A previous study for the identification of acetylcholinesterase (AChE) inhibitors demonstrated that the hybrid between tyrosol, the 1,2,3-triazole nucleus, and the coumarin group, namely 7-({1-[2-(4-hydroxyphenyl)ethyl]-1H-1,2,3-triazol-4-yl}methoxy)-4-methyl-2H-chromen-2-one (10), has a high enzyme inhibitory activity. Here, we synthesized analogues of 10 via triazole with pharmacophoric groups represented by tyrosine, phenylalanine, tryptophan, and glycine in addition to evaluating the impact of coumarin-linked amino acids on AChE inhibition. We obtained eight triazoles, six of which are undescribed. In general, the presence of carboxylic acid decreased the inhibitory activity, while aromatic amino acids increased enzymatic inhibition compared to glycine. The derivative containing tyrosine, structurally most similar to 10, presented the lowest inhibition percentage, indicating that phenolic hydroxyl is not the preponderant factor for inhibition. Molecular docking was not enough to explain in vitro experiments. On the other hand, MlogP (logP calculated by the Moriguchi method) was related positively to enzymatic inhibition. To increase the hydrophobicity of the molecules, we tested the esterified triazole derivatives comparatively with the enzyme. The compound ethyl 2-(4-(((4-methyl-2-oxo-2H-chromen-7-yl)oxy)methyl)-1H-1,2,3-triazol-1-yl)acetate (6) presented an increment of inhibitory activity of 46.97 ± 1.75% at 100 μmol L-1. We also associated the best activity with the lowest van der Waals volume and molar mass values.

Benzophenones display several biological activities, including antioxidant, anticancer, and photoprotective. Furthermore, antioxidants can minimize both ultraviolet absorption and tumor development. In the present investigation, a series of twenty-six 1,2,3-triazole-benzophenone derivatives were synthesized and had their antioxidant, anticancer, and photoprotective effects evaluated. For the compounds synthesis, 4,4’-dihydroxybenzophenone (1a) and 2,4-dihydroxybenzophenone (1b) were propargylated, affording the alkynes bis(4-(prop-2-yn-1-yloxy))benzophenone (2a) and (2-hydroxy-4-(prop-2-yn-1-yloxy))benzophenone (2b), respectively. The copper(I)-catalyzed azide-alkyne cycloaddition (CuAAC) reaction between the compounds 2a/2b and several benzyl azides gave the 1,2,3-triazole-benzophenone derivatives with yields ranging from 35 to 95%. The 1,2,3-triazole-benzophenone derivatives at the concentration of 0.2 μg mL-1 (a no-cytotoxic concentration) exhibited a solar protection factor (SPF) comparable to positive control benzophonen-3 (BP-3). Concerning their antioxidant and cytotoxic effects, the derivatives from 1b showed high in vitro antioxidant effects as well as cytotoxicity against A549 (lung carcinoma), MCF-7 (breast carcinoma), and HT-144 (metastatic melanoma) cell lines, without significant cytotoxicity to a non-cancerous cell line. Derivatives 19, 20, and 24 induced cell death and cell cycle arrest at G1/S in HT-144 melanoma cells.

Carpotroche brasiliensis is a tree native to Brazil, belonging to the family Flacurtiaceae, whose seeds contain a group of cyclopentenyl fatty acids: gorlic (12%), chaulmugric (27%), and hydnocarpic (48.7%). These compounds are considered the main therapeutic agents in the treatment of leprosy. In the present study, a series of novel triazole compounds were obtained by conjugation between hydnocarpic acid and functionalized azides via copper(I)-catalyzed azide-alkyne cycloaddition reaction (CuAAC). Hydnocarpic acid and its derivatives were tested against estrogen-positive breast carcinoma (MCF-7), hepatocellular carcinoma (HepG2), and non-small cell lung cancer (A549) cell lines. The (R)-(1-(pyridin-2-ylmethyl)-1H-1,2,3-triazol-4-yl)methyl-11-(cyclopent-2-en-1-yl)undecanoate (8) displayed promising antiproliferative activity against A549 cells. We demonstrated that this compound selectively inhibited the viability of A549 cell cultures. Furthermore, compound 8 inhibited the clonogenic capacity of A549 cells, and this effect was associated to its ability to inhibit cell cycle progression at G1 phase. These findings indicate that 8 is a promising antitumor agent on A549 cells and support further studies to evaluate the molecular mechanisms underlying its antiproliferative activity. In addition, hydnocarpic acid should be considered as a promising chemical prototype to obtain novel antineoplastic agents.

1,8-Diazabicyclo[5.4.0]undec-7-ene (DBU)-based ionic liquids (ILs) has exhibited a high catalytic activity in the aza-Michael reactions compared to conventional catalysts and with imidazole-based ILs. In the present work DBU-based ILs showed high catalytic potential for aza-Michael addition of aromatic amines to 2-cyclohexen-1-one under solvent-free condition. Electrospray ionization-mass spectrometry (ESI-MS) and density functional theory studies have been carried out to provide an effective activation mode of DBU-based ILs in aza-Michael addition. Our results show that both the presence of the acid hydrogen in the IL and the ability of the anion to carry out a hydrogen bond with the −NH2 group of the arylamine are fundamental for the reaction catalysis. The catalytic model proposed can be used for the rational development of new ILs with excellent catalytic properties.

Nematode is a major problem in agriculture, the effective way to control this pest is through chemical control, but the efficient molecules present in the market have great toxicity to mammals and birds. Thus, there is a constant demand for the development of new nematicide molecules. This study describes the synthesis of 21 novel esters derived from norbornadiene and evaluation of their potential activity against Meloidogyne javanica. The esters 5-25 presented 50% mortality of the nematodes. The acid 3 and the ester 4 caused 96 and 93% mortality of the nematodes, respectively. The lethal concentration to kill 50% of the nematodes (LD50) were determined as being 11.8 µg mL-1 for the acid 3 and 99.4 µg mL-1 for the ester 4. According to the results obtained it is believed that polarity seems to be a key factor for the higher activity of compound 3 compared to structurally similar ester derivatives.

This study evaluated different methods of extraction based on quick, easy, cheap, effective, rugged and safe (QuEChERS) method for analysis of the antibiotics ceftiofur, cloxacillin and enrofloxacin in milk using ultra-performance liquid chromatography-tandem mass spectrometry. The QuEChERS acetate method has been shown to be inefficient for extracting such antibiotics. The optimized QuEChERS method presented excellent recoveries, from 95 to 99%. A complete factorial design was used to evaluate the effects of variables of the clean-up step: anhydrous octadecylsilane (C18), primary secondary amine (PSA) and sodium acetate (NaAc). Linearity (R2) above 0.96 was achieved for all compounds. Accuracy and precision were assessed by recovery. Accuracy was 91-99%. Intraday precision with relative standard deviations (RSD) lower than 12.3% and interday precision lower than 12.4% were obtained. Limits of detection (LOD) and quantification (LOQ) were obtained between 1.4-6.8 and 1.5-8.7 µg L-1, respectively. The applicability was evaluated using 91 real milk samples.

The present investigation describes the synthesis of a series of novel triazole derivatives from 4,4'-dihydroxybenzophenone along with their elastase inhibitory activity. The 1,2,3-triazoles were obtained via the copper(I)-catalyzed azide-alkyne cycloaddition reaction (CuAAC), also known as click reaction, between bis(4-(prop-2-yn-1-yloxy))benzophenone and several benzyl azides. It was found that five derivatives exhibited significant inhibitory effects, presenting half maximal inhibitory concentration (IC50) values in the range of 16.6 to 72.1 µM. The most active compound, namely bis(4-(1-(4-iodobenzyl)-1H-1,2,3-triazol-4-yl)methoxy)benzophenone (IC50 = 16.6 ± 1.9 µM), was found to bind to elastase with the inhibition constant (Ki) of 11.12 µM, thereby illustrating competitive inhibitory behavior. Further, docking investigations provided insights on the possible binding mode of the most active compound with the elastase.

In this study, we investigated the chemical compositions and antioxidant and antimicrobial activities of propolis produced by the stingless bee Frieseomelitta longipes and the honeybee Apis mellifera collected from colonies in North Brazil. In terms of volatile composition, both mono- and sesquiterpenes were detected in the propolis of F. longipes while only sesquiterpenes were detected in that of A. mellifera. Out of 50 volatiles identified in all samples, 26 were found exclusively in F. longipes propolis and 8 were found exclusively in A. mellifera propolis. The chemical profiles of the propolis extracts were determined by atmospheric pressure chemical ionization-mass spectrometry and liquid chromatography-electrospray ionization-tandem mass spectrometry allowed to identify several prenylated benzophenones. A. mellifera extracts exhibited major antioxidant activity as assessed by the 2,2-diphenyl-1-picrylhydrazyl method and all extracts exhibited antioxidant activity as assessed by the β-carotene/linoleic acid method. The ethanolic extracts of the propolis showed promisor activity against all tested microorganisms.

Antioxidants are used to increase the shelf life of food and oils. The most common extraction method of antioxidants from natural sources is the use of organic solvents, like methanol and ethanol. Evaporation of all the organic solvent is necessary to prevent health diseases. In this study, we present a new "organic solvent-free" method to extract antioxidants, which uses canola oil as extraction solvent to incorporate natural antioxidants from oregano and ginger without the use of organic solvent. The oil solvent extraction capacity was assessed by assays of oxygen radical absorbance capacity method for hydrophilic (721.9 ± 10.5 and 89.0 ± 2.5 µmol TE g-1 to canola oil with oregano and ginger, respectively) and lipophilic (118.8 ± 7.4 and 48.2 ± 9.7 µmol TE g-1 to canola oil with oregano and ginger, respectively) compounds, oxidation test (Oxitest®) (1,434 and 1,018 minutes to canola oil with oregano and ginger, respectively) and thiobarbituric acid reactive substances (0.01 ± 0.02 and 0.11 ± 0.06 mg MA g-1 to canola oil with oregano and ginger, respectively). Results provide evidence of the efficiency of canola oil as antioxidants extractor. Nine antioxidant compounds from canola oil incorporated with antioxidants compounds were identified using high performance liquid chromatography tandem mass spectrometry.

Indigenous bacteria isolated from a crude oil sample from a deep water reservoir in the Pampo Sul Oilfield (Campos Basin-RJ, Brazil) were previously classified as strains of B. pumilus. However, their enzymatic activities with fluorogenic probes and rates of petroleum biodegradation were completely different. Some of the bacteria depleted n-alkanes, whereas others did not. Aromatic compounds reported to be recalcitrant were also biodegraded by some of these Bacillus strains, revealing their outstanding ability to deplete petroleum. Further classification using matrixassisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF MS) followed by statistical analysis revealed that these strains could be clustered into three different groups, consistent with their enzymatic activity evaluation. A more accurate phylogenetic analysis using gyrB gene sequences confirmed the MALDI-TOF MS classification of three groups of strains and identified them as Bacillus safensis, B. cereus and B. thuringiensis.

The compound extraction is an important step before analyzing composition of samples with antioxidant capacity. Several extraction conditions can be employed (temperature, polarity of solvent and extraction time, for example), and the chosen variables exert great influence upon final results. Thus, in order to execute an efficient extraction, it is needed to manage them with rigor. In this work, a new device was designed and tested. The Prompt, TOugh and eCO-friendly (PTOCO) system is the first equipment in mini-scale that allows a good control of antioxidants extraction conditions. It is a simple and cheap device that only needs small amounts of sample and solvent to obtain sufficient volumes of extract for application in routine analytical methods. Twenty experiments from an experimental design were executed using only 0.5 g of oregano and 60 mL of water. The total antioxidant capacity assays, as well as the mass spectra, confirmed the extraction efficiency.

Cada matriz alimentar é única. Os antioxidantes endógenos de um produto de panificação não estudados podem mostrar diferentes respostas para atividade antioxidante total (TAA)/resistência a oxidação forçada (ROF) do que é esperado para outros alimentos reportados na literatura. Neste contexto, um design Box-Behnken e estudos de correlação foram aplicados para obter mais informações sobre como compostos antioxidantes específicos afetam o TAA/ROF em pães com sementes de chia e folhas de cenoura. Hipóteses de sinergismo/antagonismo entre os compostos estudados foram elucidadas para tentar justificar os resultados obtidos. Neste tipo específico de amostra, carotenóides e colesterol tiveram as maiores relações com resultados de ensaios de TAA, bem como com pontos de indução provenientes do equipamento Oxitest®, enquanto que α-tocoferol e fitosteróis mostraram correlações negativas. Compostos fenólicos não tiveram nenhuma influência no sistema porque o cozimento em alta temperatura das amostras destruiu grande parte desses analitos.

Each food matrix is unique. Thus, the endogenous antioxidants of an underexplored bakery product might show different responses regarding free radical scavenging/resistance to forced oxidation than what is expected for other foods previously reported in the literature. In this context, a Box-Behnken design and correlation studies were applied in order to obtain more information about how specific antioxidants affect the total antioxidant activity (TAC) and the degree of forced oxidation in white breads with chia seeds and carrot leaves. Hypotheses of synergism/antagonism between the studied compounds were also elucidated in order to justify the obtained results. In this specific sample type, carotenoids and cholesterol showed the greatest relationships with results from TAC assays, as well with induction points using Oxitest® equipment, while α-tocopherol and phytosterols showed negative correlations. Phenolic compounds did not have any influence on the system because the baking procedure at high temperature had severe impacts on them.

Sílica organicamente modificada e molecularmente impressa foi preparada através de um procedimento sol-gel simples, e avaliada como sorvente específico para extração em fase sólida (Solid Phase Extraction, SPE) de fenobarbital em amostras aquosas e forenses. As propriedades analíticas dessa sílica molecularmente impressa (MIS, molecularly imprinted silica) foram inicialmente avaliadas e o material determinado como específico para as espécies-alvo: o fator de impressão IF, medido como a razão entre o pico do fenobarbital em cromatogramas de MIS e NIS (sílica não-impressa) foi estimado como 58. Este valor é consideravelmente maior que aquele apresentado normalmente para sorventes de impressão convencional baseados em metacrilatos e sugere que interações não-específicas analito/sorvente são insignificantes no MIS. O material foi aplicado no isolamento de fenobarbital de amostras aquosas e plasma; limites de detecção de 10 e 62 µg mL-1, respectivamente, foram encontrados para essas amostras.

A molecularly imprinted organically modified silica was prepared through a simple sol-gel procedure, and evaluated as specific sorbent for solid-phase extraction (SPE) of phenobarbital from aqueous and forensic samples. The analytical properties of the molecularly imprinted silica (MIS, non-imprinted sílica) were initially evaluated and the MIS was found to be specific towards the target species: the imprinting factor IF, measured as the ratio between phenobarbital peak areas in the MIS and NIS chromatograms, was estimated as 58. This value is considerably higher than those usually found for conventional methacrylate-based molecularly imprinted sorbents and suggests that non-specific analyte/sorbent interactions are insignificant in the MIS. This material is applied to the isolation of phenobarbital from aqueous samples and plasma; detection limit of 10 and 62 µg mL-1 was achieved for the former samples, respectively.