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Sulfamoyl-triazolyl-carboxamides were synthesized using DBU as a catalyst, and their molecular docking and MPO activity analyses were performed.

Pyrazoles represent a significant class of heterocyclic compounds that exhibit pharmacological properties. The present study aimed to investigate the antioxidant potential of pyrazol derivative compounds in brain of mice in vitro and the effect of pyrazol derivative compounds in the oxidative damage and toxicity parameters in mouse brain and plasma of mice. The compounds tested were 3,5-dimethyl-1-phenyl-4-(phenylselanyl)-1H-pyrazol (1a), 3,5-dimethyl-4-(phenylselanyl)-1H-pyrazole (2a), 4-((4-methoxyphenyl)selanyl)-3,5-dimethyl-1-phenyl-1H-pyrazole (3a), 4-((4-chlorophenyl)selanyl)-3,5-dimethyl-1-phenyl-1H-pyrazole (4a), 3,5-dimethyl-1-phenyl-4-(phenylthio)-1H-pyrazole (1b), 3,5-dimethyl-4-(phenylthio)-1H-pyrazole (2b), 4-((4-methoxyphenyl)thio)-3,5-dimethyl-1-phenyl-1H-pyrazole (3b), 4-((4-chlorophenyl)thio)-3,5-dimethyl-1-phenyl-1H-pyrazole (4b), and 3,5-dimethyl-1-phenyl-1H-pyrazole (1c). In vitro, 4-(arylcalcogenyl)-1H-pyrazoles, at low molecular range, reduced lipid peroxidation and reactive species in mouse brain homogenates. The compounds also presented ferric-reducing ability as well nitric oxide-scavenging activity. Especially compounds 1a, 1b, and 1c presented efficiency to 1,1-diphenyl-2-picryl-hydrazyl-scavenging activity. Compounds 1b and 1c presented 2,20 -azino-bis(3-ethylbenzthiazoline-6-sulfonic acid)-scavenging activity. In vivo assays demonstrated that compounds 1a, 1b, and 1c (300 mg/kg, intragastric, a single administration) did not cause alteration in the of δ-aminolevulinic acid dehydratase activity, an enzyme that exhibits high sensibility to prooxidants situations, in the brain, liver, and kidney of mice. Compound 1c reduced per se the lipid peroxidation in liver and brain of mice. Toxicological assays demonstrate that compounds 1a, 1b, and 1c did not present toxicity in the aspartate aminotransferase, alanine aminotransferase, urea, and creatinine levels in the plasma. In conclusion, the results demonstrated the antioxidant action of pyrazol derivative compounds in in vitro assays. Furthermore, the results showed low toxicity of compounds in in vivo assays.

4-(Arylchalcogenyl)-1H-pyrazoles containing selenium or sulfur (0.001–50 mg/kg) were investigated regarding the intragastric route effect (ig) administration on nociception in mice. In this study, nociception and inflammation were induced by chemical agents such as formalin (0.92%), sodium l-glutamate 1-hydrate (20 μmol), croton oil (2.5%), acetic acid (1.6%) and thermic model with a hot plate test. Compounds 1a–c had the ability to reduce licking time in both phases (neurogenic and inflammatory) of the formalin test and glutamate. Only compounds 1a and 1b had the ability to reduce the number of abdominal writhes caused by acetic acid. The same was observed with the positive control celecoxib. To evaluate the possible anti-inflammatory activity of compounds 1a–c, the induction of paw edema by formalin and ear edema by croton oil was performed. For the inflammation induced by formalin, significant effects were observed from the dose of 0.1 mg/kg (1a–b) and 10 mg/kg (1c). In the ear edema test, it can be observed that only compound 1a had a significant effect. In the hotplate test, all the compounds had the ability to reduce the latency time. The results demonstrated that acute antinociceptive and anti-inflammatory effects of 4-(arylchalcogenyl)-1H-pyrazoles 1a is better than compared with the compound 1b and 1c in mice. This resulted in these molecules attracting the interest of researchers to perform future studies to develop new drugs to treat pain and inflammatory clinical conditions.

Herein, we describe our results on the determination of the chemical profile of the essential oil (EO) of flowers from Tagetes minuta L. grown in Southern Brazil. The major component of the EO is (Z)-tagetone 1 (70.64% w/w). Thiotagetone 6, a semi-synthetic derivative, was prepared from 1 in 82% yield. Compounds 1 and 6 and the EO were evaluated for their antioxidant and antifungal activities in vitro. All the tested samples presented antioxidant effect in scavenging radical and in the lipid peroxidation assays. A good antifungal activity against Candida lipolityca, Candida parapsilosis, Trichosporon asahii and Sphaceloma ampelinum was observed. (Z)-Tagetone 1 inhibited the mycelia growth of S. ampelinum around 80% at 6 days. No acute toxicity (200 mg/kg) was observed in mice for the EO or the compounds 1 and 6. The lack of toxicity is an indicative for additional studies aiming their potential therapeutic use.

An efficient copper-catalyzed multicomponent reaction was developed for the synthesis of (arylselanyl)- or (arylsulfenyl)-alkyl-1,2,3-triazolo-1,3,6-triazonines. The products were obtained in moderate to excellent yields via the reaction of o-phenylenediamine, 2-azidobenzaldehyde and different arylchalcogenyl alkynes using catalytic copper iodide in 1,4-dioxane at 100 °C. The reactions tolerated a range of substituents on the arylchalcogenyl alkynes and proved to be an efficient methodology for the combinatorial synthesis of new selenium or sulfur-containing triazonine derivatives.

We present here the synthesis of novel (Z)-2-organylselanyl ketoximes by nucleophilic substitution reaction of E/Z mixtures of 2-bromo ketoximes with nucleophilic species of selenium, which were generated in situ by simple cleavage of diorganyl diselenides with NaBH4 using ethanol/THF as solvent. The new 2-organylselanyl ketoximes were synthesized in moderate to good yields and with selectivity for the (Z)-configuration. The synthesized (Z)-2-arylselanylacetophenone oximes were submitted to the Beckmann rearrangement, furnishing the corresponding N-aryl-2-(selanyl)acetamides. (Z)-1-Phenyl-2-(phenylselanyl) ketoxime has antifungal activity against Sphaceloma ampelinum and a good level of antioxidant activity in vitro in DPPH, ABTS, FRAP and lipid peroxidation assays.

We describe herein an efficient protocol to synthesize selanyl-substituted pyrazoles by cyclocondensation and copper-catalyzed direct CH bond selenation reactions. The products were obtained in moderate to excellent yields by the one-pot multicomponent reactions of hydrazines, 1,3-diketones and diorganyl diselenides, using catalytic amounts of copper bromide and bipyridine. These reactions tolerated a range of substituents in the starting materials and proved to be an efficient methodology for combinatorial synthesis of new selenium-containing pyrazoles with potential applications in biological studies.

Several pathologies, such as pain and inflammation, are modulated by different pathways, making it necessary to develop drugs capable of modulating different pathways. Based on that, we investigated the antinociceptive and anti-inflammatory effect of 3-(4-chlorophenylselanyl)-1-methyl-1H-indole (CMI), as well as the systems involved in these actions. This study evaluated the antinociceptive and anti-inflammatory effects of CMI [0.0001–10 mg/kg administered intragastrically (i.g.)] in the formalin, glutamate, hot plate, ear edema induced by croton oil and paw edema induced by formalin tests. In addition, to investigate the mechanism of action, mice were pre-treated with antagonists of adenosinergic, monoaminergic and opioid systems before administration of CMI. The selenium-containing compound decreased the paw licking and biting time in the formalin and glutamate tests, increased the response latency in hot plate test, without ambulatory changes, evaluated in the open field test. CMI was able to reduce both paw and ear edema induced by formalin and croton oil, respectively. Additionally the antinociceptive effect of CMI (0.01 mg/kg) was blocked when mice were pretreated with the antagonists: SCH23390 [D1-receptor antagonist, 0.05 mg/kg, intraperitoneally (i.p.)], WAY100635 (5-HT1A-receptor antagonist, 0.7 mg/kg, i.p.), ondansetron (5-HT3-receptor antagonist, 0.5 mg/kg, i.p.), ketanserin (5-HT2A/2C-receptor antagonist, 0.3 mg/kg, i.p.), naloxone (non-selective antagonist 1 mg/kg, i.p.), caffeine (non-selective antagonist, 3 mg/kg, i.p.) and prazosin (α1-receptor antagonist, 0.15 mg/kg, i.p). These results demonstrate that the antinociceptive effect of CMI is mediated by monaminergic, opioidergic and adenosinergic modulations and can be a promising molecule capable of modulating different pathways for the treatment of pain and inflammation.

Background: The main constituents of Cymbopogonnardus (L) Rendle and C. citratus (DC) Stapfessential oils are (R)-citronellal and citral, respectively. Organochalcogen compounds can boost the biological activities of natural products. Methods: Several chalcogen-containing nitrones derived from (R)-citronellal and citral were prepared and evaluated for their antimicrobial and antioxidant activities. The antimicrobial activity was evaluated by the disc diffusion test and the antioxidant properties were evaluated in vitro by DPPH (1,1-diphenyl-2-picryl-hydrazyl), ABTS (2,2′-azino-bis(3-ethylbenzthiazoline-6-sulfonic acid), and FRAP (ferric ion reducing antioxidant power) assays. Results: In the antimicrobial assay, (E)-N,3,7-trimethyl-3-(phenylthio)oct-6-en-1-imine oxide 5c exhibited halos between 21.5 mm (Escherichia coli O157:H7) and 26.0 mm (Listeria monocytogenes), while (E)-N,3,7-trimethyloct-6-en-1-imine oxide 5d presented halos between 22.5 mm (E. coli O157:H7) and 31.0 mm (L. monocytogenes). (E)-N,3,7-Trimethyl-2-(phenylthio)oct-6-en-1-imine oxide 5a showed the lowest minimal inhibitory concentration (MIC) value against Bacillus cereus (0.48 mM), and 5c was the most potent bactericide, with a minimal bactericidal concentration (MBC) of 0.52 mM for E. coli O157:H7. In the antioxidant assays, 5c, 5d, and 10 ((E)-3,7-dimethyl-2-(phenylselanyl)oct-6-enal oxime) were the most actives in the DPPH, ABTS, and FRAP assays, respectively. Conclusions: The presence of a phenylthio group in the nitrone increases its antimicrobial activity against Gram-positive and Gram-negative foodborne pathogens in the disk diffusion test and the antioxidant activity in vitro.

Psidium cattleianum Sabine (Myrtacea) is rich in vitamin C and phenolic compounds, including epicatechin and gallic acid as the main components.To evaluate the antifungal and antioxidant capacity in vitro of the essential oil of araçá (EOA). The acute toxicity of the EOA also was evaluated in mice.The leaves of the P. cattleianum were extracted by steam distillation. The antioxidant capacity was evaluated by in vitro tests [1,1-diphenyl-2-picryl-hydrazyl (DPPH), 2,2-azinobis(3-ethylbenzothiazoline-6-sulfonate) (ABTS), ferric ion reducing antioxidant power (FRAP), linoleic acid oxidation, thiobarbituric acid reactive species (TBARS)], and ex vivo analysis [TBARS, δ-aminulevunilate dehydratase (δ-Ala-D) and catalase activity, non-protein thiols (NPSH), and ascorbic acid levels]. The toxicity was studied in mice by a single oral administration of EOA; and the antifungal activity was performed with five strains of fungi.The EOA exhibited antioxidant activity in the FRAP assay and reduced lipid peroxidation in the cortex (Imax = 32.90 ± 2.62%), hippocampus (IC50 = 48.00 ± 3.00 µg/ml and Imax = 32.90 ± 2.62%), and cerebellum (Imax = 45.40 ± 14.04%) of mice. Acute administration of the EOA by the oral route did not cause toxicological effects in mice (LD50 500 µg/ml). The EOA also showed antifungal activity through of the determination minimum inhibitory concentration (MIC) values ranging from 41.67 ± 18.04 to 166.70 ± 72.17 µg/ml for tested strains.The results of present study indicate that EOA possess antioxidant properties, antifungal and not cause toxicity at tested doses.

Imine-modified silicas were synthesized by the reaction of the essential oil of Eucalyptus citriodora , 3-aminopropyltriethoxysilane and tetraethylorthosilicate by different methods. The imine supported on silica was characterized by FT-IR-spectroscopy using the attenuated total reflection (ATR) technique, the Brunauer–Emmett–Teller (BET) method and thermogravimetric analysis (TGA). These silicas have shown a large amount of organic matter incorporated on the surface, which affects their textural properties. The hydrolysis reaction of the imine-modified silica leads to the formation of products different from those expected.

We describe here a simple method to synthesize 4-arylselanylpyrazoles by reaction of α-arylselanyl-1,3-diketones with arylhydrazines using glycerol as solvent at 60 °C under N2 atmosphere. This is a direct cyclocondensation reaction performed with α-arylselanyl-1,3-diketones and arylhydrazines bearing electron-withdrawing and electron-donating groups affording the corresponding 4-arylselanylpyrazoles in moderate to good yields.

The present study aimed to evaluate the in vitro antimicrobial action of Origanum vulgare, Origanum majorana, Mentha piperita and Rosmarinus officinalis on Pythium insidiosum oomycete zoospores. The antimicrobial activity evaluation was performed by the broth microdilution method according to CSLI M38-A2 documentation adapted to phytopharmaceuticals. Twenty-two P. insidiosum isolates were evaluated, and the minimum inhibitory concentration was determined at 100 % growth inhibition. All P. insidiosum isolates evaluated showed a minimum inhibitory concentration ranging from 0.05 to 1.75 mg/mL when O. vulgare oil was used and from 0.11 to 3.5 mg/mL for O. majorana, M. piperita and R. officinalis oils. The results obtained indicate that the essential oils tested showed antimicrobial activity on P. insidiosum, with O. vulgare essential oil showing the best performance. These findings emphasize the potential use of plant essential oils as control agents in P. insidiosum infections; further research, however, is needed so as the in vivo activity of these oils can also be evaluated.