens exhibit a tautomeric equilibrium between the imine-diazolidine forms, as demonstrated by IR and 13C NMR.

Assuntos

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HPLC-UV, (1)H NMR, (13)C NMR, and (1)H-(1)H COSY analyses revealed that exogenous capsaicin was specifically converted into 5,5'-dicapsaicin by both cell suspension cultures of Capsicum annuum var. annuum (chili Jalapeño chigol) and their soluble and NaCl-extracted cell wall protein fractions under oxidative conditions. In cell suspension cultures 5,5'-dicapsaicin was found only in biomass of capsaicin-fed cultures. This compound has not been detected before either in fresh fruits or in in vitro cultures of Capsicum. The transformation of capsaicin by different protein fractions revealed that most of the enzymatic activity was located in the NaCl-extracted, or ionic cell wall bound, protein, and that it was strictly dependent on H(2)O(2). These results might in part explain some previously described features of capsaicin production by in vitro cultures of Capsicum. The implications of the results regarding the catabolism of capsaicinoids are discussed.

Assuntos