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O objetivo deste estudo foi identificar substâncias adicionadas ao biodiesel capazes de minimizar as reacoes de oxidacao, impedindo o inicio ou antecipando o fim das reacoes de oxidacao. A espectroscopia EPR foi utilizada para identificar e caracterizar qualitativamente esses possiveis compostos antioxidantes, usando o metodo UV-VIS, baseado na extincao do radical livre DPPH • (2,2-difenil-1-picril-hidrazil) pelos antioxidantes, que produz uma diminuicao na absorbância a 515 nm, com a proposta de comparacao e validacao dos dados EPR. Pelo menos, para atestar a eficacia dos antioxidantes adicionados ao biodiesel, foi utilizado o Metodo Rancimat (EN 14112), que determina a estabilidade a oxidacao do combustivel. Os melhores resultados foram obtidos pelo redoxoma 17 (R17), melhor que o redoxoma 01 (R01), tambem conhecido como tempol (4-hidroxi-2,2,6,6-tetrametilpiperidina-1-oxil), conhecido como bom antioxidante e ja patenteado como antioxidante do biodiesel.

HSV disease is distributed worldwide. Anti-herpesvirus drugs are a problem in clinical settings, particularly in immunocompromised individuals undergoing herpes simplex virus type 1 infection. In this work, 4-substituted-1,2,3-1H-1,2,3-triazole linked nitroxyl radical derived from TEMPOL were synthesized, and their ability to inhibit the in vitro replication of HSV-1 was evaluated. The nitroxide derivatives were characterized by infrared spectroscopy and elemental analysis, and three of them had their crystal structures determined by single-crystal X-ray diffraction. Four hybrid molecules showed important anti-HSV-1 activity with IC50 values ranged from 0.80 to 1.32 µM. In particular, one of the nitroxide derivatives was more active than Acyclovir (IC50 = 0.99 µM). All compounds tested were more selective inhibitors than the reference antiviral drug. Among them, two compounds were 4.5 (IC50 0.80 µM; selectivity index CC50/IC50 3886) and 7.7 times (IC50 1.10 µM; selectivity index CC50/IC50 6698) more selective than acyclovir (IC50 0.99 µM; selectivity index CC50/IC50: 869). These nitroxide derivatives may be elected as leading compounds due to their antiherpetic activities and good selectivity.

Tuberculosis, caused by Mycobacterium tuberculosis (M. tuberculosis), is still responsible for a large number of fatal cases, especially in developing countries with alarming rates of incidence and prevalence worldwide. Mycobacterium tuberculosis has a remarkable ability to develop new resistance mechanisms to the conventional antimicrobials treatment. Because of this, there is an urgent need for novel bioactive compounds for its treatment. The dehydroquinate dehydratase II (DHQase II) is considered a key enzyme of shikimate pathway, and it can be used as a promising target for the design of new bioactive compounds with antibacterial action. The aim of this work was the construction of QSAR models to aid the design of new potential DHQase II inhibitors. For that purpose, various molecular modeling approaches, such as activity cliff, QSAR models and computer-aided ligand design were utilized. A predictive in silico 4D-QSAR model was built using a database comprising 86 inhibitors of DHQase II, and the model was used to predict the activity of the designed ligands. The obtained model proved to predict well the DHQase II inhibition for an external validation dataset ( $$ Q^{2}_{\text{ext}} $$ = 0.72). Also, the Activity Cliff analysis shed light on important structural features applied to the ligand design.

The water mol­ecule connects the mol­ecules in the crystal packing. The crystal structure exhibits N—H⋯O, O—H⋯O and O—H⋯N inter­actions, resulting in the formation of a three-dimensional framework., In the mol­ecular structure of the title compound, C10H10N4O2·H2O, the angle between the triazole and arene rings is 87.39 (5)°. The water of crystallization connects the mol­ecules in the crystal packing. The crystal structure exhibits N—H⋯O, O—H⋯O and O—H⋯N inter­actions, resulting in the formation of a three-dimensional framework. The inter­molecular inter­actions were identified and qu­anti­fied using Hirshfeld surface analysis.

Despite the existing antibiotics, antimicrobial resistance is a major challenge. Consequently, the development of new drugs remains in great demand. Quinones is part of a broad group of molecules that present antibacterial activity besides other biological properties. The main purpose of this study was to evaluate the antibiofilm activities of synthetic N,O-acetals derived from 2-amino-1,4-naphthoquinone [7a: 2-(methoxymethyl)-amino-1,4-naphthoquinone; 7b: 2-(ethoxymethyl)-amino-1,4-naphthoquinone; and 7c: 2-(propynyloxymethyl)-amino-1,4-naphthoquinone] against methicillin-resistant Staphylococcus aureus (MRSA). The derivatives 7b and 7c, specially 7b, caused strong impact on biofilm accumulation. This inhibition was linked to decreased expression of the genes fnbA, spa, hla and psmα3. More importantly, this downregulation was paralleled by the modulation of global virulence regulators. The substitution of 2-ethoxymethyl (7b) in comparison with 2-propynyloxymethyl (7c) enhanced sarA-agr inhibition, decreased fnbA transcripts (positively regulated by sarA) and strongly impaired biofilm accumulation. Indeed, 7b triggered intensive autolysis and was able to eliminate vancomycin-persistent cells. Consequently, 7b is a promising molecule displaying not only antimicrobial effects, but also antibiofilm and antipersistence activities. Therefore, 7b is a good candidate for further studies involving the development of novel and more rational antimicrobials able to act in chronic and recalcitrant infections, associated with biofilm formation.

Melatonin and its indoles derivatives are central in the synchronization of malaria parasites. In this research, we discovered that melatonin is unable to increase the parasitemia in the human malaria Plasmodium falciparum that lacks the kinase PfeIK1. The PfeIK1 knockout strain is a valuable tool in the screening of indol‐related compound that blocks the melatonin effect in wild‐type (WT) parasite development. The assays were performed by using flow cytometry with simultaneous labeling for mitochondria viability with MitoTracker Deep Red and nucleus staining with SYBR Green. We found that Melatotosil leads to an increase in parasitemia in P. falciparum and blocks melatonin effect in the WT parasite. Using microscopy imaging system, we found that Melatotosil at 500 nM is able to induce cytosolic calcium rise in transgenic PfGCaMP3 parasites. On the contrary, the compound Triptiofen blocks P. falciparum cell cycle with IC50 9.76 µM ± 0.6, inhibits melatonin action, and does not lead to a cytosolic calcium rise in PfGCaMP3 parasites. We also found that the synthetic indol‐related compounds arrested parasite cycle for PfeIK1 knockout and (WT) P. falciparum (3D7) in 72 hours culture assays with the IC50 values slighting lower for the WT strain. We concluded that the kinase PfeIK1 is central for melatonin downstream signaling pathways involved in parasite cell cycle progression. More importantly, the indol‐related compounds block its cycle as an upstream essential mechanism for parasite survival. Our data clearly show that this class of compounds emerge as an alternative for the problem of resistance with the classical antimalarials.

Natural products are considered an important source of bioactive compounds especially in biodiversity-rich countries like Brazil. The identification of potential targets is crucial to the development of drugs from natural sources. In this context, in silico methodologies, such as inverse virtual screening (target fishing), are interesting tools as they are a rational and direct method that reduces costs and experimental time. Among the species of Brazilian biomes, Bryophyllum pinnatum (Lam.) Oken, native to Madagascar, is widely used by the population to treat inflammation conditions. It has a remarkable presence of flavonoids, including quercetin 3-O-α-L-arabinopyranosyl-(1→2)-O-α-L-rhamnopyranoside (1), considered one of its major compounds. However, until now there were no studies addressing its putative mechanism of action and explaining its pharmacological action. The enzyme PDE4B, known as an antiinflammatory protein, was indicated as a promising target by target fishing methods. This activity was confirmed by in vitro enzymatic inhibition, and an expressive selectivity of PDE4B over PDE4A was demonstrated. The interactions were investigated through molecular dynamics simulations. The results were pioneering, representing an advance in the investigation of the antiinflammatory action of B. pinnatum and confirm the potential of the flavonoid as a chemical extract marker. Also, the flavonoid was shown to be a promising lead for the design of other selective PDE4B blockers to treat inflammatory diseases.

HSV disease is distributed worldwide. Anti-herpesvirus drugs are a problem in clinical settings, particularly in immunocompromised individuals undergoing herpes simplex virus type 1 infection. In this work, 4-substituted-1,2,3-1H-1,2,3-triazole linked nitroxyl radical derived from TEMPOL were synthesized, and their ability to inhibit the in vitro replication of HSV-1 was evaluated. The nitroxide derivatives were characterized by infrared spectroscopy and elemental analysis, and three of them had their crystal structures determined by single-crystal X-ray diffraction. Four hybrid molecules showed important anti-HSV-1 activity with IC

Tuberculosis, caused by Mycobacterium tuberculosis (M. tuberculosis), is still responsible for a large number of fatal cases, especially in developing countries with alarming rates of incidence and prevalence worldwide. Mycobacterium tuberculosis has a remarkable ability to develop new resistance mechanisms to the conventional antimicrobials treatment. Because of this, there is an urgent need for novel bioactive compounds for its treatment. The dehydroquinate dehydratase II (DHQase II) is considered a key enzyme of shikimate pathway, and it can be used as a promising target for the design of new bioactive compounds with antibacterial action. The aim of this work was the construction of QSAR models to aid the design of new potential DHQase II inhibitors. For that purpose, various molecular modeling approaches, such as activity cliff, QSAR models and computer-aided ligand design were utilized. A predictive in silico 4D-QSAR model was built using a database comprising 86 inhibitors of DHQase II, and the model was used to predict the activity of the designed ligands. The obtained model proved to predict well the DHQase II inhibition for an external validation dataset ([Formula: see text] = 0.72). Also, the Activity Cliff analysis shed light on important structural features applied to the ligand design.

Background: Since the influenza virus is the main cause of acute seasonal respiratory infections and pandemic outbreaks, antiviral drugs are critical to mitigate infections and impair chain of transmission. Neuraminidase inhibitors (NAIs) are the main class of anti-influenza drugs in clinical use. Nevertheless, resistance to oseltamivir (OST), the most used NAI, has been detected in circulating strains of the influenza virus. Therefore, novel compounds with anti-influenza activity are necessary. Objective: To verify whether the NA from influenza A and B virus is susceptible to the compound 4-(4- phenyl-1H-1,2,3-triazol-1-yl)-2,2,6,6-tetramethylpiperidine-1-oxyl (Tritempo). Methods: Cell-free neuraminidase inhibition assays were performed with Tritempo, using wild-type (WT) and OST-resistant influenza strains. Cell-based assays in MDCKs were performed to confirm Tritempo`s antiviral activity and cytotoxicity. Multiple passages of the influenza virus in increasing concentrations of our compound, followed by the sequencing of NA gene and molecular docking, were used to identify our Tritempo’s target. Results/Discussion: Indeed, Tritempo inhibited the neuraminidase activity of WT and OSTresistant strains of influenza A and B, at the nanomolar range. Tritempo bound to WT and OST-resistant influenza NA isoforms at the sialic acid binding site with low free binding energies. Cell-free assays were confirmed using a prototypic influenza A infection assay in MDCK cells, in which we found an EC50 of 0.38 µM, along with very low cytotoxicity, CC50 > 2,000 µM. When we passaged the influenza A virus in the presence of Tritempo, a mutant virus with the G248P change in the NA was detected. This mutant was resistant to Tritempo but remained sensitive to OST, indicating no cross-resistance between the studied and reference drugs. Conclusion: Our results suggest that Tritempo’s chemical structure is a promising one for the development of novel antivirals against influenza.

Candidiasis is a serious public health problem that currently affects not only immunodeficient patients with predisposing conditions, but also immunocompetent individuals. Thus, the search for new antifungal agents is required also due to the emergence of resistant strains and to the side effects of the available drugs. The aim of this study is to evaluate the in vitro antifungal profile of nine synthetic 1,2,3-triazole derivatives against four Candida species of medical importance (C. albicans, C. tropicalis, C. parapsilosis, and C. krusei), as well as to identify their in silico structure-activity relationship. Interestingly, the antifungal susceptibility tests showed the compound 5-methyl-1-(phenylamino)-1H-1,2,3-triazol-4-yl-methanol (2b) with the lowest minimal inhibitory concentration value against C. albicans strain (MIC = 8 μg/mL) similar to other promissing compounds described in the literature. According to our in silico evaluation, some stereoelectronic properties (e.g., higher values of log S and lowest unoccupied molecular orbital energy and lower number of atoms, rotatable bonds and Hydrogen bond acceptors) were correlated with the antifungal activity detected. This series reinforced the potential of 1,2,3-triazole as a promising nucleus in the search for new antifungals and may help on designing new drugs for candidiasis.

Lawsone (1) is a special naphthoquinone that is useful for many applications in various scientific and technological fields. For over 100 years, it has been used as the starting material for the synthesis of a variety of biologically active compounds and materials with interesting properties. In organic synthesis, it has been used in many reactions. This review aims to address the various aspects of its use in organic synthesis.

The crystallography of mono-p-substituted derivatives of 1-(arylamino)-1,2,3-triazole-4-carbohydrazides, 1 (X = H), 2 (F), 3 (Cl) and 4 (Br), and a 2,5-dichloro (5) analogue, shows the molecular structures to be similar. Distinct hydrogen bonding patterns based on N–H⋯N and N–H⋯O are observed in their crystal structures with 1, having two independent molecules comprising the asymmetric unit, displaying one pattern, 2 and 5 another, and 3 and 4 yet another. Geometry optimisation calculations indicate that any conformational differences in the solid state do not persist in the gas-phase and that no influence of the substituents is seen on the geometric parameters. A natural population analysis, for both experimental and optimised structures, shows that the charge on the triazole-N3 atom is at a maximum for 1, as opposed to 2–5, an observation correlated with its distinctive packing based around a supramolecular synthon not seen in the other structures. For the molecules having electronegative substituents, molecular electrostatic potentials show that the energies of the amine-H4n atoms are reduced for 2 and 5, compared to 3 and 4. A further distinction in 2–5 is indicated by the Hirshfeld surface analysis which highlights the importance of π⋯π interactions in 2 and 5, i.e. with the more electronegative substituents. Clearly, there is interplay between various factors but all correlated with the influence of the electronegativity of the substituent(s).

Background Cardiovascular diseases are the most frequent cause of morbidity and mortality worldwide. Among the most important cardiovascular diseases are atherothrombosis and venous thromboembolism that present platelet aggregation as a key event. Currently, the commercial antiplatelet agents display several undesirable effects, which prompt the search for new compounds with better therapeutic index, more efficient body distribution and mechanism. Methods In this work we characterized in vivo and in vitro the antithrombotic and toxicological profiles of novel antiplatelet N -substituted-phenylamino-5-methyl-1H-1,2,3-triazole-4-carbohydrazides derivatives also comparing them with aspirin. In addition we also analyzed the stability of the more active compound after encapsulation in PLGA or PCL nanoparticles and the release profile of these new nanosystems. Results The biological results revealed not only the selective effect against arachidonic acid-induced platelet aggregation mainly for compounds 2c, 2e and 2 h but also their in vivo active profile on thromboembolism pulmonary animal model with better survival rates (e.g. 82%) than aspirin (33%). The overall toxicological profile was determined by in vitro (MTT reduction tests, neutral red uptake in kidney VERO cells and hemolysis assays) and in vivo (pulmonary embolism) assays that pointed 2c as the most promising derivative with potential as a lead compound. By using the nanoprecipitation technique 2c was loaded into PLGA and PCL nanoparticles showing controlled release profile over 21 days according to our drug release tests. Conclusion According to our results compound 2c is the most interesting derivative for further studies as it showed the best activity and toxicological profile also allowing the nanoencapsulation process. Thus 2c may assist in determining a new potential therapy with favorable pharmacokinetics for treatment of thrombotic disorders.

In this work we report the synthesis, crystal structures, and magnetic behavior of 2p-3d-4f heterospin systems containing the nitroxide radical 4-azido-2,2,6,6-tetramethylpiperidine-1-oxyl radical (N3tempo). These compounds were synthesized through a one-pot reaction by using [Cu(hfac)2], [Ln(hfac)3] (hfac = hexafluoroacetylacetonate, Ln = Dy(III), Tb(III) or Gd(III)), and the N3tempo radical. Depending on the stoichiometric ratio used, the synthesis leads to penta- or trimetallic compounds, with molecular formulas [Cu3Ln2(hfac)8(OH)4(N3tempo)] (Ln = Gd, Tb, Dy) and [CuLn2(hfac)8(N3tempo)2(H2O)2] (Ln = Gd, Dy). The magnetic properties of all compounds were investigated by direct current (dc) and alternating current (ac) measurements. The ac magnetic susceptibility measurements of Tb(III)- and Dy(III)-containing compounds of both families revealed slow relaxation of the magnetization, with magnetic quantum tunneling in zero field.

This paper describes a novel series of N,O-acetals and N,S-acetals (7a-o) derived from 2-amino-1,4-naphthoquinones that were synthesized and evaluated as potential antimicrobial agents. These compounds were obtained in good yields using microwave irradiation, and several of them showed promising antibacterial profiles. Three of our biologically active 2-amino-1,4-naphthoquinone N,O-acetals and N,S-acetals tested against hospital bacterial strains were identified as potential lead compounds. Characterization of all compounds was performed using one-dimensional NMR techniques ((1)H, (13)C-APT), IR spectra, elemental analyses and high-resolution electrospray ionization mass spectrometry (HR-ESI-MS).

A series of 13 D-gluconamides were synthesized in moderate to good yields and evaluated as green scale inhibitors. The crystal structures of two compounds were determined by X-ray crystallography. The compounds 6c and 6d showed a reasonable inhibition of BaSO(4) precipitation from aqueous solution (47% and 51%, respectively) that indicated the potential for these derivatives of δ-gluconolactone.

Two new magnetic copper compounds were obtained using the 4,4,4-trifluoro-1-furoylbutane-1,3-dione (Ftfac) ligand and two nitroxide radicals: 3-pyridyl-4,4,5,5-tetramethylimidazoline-1-oxyl-3-oxide (NITmPy) and 4-hydroxy-2,2,6,6-tetramethylpiperidinyl-N-oxy (Tempol). The complexes with formula [Cu(Ftfac)2(NITmPy)2] (1) and [Cu(Ftfac)2(Tempol)] (2) were structurally characterized by single-crystal X-ray diffraction. In compound 1, the copper ion has a distorted octahedral environment, bound to two NITmpPy ligands through the nitrogen atom of the pyridine ring. In compound 2, the copper ion has a distorted pyramidal environment in which the apical position is occupied by the oxygen atom of the Tempol hydroxyl group. The temperature dependence of the magnetic susceptibility of the two compounds was investigated. It was found that compound 1 presents ferromagnetic interaction (J = 9.1 cm−1) among copper(II) ions and NITmPy radicals. As a result of the interconnection between molecular moieties through H-bonds, compound 2 presents an unusual magnetic behavior with alternating ferro- and antiferromagnetic interactions.

This paper describes the synthesis, antiplatelet and theoretical evaluations of 10 N-substituted-phenylamino-5-methyl-1H-1,2,3-triazole-4-carbohydrazides (2a-j). These compounds were synthesized, characterized and screened for their in vitro antiplatelet profile against human platelet aggregation using arachidonic acid, adrenaline and ADP as agonists. Among NAH derivatives 2a-j, the compounds 2a, 2c, 2e, 2g and 2h were the most promising molecules with significant antiplatelet activity.

Lawsone (1) is a special naphthoquinone that is useful for many applications in various scientific and technological fields. For over 100 years, it has been used as the starting material for the synthesis of a variety of biologically active compounds and materials with interesting properties. In organic synthesis, it has been used in many reactions. This review aims to address the various aspects of its use in organic synthesis.

Bacterial multiresistance is a health problem worldwide that demands new antimicrobials for treating bacterial-related infections. In this study, we evaluated the antimicrobial activity and the theoretical toxicology profile of N-substituted-phenylamino-5-methyl-1H-1,2,3-triazole-4-carbohydrazide derivatives against gram-positive and gram-negative bacteria clinical strains. On that purpose we determined the minimum inhibitory (MIC) and bactericidal (MBC) concentrations, the in vitro cytotoxicity, and in silico risk profiles, also comparing with antimicrobial agents of clinical use. Among the 16 derivatives analyzed, four nitrofurans (N-H-FUR-NO(2), N-Br-FUR-NO(2), N-F-FUR-NO(2), N-Cl-FUR-NO(2)) showed promising MIC and MBC values (MIC = MBC = 1-16 μg/mL). The experimental data revealed the potential of these derivatives, which were comparable to the current antimicrobials with similar bactericidal and bacteriostatic profiles. Therefore, these molecules may be feasible options to be explored for treating infections caused by multiresistant strains. Our in vitro and in silico toxicity reinforced these results as these derivatives presented low cytotoxicity against human macrophages and low theoretical risk profile for irritant and reproductive effects compared to the current antimicrobials (e.g., vancomycin and ciprofloxacin). The molecular modeling analysis also revealed positive values for their theoretical druglikeness and drugscore. The presence of a 5-nitro-2-furfur-2-yl group seems to be essential for the antimicrobial activity, which pointed these acylhydrazone derivatives as promising for designing more potent and safer compounds.

Discovering the mechanisms by which cell signaling controls the cell cycle of the human malaria parasite Plasmodium falciparum is fundamental to designing more effective antimalarials. To better understand the impacts of melatonin structure and function on the cell cycle of P. falciparum , we have synthesized two families of structurally-related melatonin compounds ( 7–11 and 12–16 ). All synthesized melatonin analogs were assayed in P. falciparum culture and their antimalarial activities were measured by flow cytometry. We have found that the chemical modification of the carboxamide group attached at C-3 position of the indole ring of melatonin ( 6 ) was crucial for the action of the indole-related compounds on the P. falciparum cell cycle. Among the melatonin derivatives, only the compounds 12, 13 and 14 were capable of inhibiting the P. falciparum growth in low micromolar IC 50 . These results open good perspectives for the development of new drugs with novel mechanisms of action.

INTRODUCTION The synthesis of aminoquinones and related compounds has attracted considerable attention, because they exhibit a wide spectrum of pharmaceutical activities including antitumor and antimalarial properties 1 . Two general methods are available for the synthesis of aminoquinones 2 : nucleophilic substitution reaction of halo-derivative quinones with amines and direct 1,4-type addition of amines to quinones, with or without Lewis acid conditions under ultrasonic irradiation. As part of an ongoing research program on the synthesis of new quinone derivatives and on the basis of our experience in the field of the use of carbohydrates in organic synthesis, we herein report an extension of the second approach 3 which led to three novel isoquinoline-5,8-quinone derivatives 1a-c, possessing a carbohydrate chain at C-7position of the quinone ring.

Snake venoms are complex mixtures of proteins of both enzymes and nonenzymes, which are responsible for producing several biological effects. Human envenomation by snake bites particularly those of the viperid family induces a complex pathophysiological picture characterized by spectacular changes in hemostasis and frequently hemorrhage is also seen. The present work reports the ability of six of a series of 1,2,3-triazole derivatives to inhibit some pharmacological effects caused by the venoms ofBothrops jararacaandLachesis muta.In vitroassays showed that these compounds were impaired in a concentration-dependent manner, the fibrinogen or plasma clotting, hemolysis, and proteolysis produced by both venoms. Moreover, these compounds inhibited biological effectsin vivoas well. Mice treated with these compounds were fully protected from hemorrhagic lesions caused by such venoms. But, only theB. jararacaedema-inducing activity was neutralized by the triazoles. So the inhibitory effect of triazoles derivatives against somein vitroandin vivobiological assays of snake venoms points to promising aspects that may indicate them as molecular models to improve the production of effective antivenom or to complement antivenom neutralization, especially the local pathological effects, which are partially neutralized by antivenoms.

Tempol (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxyl) and other cyclic nitroxides have been shown to inhibit the chlorinating activity of myeloperoxidase (MPO) in vitro and in cells. To examine whether nitroxides inhibit MPO activity in vivo we selected acute carrageenan-induced inflammation on the rat paw as a model. Tempol and three more hydrophobic 4-substituted derivatives (4-azido, 4-benzenesulfonyl, and 4-(4-phenyl-1H-1,2,3-triazol-1-yl)) were synthesized, and their ability to inhibit the in vitro chlorinating activity of MPO and carrageenan-induced inflammation in rat paws was evaluated. All of the tested nitroxides inhibited the chlorinating activity of MPO in vitro with similar IC50 values (between 1.5 and 1.8μM). In vivo, the attenuation of carrageenan-induced inflammation showed some correlation with the lipophilicity of the nitroxide at early time points but the differences in the effects were small (200-fold). No inhibition of MPO activity in vivo was evident because the levels of MPO activity in rat paws correlated with the levels of MPO protein. Likewise, paw edema, levels of nitrated and oxidized proteins, and levels of plasma exudation correlated with the levels of MPO protein in the paws of the animals that were untreated or treated with the nitroxides. The effects of the nitroxides in vivo were compared with those of 4-aminobenzoic hydrazide and of colchicine. Taken together, the results indicate that nitroxides attenuate carrageenan-induced inflammation mainly by reducing neutrophil migration and the resulting MPO-mediated damage. Accordingly, tempol was shown to inhibit rat neutrophil migration in vitro.

In this report we describe the ultrasound-accelerated synthesis of new naphthoquinone derivatives 6a-f and 7a-c, which possess an aminocarbohydrate chain at the C-2 position of the quinone ring. This novel type of 1,4-naphthoquinone derivative has been synthesized under mild conditions by the reaction of 1,4-naphthoquinone (8a) or methoxylapachol (8b) with different aminocarbohydrates 9a-d. Characterization of all substances was confirmed by one- and two-dimensional nuclear magnetic resonance (NMR) techniques (¹H, 13C-APT, cosy-¹H vs. ¹H and HETCOR ¹J CH) and by high-resolution electrospray ionization mass spectrometry (HR ESI MS). Neste trabalho nós descrevemos o uso do ultrassom na síntese de novas naftoquinonas, 6a-f e 7a-c, contendo na posição 2 do anel quinonoídico substituintes do tipo aminocarboidratos. Estas substâncias foram preparadas, em condições brandas, através da reação da 1,4-naftoquinona (8a) ou do metoxi-lapachol (8b) com diferentes aminocarboidratos 9a-d. As estruturas das substâncias foram confirmadas através das técnicas de RMN de ¹H e de 13C-APT, uni- e bi-dimensionais (COSY-¹H vs. ¹H e HETCOR ¹J CH), e por espectrometria de massas de alta resolução com ionização por electrospray (ESI MS).

The current treatment used against envenomation by Lachesis muta venom still presents several side effects. This paper describes the synthesis, pharmacological and theoretical evaluations of new 1-arylsulfonylamino-5-methyl-1 H -[1,2,3]-triazole-4-carboxylic acid ethyl esters ( 8a – f) tested against the hemolytic profile of the L. muta snake venom. Their structures were elucidated by one- and two-dimensional NMR techniques ( 1 H, APT, HETCOR 1 J CH and n J CH , n = 2, 3) and high-resolution electrospray ionization mass spectrometry. The series of triazole derivatives significantly neutralized the hemolysis induced by L. muta crude venom presenting a dose-dependent inhibitory profile (IC 50 = 30−83 μM) with 1-(4′-chlorophenylsulfonylamino)-5-methyl-1 H -[1,2,3]-triazole-4-carboxylic acid ethyl ester (8e) being the most potent compound. The theoretical evaluation revealed the correlation of the antiophidian profile with the coefficient distribution and density map of the Highest Occupied Molecular Orbitals (HOMO) of these molecules. The elucidation of this new series may help on designing new and more efficient antiophidian molecules.

This paper describes the antiviral evaluation of new N-amino-1,2,3-triazole derivatives, 1-(substituted-phenylamino)-5-methyl-1H-[1,2,3]-triazole-4-carboxylic acid ethyl esters, 3 and 1-(4-substituted-phenylamino)-5-methyl-1H-[1,2,3]-triazole-4-carboxylic acid hydrazides, 4, on Cantagalo virus replication. 1-(4-Fluoro-phenylamino)-5-methyl-1H-[1,2,3]-triazole-4-carboxylic acid hydrazide, 4e, exhibited a significant antiviral effect. Characterization of all compounds was confirmed by IR, (1)H and (13)C spectroscopies and elemental analysis. In addition, molecular structure of 4e was also reported.

Structural analysis reveals the presence of supramolecular chains in a series of eight N-arylamino 1,2,3-triazole esters, which differ only in the nature of the substituent (Y) of the terminal aryl ring. In each of 1 (Y = 4-H), 3 (4-Cl), 4 (4-Br), 5 (4-I) and 6 (4-OMe), the chains are sustained by N–H⋯N hydrogen bonding. In 2 (Y = 4-F) and 8 (Y = 2,5-Cl2), the chains are mediated by alternating N–H⋯N and N–H⋯O hydrogen bonding, whereas in 7 (Y = 4-NO2) the chain is sustained by N–H⋯O hydrogen bonding only. While the differences in the adopted supramolecular motifs are qualitatively correlated with the electronegativity of the Y substituents, no quantitative correlations could be made with the electronic structures of the theoretical gas-phase molecules. Two distinct patterns of crystal packing are observed, with the first of these being based on the inter-digitation of layers, comprised of supramolecular chains and connections of the type C–X⋯π(aryl) between them for 3–5 and 8; only weak off-set edge-to-edge π⋯π interactions were noted in the case of 1. A common feature of the zigzag chains in these crystal structures was a syn-disposition of successive aryl rings along the axis of propagation. The remaining structures adopted three-dimensional architectures where the Y substituents of the anti-disposed aryl rings participated in F⋯H (2) or C–H⋯O (6 and 7) interactions. A detailed analysis of the Hirshfeld surfaces and fingerprint plots for 1–8 enabled a comparison of the intermolecular interactions involved in constructing the disparate supramolecular architectures. In the structures featuring N–H⋯N hydrogen bonding leading to the supramolecular chain, the maximum contribution to the overall crystal packing was less than 20%. This increased to over 25% in the case where there was exclusive N–H⋯O hydrogen bonding in the chain.

The presence of localised C–X⋯π [or C–X⋯π(CC)] interactions are shown to be pivotal in the crystal structures of (5-methyl-1-(4-X-arylamino)-1H-1,2,3-triazol-4-yl)methanol derivatives, X = H (1), F (2) and Cl (3). In the absence of halide (1), molecules aggregate into supramolecular chains via alternating ten-membered {⋯HOC2N}2 and 14-membered {⋯HN2C3O}2 synthons. Molecules assemble into a three-dimensional architecture via edge-to-face C–H⋯π(arene) interactions occurring between the phenyl rings. In the presence of halide (i.e. F (2) and Cl (3) in the 4-position of the phenyl ring), two-dimensional arrays are formed by interconnected ten-membered {⋯HOC2N}2 (as seen in 1) and 24-membered {⋯HO⋯NC2OH⋯N4H}2 hydrogen bonded synthons. The latter arrangement allows for the close approach of halide to the 1,2,3-triazole ring and the formation of C–X⋯π interactions which appear to be particularly significant in the case of Cl (3), as evidenced by systematic changes (i.e. elongation) in the geometric parameters within the five-membered ring. In this series of structures, the presence of C–X⋯π interactions is shown to moderate the supramolecular aggregation based on conventional hydrogen bonding.

A new one-dimensional copper(II) complex with formula [Cu(hfac)(2)(N(3)TEMPO)](n) (hfac = hexafluoroacetylacetonate and N(3)TEMPO = 4-azido-2,2,6,6-tetramethylpiperidine-1-oxyl) has been synthesized and investigated by X-ray crystallography, magnetometry and multifrequency single crystal EPR. The system crystallizes in the P1 space group with two non equivalent copper(II) ions in the unit cell, the two nitroxide radicals being coordinated to Cu(1) in axial positions. The copper(II) ions are bridged by N(3)TEMPO radicals resulting in a zig-zag chain structure. The magnetic susceptibility data were at first satisfactorily modeled assuming an alternating spin chain along the monodimensional covalent skeleton, with a ferromagnetic interaction between Cu(1) and the nitroxide moieties and a weaker antiferromagnetic interaction between these and Cu(2) (J(1) = -13.8 cm(-1), J(2) = +2.4 cm(-1)). However, single crystal EPR studies performed at the X- and W-band clearly demonstrate that the observed magnetic monodimensional character of the complex is actually due to the intermolecular contacts involving N(3)TEMPO ligands. This prompted us to fit the magnetic data using a consistent model, pointing out the fundamental role of single crystal EPR data in defining a correct model to describe the magnetic properties of molecular low dimensional systems.

Tuberculosis treatment remains a challenge that requires new antitubercular agents due to the emergence of multidrug-resistant Mycobacterium strains. This paper describes the synthesis, the antitubercular activity and the theoretical analysis of N-substituted-phenylamino-5-methyl-1 H -1,2,3-triazole-4-carbohydrazides ( 8a–b , 8e–f , 8i–j and 8n–o) and new analogues ( 8c–d , 8g–h , 8l–m and 8p–q) . These derivatives were synthesized in good yields and some of them showed a promising antitubercular profile. Interestingly the N-acylhydrazone ( NAH ) 8n was the most potent against the Mycobacterium tuberculosis H37Rv strain (MIC = 2.5 μg/mL) similar to or better than the current drugs on the market. The theoretical structure–activity relationship study suggested that the presence of the furyl ring and the electronegative group (NO 2 ) as well as low lipophilicity and small volume group at R position are important structural features for the antitubercular profile of these molecules. NMR spectra, IR spectra and elemental analyses of these substances are reported.

In this work, a new series of arysulfonylhydrazine-1H-1,2,3-triazole derivatives were synthesized, and their ability to inhibit the in vitro replication of HSV-1 was evaluated. Among the 1,2,3-triazole derivatives, 1-[(5″-methyl-1″-(4‴-fluorophenylamino)-1H-1,2,3-triazol-4″-yl)carbonyl]-2-(4'-methylphenylsulfonyl)hydrazine and 1-[(5'-methyl-1'-(2″,5″-dichlorophenylamino)-1H-1,2,3-triazol-4'-yl)carbonyl]-2-(phenylsulfonyl)hydrazine, with IC(50) values of 1.30 and 1.26 μM, respectively, displayed potent activity against HSV-1. Because these compounds have low cytotoxicity, their selectivity indices are high. Under the assay conditions, they have better performance than does the reference compound acyclovir. The structures of all of the compounds were confirmed by one- and two-dimensional NMR techniques ((1)H, (13)C-APT, COSY-(1)H×(1)H and HETCOR (1)J(CH)) and by elemental analysis.