RESUMO

The need for new drugs to treat human infections is a global health concern. Diseases like tuberculosis, trypanosomiasis, amoebiasis, and AIDS remain significant problems, especially in developing countries like Mexico. Despite existing treatments, issues such as resistance and adverse effects drive the search for new alternatives. Herein, we introduce the NUATEI research consortium, made up of experts from the Institute of Biomedical Research at UNAM, who identify and obtain natural and synthetic compounds and test their effects against human pathogens using in vitro and in vivo models. The consortium has evaluated hundreds of natural extracts and compounds against the pathogens causing tuberculosis, trypanosomiasis, amoebiasis, and AIDS, rendering promising results, including a patent with potential for preclinical studies. This paper presents the rationale behind the formation of this consortium, as well as its objectives and strategies, emphasizing the importance of natural and synthetic products as sources of antimicrobial compounds and the relevance of the diseases studied. Finally, we briefly describe the methods of the evaluation of the compounds in each biological model and the main achievements. The potential of the consortium to screen numerous compounds and identify new therapeutic agents is highlighted, demonstrating its significant contribution to addressing these infectious diseases.

RESUMO

The synthesis, crystallization and characterization of a tri-fluoro-methane-sulfonate salt of 5,10,15,20-tetra-kis-(1-benzyl-pyridin-1-ium-4-yl)-21H,23H-por-phy-rin, C68H54N8 4+·4CF3SO3 -·4H2O, 1·OTf, are reported in this work. The reaction between 5,10,15,20-tetra-kis-(pyridin-4-yl)-21H,23H-porphyrin and benzyl bromide in the presence of 0.1 equiv. of Ca(OH)2 in CH3CN under reflux with an N2 atmosphere and subsequent treatment with silver tri-fluoro-methane-sulfonate (AgOTf) salt produced a red-brown solution. This reaction mixture was filtered and the solvent was allowed to evaporate at room temperature for 3 d to give 1·OTf. Crystal structure determination by single-crystal X-ray diffraction (SCXD) revealed that 1·OTf crystallizes in the space group P21/c. The asymmetric unit contains half a porphyrin mol-ecule, two tri-fluoro-methane-sulfonate anions and two water mol-ecules of crystallization. The macrocycle of tetra-pyrrole moieties is planar and unexpectedly it has coordinated CaII ions in occupational disorder. This CaII ion has only 10% occupancy (C72H61.80Ca0.10F12N8O16S4). The pyridinium rings bonded to methyl-ene groups from porphyrin are located in two different arrangements in almost orthogonal positions between the plane formed by the porphyrin and the pyridinium rings. The crystal structure features cation⋯π inter-actions between the CaII atom and the π-system of the phenyl ring of neighboring mol-ecules. Both tri-fluoro-methane-sulfonate anions are found at the periphery of 1, forming hydrogen bonds with water mol-ecules.

RESUMO

Selective recognition of fructosyl amino acids in water by arylboronic acid-based receptors is a central field of modern supramolecular chemistry that impacts biological and medicinal chemistry. Fructosyl valine (FV) and fructosyl glycyl histidine (FGH) occur as N-terminal moieties of human glycated hemoglobin; therefore, the molecular design of biomimetic receptors is an attractive, but very challenging goal. Herein, we report three novel cationic Zn-terpyridine complexes bearing a fluorescent N-quinolinium nucleus covalently linked to three different isomers of strongly acidified phenylboronic acids (ortho-, 2Zn; meta-, 3Zn and para-, 4Zn) for the optical recognition of FV, FGH and comparative analytes (D-fructose, Gly, Val and His) in pure water at physiological pH. The complexes were designed to act as fluorescent receptors using a cooperative action of boric acid and a metal chelate. Complex 3Zn was found to display the most acidic -B(OH)2 group (pKa = 6.98) and exceptionally tight affinity for FV (K = 1.43 × 105 M-1) with a strong quenching analytical response in the micromolar concentration range. The addition of fructose and the other amino acids only induced moderate optical changes. On the basis of several spectroscopic tools (1H, 11B NMR, UV-Vis, and fluorescence titrations), ESI mass spectrometry, X-ray crystal structure, and DFT calculations, the interaction mode between 3Zn and FV is proposed in a 1 : 1 model through a cooperative two-point recognition involving a sp3 boronate-diol esterification with simultaneous coordination bonding of the carboxylate group of Val to the Zn atom. Fluorescence quenching is attributed to a static complexation photoinduced electron transfer mechanism as evidenced by lifetime experiments. The addition of FGH to 3Zn notably enhanced its emission intensity with micromolar affinity, but with a lower apparent binding constant than that observed for FV. FGH interacts with 3Zn through boronate-diol complexation and coordination of the imidazole ring of His. DFT-optimized structures of complexes 3Zn-FV and 3Zn-FGH show a picture of binding which shows that the Zn-complex has a suitable (B⋯Zn) distance to the two-point recognition with these analytes. Molecular recognition of fructosyl amino acids by transition-metal-based receptors has not been explored until now.

Assuntos

Ácidos Borônicos , Complexos de Coordenação , Corantes Fluorescentes , Piridinas , Água , Zinco , Zinco/química , Ácidos Borônicos/química , Complexos de Coordenação/química , Complexos de Coordenação/síntese química , Piridinas/química , Água/química , Corantes Fluorescentes/química , Corantes Fluorescentes/síntese química , Valina/química , Estrutura Molecular , Histidina/química

RESUMO

Raphanus sativus L. cv. Sango, commonly known as red radish, is widely consumed around the world as a vegetable, but its benefit in pain relief is not sufficiently investigated. This study aimed to evaluate the antinociceptive effects of R. sativus and a possible mechanism of action. An aqueous extract of R. sativus sprouts (AERSS) was investigated by parenteral (10, 30, and 100 mg kg-1, i.p.) and enteral (500 mg kg-1, p.o.) administration in the neurogenic and inflammatory phases of the formalin test, where gastric damage was also evaluated as a possible adverse effect. Ketorolac (5 mg kg-1, i.p.) was used as the reference drug. Endogenous opioid and 5-HT1A serotonin receptors, as well as the cAMP/NO-cGMP pathways, were explored in the study of a possible mechanism of action by using their corresponding antagonists: naloxone, 1 mg kg-1, i.p., WAY100635, 1 mg kg-1, i.p., and enzymatic activators or inhibitors, respectively. Sulforaphane (SFN), a known bioactive metabolite, was analyzed using electroencephalography (EEG) to evidence its central involvement. A significant and dose-dependent antinociceptive activity was observed with the AERSS resembling the antinociceptive effect of the reference drug, with an equivalent significant response with a dose of 500 mg kg-1, p.o. without causing gastric damage. The participation of the endogenous opioid and 5-HT1A serotonin receptors at central and peripheral levels was also observed, with a differential participation of cAMP/NO-cGMP. SFN as one metabolite produced significant changes in the EEG analysis, reinforcing its effects on the CNS. Our preclinical evidence supports the benefits of consuming Raphanus sativus cv. Sango sprouts for pain relief.

Assuntos

Analgésicos , Isotiocianatos , Extratos Vegetais , Raphanus , Transdução de Sinais , Animais , Humanos , Masculino , Camundongos , Analgésicos/farmacologia , AMP Cíclico/metabolismo , GMP Cíclico/metabolismo , Isotiocianatos/farmacologia , Dor/tratamento farmacológico , Extratos Vegetais/farmacologia , Raphanus/química , Receptor 5-HT1A de Serotonina/metabolismo , Receptores Opioides/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sulfóxidos/farmacologia

RESUMO

Organophosphorus pesticides (OPPs) such as parathion have extensive uses in agriculture and household applications. Chronic exposure to these pesticides can cause severe health and environmental issues. Therefore, a current ecological concern is associated with accumulating these noxious OPPs in food and water sources. In this work, a new Tb3+-doped Zn-LMOF (Zn-LMOF= (3D) {[Zn3(1,4 benzenedicarboxylate)3(EtOH)2]·(EtOH)0.6}∞) was synthesized by a solvent-free reaction between the Zn-LMOF and the salt TbCl3·6H2O using a high-speed ball milling. The Tb@Zn-LMOF was thoroughly characterized by multiple spectroscopic tools, including Scanning Electron Microscopy with Energy-Dispersive X-ray Spectroscopy, and studied in-depth as a luminescent sensor for a series of pesticides (parathion, malathion, methalaxil, carbofuran, iprodione, captan and glyphosate) in aqueous methanol. The Tb@Zn-LMOF is a long-lived green-emitting compound with luminescence originated by an efficient antenna effect from the excited energy levels of Zn-LMOF toward the 5D state of Tb3+ ions, as it is displayed by its strong emission bands at 488, 545, 585, and 620 nm and a lifetime of 1.01 ms upon excitation at 290 nm. Additions of pesticides to a neutral methanolic dispersion of Tb@Zn-LMOF modified its green emission intensity with a pronounced selectivity toward parathion within the micromolar concentration range. The detection limit for parathion was calculated to be 3.04 ± 0.2 µM for Tb@Zn-LMOF. Based on 31P NMR and mass spectrometry studies, it is attributed to the release of lanthanide ions from Tb@Zn-LMOF with the simultaneous formation of a Tb3+-parathion complex.

Assuntos

Estruturas Metalorgânicas , Paration , Praguicidas , Estruturas Metalorgânicas/química , Luminescência , Praguicidas/análise , Compostos Organofosforados , Íons/análise , Zinco

RESUMO

Coamorphous salt in a 1:1 ratio prepared by ball milling from Fluvastatin sodium (FLV) and Pioglitazone hydrochloride (PGZ·HCl) can be selectively formed by neat grinding (NG). Furthermore, the salt-cocrystal continuum was preferably formed by employing liquid-assisted grinding (LAG) using ethanol (EtOH). Attempts to prepare the coamorphous salt starting from the salt-cocrystal continuum by NG were unsuccessful. Interestingly, through ball milling by NG or LAG, a great diversity of solid forms (PGZ·HCl-FLV 1:1) could be accessed: NG and hexane (coamorphous); ethyl acetate (physical mixture); EtOH (salt-cocrystal continuum); and water (which presents two Tg, indicating immiscibility of the components). An exploration was performed at different drug-to-drug ratios by NG. By differential scanning calorimetry (DSC), the presence of two endothermic events was observed in this screening: incongruous melting point (solidus) and excess of one of the components (liquidus), except in the 1:1 solid form. From these results, eutectic behavior was observed. Through the construction of a binary phase diagram, it was determined that the 1:1 molar ratio gives rise to the formation of the most stable coamorphous composition. Dissolution profile studies of these solid forms were carried out, specifically on pure FLV and the solid forms of PGZ⋅HCl-FLV (1:2; 1:4; and 1:6), together with the coamorphous 1:1 salt. By itself, pure FLV presented the highest Kint (13.6270 ± 0.8127 mg/cm2⋅min). On the other hand, the coamorphous 1:1 showed a very low Kint (0.0220 ± 0.0014 mg/cm2·min), indicating very fast recrystallization by the FLV, which avoids observing a sudden release of this drug in the solution. This same behavior was observed in the eutectic composition 1:2. In the other solid forms, the value of Kint increases along with the %w of FLV. From the mechanochemical point of view, ball milling by NG or LAG became an important synthetic tool since it allows obtaining a great variety of solid forms to explore the solid-state reactivity of the drug-drug solid-form PGZ HCl-FLV.

RESUMO

Selective anion sensing by luminescent chemosensors capable of operating in aqueous conditions is a central field of modern supramolecular chemistry that impacts analytical and biological chemistry. A cationic cyclometalated [Pt(N^C^N)NCCH3]OTf complex, 1 [N^C^N = 1,3-bis(1-(p-tolyl)-benzimidazol-2'-yl)benzene, OTf = triflate], was prepared, structurally described by single-crystal X-ray diffraction and studied in-depth as a luminescent chemosensor for anions in aqueous phase and solid state. A series of related neutral [Pt(N^C^N)X] complexes (X = Cl, 2; CN, 3 and I, 4) were formed readily upon treatment of 1 with the respective NaX salt in aqueous media and were described structurally by X-ray diffraction. Complex 1 is hydrostable with phosphorescent green emission originated by intraligand transitions, and [dyz(Pt) → π*(N^C^N)] charge transfer transitions, as evidenced by TD-DFT calculations and lifetime. Additions of halides, pseudohalides, oxyanions, and dicarboxylates to a neutral aqueous solution of 1 modified its green emission intensity with a pronounced affinity (K = 1.5 × 105 M-1) and turn-on signal toward Cl- within the micromolar concentration range. Pt complex 1 is two orders of magnitude more selective for Cl- than the other halides, CN- and basic oxyanions. Such Cl- affinity for a metal-based chemosensor in aqueous media is still rare. On the basis of X-ray crystallographic analysis and multiple spectroscopic tools (NMR, UV-vis, luminescence, MS, lifetimes) the origin of this selectivity hinges on the cooperative three-point recognition involving one coordination bond (Pt-Cl) and two convergent short C-H···Cl- contacts. This strong affinity and efficient optical response can be utilized in quantitative Cl- sensing in real samples and solid-liquid extractions. Additionally, chloro-Pt complex, 2 may be relevant to bioimaging as a marker for cell nuclei, as revealed by its emission within living cells and intracellular distribution by confocal microscopic studies. These results demonstrate the usefulness of the new water-stable luminescent Pt-N^C^N complexes as effective analytical tools in anion sensing and extraction agents.

RESUMO

Three new diboronic acid-substituted bisquinolinium salts were synthesized, structurally described by single-crystal X-ray diffraction, and studied in-depth as fluorescent receptors for six monosaccharides and two open-chain polyols in water at physiological pH. The dicationic pyridine-2,6-dicarboxamide-based receptors contain two N-quinolinium rings as the fluorescent units covalently linked to three different isomers of phenylboronic acid (ortho, 2; meta, 3; and para, 4) as chelating binding sites for polyols. Additions of glucose/fructose in the micromolar concentration range to receptors 2 and 3 induce significant fluorescence changes, but in the presence of arabinose, galactose, mannose, and xylose, only modest optical changes are observed. This optical change is attributed to a static photoinduced electron transfer mechanism. The meta-diboronic receptor 3 exhibited a high affinity/selectivity toward glucose (K = 3800 M-1) over other monosaccharides including common interfering species such as fructose and mannitol. Based on multiple spectroscopic tools, electrospray ionization high-resolution mass spectrometry, crystal structures, and density functional theory calculations, the binding mode between 3 and glucose is proposed as a 1:1 complex with the glucofuranose form involving a cooperative chelating diboronate binding. These results demonstrate the usefulness of a new set of cationic fluorescent diboronic acid receptors with a strong ability for optical recognition of glucose in the sub-millimolar concentration range.

RESUMO

Ball-milling using neat grinding (NG) or liquid-assisted grinding (LAG) by varying the polarity of the solvents allowed access to various drug-drug solid forms of pioglitazone hydrochloride (PGZ·HCl) and rosuvastatin calcium (RSV). Using NG, the coamorphous form was formed from the reaction of pioglitazone hydrochloride (PGZ·HCl) and rosuvastatin calcium (RSV) in a 2:1 molar ratio. The formation of the expected coamorphous salt could not be corroborated by FT-IR, but DSC data showed that it was indeed a single-phase amorphous mixture. By varying the molar ratios of the reactants, either keeping PGZ·HCl constant and varying RSV or vice versa, another coamorphous form was obtained when a 1:1 molar ratio was employed. In the case of the other outcomes, it was observed that they were a mixture of solid forms coexisting simultaneously with the coamorphous forms (1:1 or 2:1) together with the drug that was in excess. When RSV was in excess, it was in an amorphous form. In the case of PGZ·HCl, it was found in a semicrystalline form. The intrinsic dissolution rates (IDRs) of the solid forms of PGZ·HCl-RSV in stoichiometric ratios (1:1, 2:1, 1:4, 6:1, and 1:10) were evaluated. Interestingly, a synchronized release of both drugs in the dissolution medium was observed. In the case of the release of RSV, there were no improvements in the dissolution profiles, because the acidic media caused the formation of degradation products, limiting any probable modification in the dissolution processes. However, the coamorphous 2:1 form exhibited an improvement of 1.03 times with respect to pure PGZ·HCl. It is proposed that the modification of the dissolution process of the coamorphous 2:1 form was limited by changes in the pH of the media as RSV consumes protons from the media due to degradation processes.

RESUMO

The mechanochemical synthesis of drug-drug solid forms containing metformin hydrochloride (MET·HCl) and thiazide diuretics hydrochlorothiazide (HTZ) or chlorothiazide (CTZ) is reported. Characterization of these new systems indicates formation of binary eutectic conglomerates, i.e., drug-drug eutectic solids (DDESs). Further analysis by construction of binary diagrams (DSC screening) exhibited the characteristic V-shaped form indicating formation of DDESs in both cases. These new DDESs were further characterized by different techniques, including thermal analysis (DSC), solid state NMR spectroscopy (SSNMR), powder X-ray diffraction (PXRD) and scanning electron microscopy-energy dispersive X-ray spectroscopy analysis (SEM-EDS). In addition, intrinsic dissolution rate experiments and solubility assays were performed. In the case of MET·HCl-HTZ (χMET·HCl = 0.66), we observed a slight enhancement in the dissolution properties compared with pure HTZ (1.21-fold). The same analysis for the solid forms of MET·HCl-CTZ (χMET·HCl = 0.33 and 0.5) showed an enhancement in the dissolved amount of CTZ accompanied by a slight improvement in solubility. From these dissolution profiles and saturation solubility studies and by comparing the thermodynamic parameters (ΔHfus and ΔSfus) of the pure drugs with these new solid forms, it can be observed that there was a limited modification in these properties, not modifying the free energy of the solution (ΔG) and thus not allowing an improvement in the dissolution and solubility properties of these solid forms.

RESUMO

Optical sensors with high sensitivity and selectivity, as important analytical tools for chemical and environmental research, can be realized by straightforward synthesis of luminescent one-, two- and three-dimensional Zn(ii) and Cd(ii) crystalline coordination arrays (CPs and MOFs). In these materials with emission centers typically based on charge transfer and intraligand emissions, the quantitative detection of specific analytes, as pesticides or anions, is probed by monitoring real-time changes in their photoluminescence and color emission properties. Pesticides/herbicides have extensive uses in agriculture and household applications. Also, a large amount of metal salts of cyanide is widely used in several industrial processes such as mining and plastic manufacturing. Acute or chronic exposure to these compounds can produce high levels of toxicity in humans, animals and plants. Due to environmental concerns associated with the accumulation of these noxious species in food products and water supplies, there is an urgent and growing need to develop direct, fast, accurate and low-cost sensing methodologies. In this critical frontier, we discuss the effective strategies, chemical stability, luminescence properties, sensitivity and selectivity of recently developed hybrid Zn(ii)/Cd(ii)-organic materials with analytical applications in the direct sensing of pesticides, herbicides and cyanide ions in the aqueous phase and organic solvents.

Assuntos

Cádmio/química , Complexos de Coordenação/química , Corantes Fluorescentes/química , Herbicidas/análise , Praguicidas/análise , Zinco/química , Complexos de Coordenação/síntese química , Corantes Fluorescentes/síntese química , Processos Fotoquímicos

RESUMO

Biological catecholamines such as l-DOPA and dopamine play vital physiological roles in the brain and are chemical indicators of human diseases. A new range of fluorescent Zn(ii)-terpyridine complexes are described and studied in-depth as chemosensors for catecholamine-based neurotransmitters and nucleosides in pure water. The new Zn-terpyridine-based chemosensors contain a cationic N-isoquinolinium nucleus as the optical indicator covalently linked to three different isomers of strongly acidified phenylboronic acids (ortho-, 2.Zn; meta-, 3.Zn and para-, 4.Zn, substituted derivatives) as catechol binding sites. The addition of l-DOPA, dopamine, epinephrine, l-tyrosine and nucleosides to Zn(ii)-boronic acid chemosensors at physiological pH quenches their blue emission with a pronounced selectivity and an unprecedented high affinity towards l-DOPA (log K = 6.01). This efficient response by l-DOPA was also observed in the presence of coexisting species in blood plasma and urine with a detection limit of 3.0 µmol L-1. A photoinduced electron transfer quenching mechanism with simultaneous chemosensor-l-DOPA complexation in both the excited and ground states is proposed. The fluorescence experimental observations show that the 2.Zn·eosin-Y adduct can be used as a selective naked-eye chemosensing ensemble for l-DOPA with a fast turn-on fluorescent response and color change from blue to green under UV light at the micromolar level. On the basis of multiple spectroscopic techniques (1H, 11B NMR, UV-Vis, and fluorescence), MS-ESI experiments, crystal structures, and DFT calculations, the binding mode between Zn(ii)-chemosensors and l-DOPA is proposed in a 1 : 1 model through a cooperative two-point recognition involving the reversible esterification of the boronic acid moiety with the aromatic diol fragment of l-DOPA together with the coordination of the carboxylate anion to the Zn(ii) atom with strong electrostatic contribution.

Assuntos

Ácidos Borônicos/química , Corantes Fluorescentes/química , Neurotransmissores/análise , Piridinas/química , Zinco/química , Cristalografia por Raios X , Corantes Fluorescentes/síntese química , Modelos Moleculares , Estrutura Molecular

RESUMO

Preliminary analysis of the mass spectrometric (MS) and NMR spectroscopic data of the primary fractions from the biologically active extract of Salvia decora revealed spectra that are characteristic for neo-clerodane-type diterpenoids. MS-guided isolation of the bioactive fractions led to the isolation of three new chemical entities, including two hydroxy-neo-clerodanes (1 and 2) and one acylated 5,10-seco-neo-clerodane (3), along with three known diterpenoids (4-6), ursolic acid (7), and eupatorin (8). The structures of the new compounds were established by analysis of the 1D and 2D NMR and MS data, whereas their absolute configuration was deduced using a combination of experimental and theoretical ECD data and confirmed by X-ray crystallography (1 and 4). Furthermore, compounds 1, 3, 4, and 6-8 were evaluated as hPTP1B1-400 (human protein tyrosine phosphatase) inhibitors, where 7 showed the best activity, with an IC50 value in the lower µM range. Additionally, compound 7 was evaluated as an α-glucosidase inhibitor. The affinity constant of the 7-hPTP1B1-400 complex was determined by quenching fluorescence experiments (ka = 1.3 × 104 M-1), while the stoichiometry ratio (1:1 protein-ligand) was determined by a continuous variation method.

Assuntos

Diterpenos Clerodânicos/isolamento & purificação , Salvia/química , Cristalografia por Raios X , Diterpenos Clerodânicos/química , Estrutura Molecular , Análise Espectral/métodos

RESUMO

Four coordination polymers have been synthesized using self-assembly solution reactions under ambient conditions, reacting Cd(ii) ions with 1,4-cyclohexanedicarboxylic acid in the presence of different 2,2'-bipyridine co-ligands: {[Cd(H2O)(e,a-cis-1,4-chdc)(2,2'-bpy)]·H2O}n (1); [Cd2(H2O)2(e,a-cis-1,4-chdc)2(4,4'-dmb)2]n (2); {[Cd(e,a-cis-1,4-chdc)(5,5'-dmb)]·H2O·CH3OH}n (3) and {[Cd(e,e-trans-1,4-chdc)(4,4'-dtbb)]·CH3OH}n (4), where 1,4-chdc = 1,4-cyclohexanedicarboxylato, 2,2'-bpy = 2,2'-bipyridine, 4,4'-dmb = 4,4'-dimethyl-2,2'-bipyridine, 5,5'-dmb = 5,5'-dimethyl-2,2'-bipyridine and 4,4'-dtbb = 4,4'-di-tert-butyl-2,2'-bipyridine. Crystallographic studies show that compound 1 has a 1D structure propagating along the crystallographic b-axis; the Cd ion in 1 is six-coordinated with a distorted-octahedral coordination sphere. Compound 2 has two crystallographic different Cd ions and both are six-coordinated with a distorted-octahedral coordination sphere. Compound 3 exhibits a seven-coordinated Cd ion having a distinctive distorted-monocapped trigonal prismatic geometry. In compound 4, the Cd ion is also seven-coordinated in a distorted monocapped octahedral geometry. Compounds 2, 3 and 4 possess rhombic-shaped dinuclear units (Cd2O2) as nodes to generate larger cycles made up of four dinuclear units, a Cd4 motif, bridged by four 1,4-chdc ligands, accomplishing, thus, 2D structures. Remarkably, in compound 4 the 1,4-chdc ligand conformation changes to the equatorial, equatorial trans, unlike the other compounds where the bridging ligand conformation is the more typical equatorial, axial cis. The solid state luminescence properties of 1-4 were investigated; polymers 3 and 4 exhibited a strong blue emission (λem = 410-414 nm) compared to 1 and 2; structure-related photoluminescence is attributed to the degree of hydration of the compounds. Furthermore, Cd-polymer 3 suspended in acetone allows the fluorescence selective sensing of acetonitrile over common organic solvents such as alcohols and DMF, based on turn-on fluorescence intensity with a limit of 53 µmol L-1.

RESUMO

CONTEXT: Lippia species (Verbenaceae) are widely used in Latin America and Africa as folk medicine for their tranquilizing properties. OBJECTIVE: To evaluate the anxiolytic-like effects and safety of Lippia graveolens Kunth. by exploring its aqueous and organic leaf extracts and identifying the responsible chemical constituents. MATERIAL AND METHODS: Aqueous and organic extracts (hexane, ethyl acetate and methanol) were pharmacologically evaluated at several doses. Chemical constituents were identified using MS, NMR and GC-MS analysis. The isolated compounds (3 mg/kg, i.p.), extracts (1, 3, 10 and 30 mg/kg, i.p.), and the reference drug diazepam (0.1 mg/kg, i.p.) were assessed in CD-1 mice using experimental behavioural models: open-field, cylinder, hole-board, plus-maze and sodium pentobarbital-induced hypnosis, as well as their acute toxicity (LD50). RESULTS: After administration of the extracts and bioactive compounds, a significant anxiolytic-like response from 1 mg/kg, i.p. was observed, resembling the effect of diazepam. Major presence of thymol (33.40%) was observed in the hexane extract; whereas for the first time in this species a p-cymene + thymol mixture (9.78%), naringenin (0.18%) and cirsimaritin (1.16%) were obtained as bioactive constituents of the ethyl acetate crude extract. Acute toxicity was calculated to be LD50 = 1000 mg/kg for the crude hexane extract, lower in comparison to the other extracts analyzed (LD50 > 2000 mg/kg). DISCUSSION AND CONCLUSION: Our results suggest that L. graveolens exerts anxiolytic-like activity involving many kinds of constituents, mainly of the terpenoid and flavonoid nature. These results reinforce the potential use of this species in the therapy of anxiety.

Assuntos

Ansiolíticos/farmacologia , Ansiedade/prevenção & controle , Lippia/química , Compostos Fitoquímicos/farmacologia , Extratos Vegetais/farmacologia , Animais , Ansiolíticos/isolamento & purificação , Ansiolíticos/toxicidade , Ansiedade/psicologia , Comportamento Animal/efeitos dos fármacos , Diazepam/farmacologia , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Cromatografia Gasosa-Espectrometria de Massas , Dose Letal Mediana , Espectroscopia de Ressonância Magnética , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/toxicidade , Fitoterapia , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/toxicidade , Folhas de Planta/química , Plantas Medicinais , Sono/efeitos dos fármacos , Solventes/química

RESUMO

In the title compound, C23H18N3O3 (+)·CF3SO3 (-), the asymmetric unit contains two crystallographically independent organic cations with similar conformations. Each cation shows a moderate distortion between the planes of the amide groups and the quinolinium rings with dihedral angles of 14.90 (2) and 31.66 (2)°. The quinolinium and phenyl rings are slightly twisted with respect to each other at dihedral angles of 6.99 (4) and 8.54 (4)°. The tri-fluoro-methane-sulfonate anions are linked to the organic cations via N-H⋯O hydrogen-bonding inter-actions involving the NH amide groups. In the crystal, the organic cations are linked by weak C-H⋯O(nitro group) inter-actions into supramol-ecular chains propagating along the b-axis direction.

RESUMO

In the centrosymmetric title compound, C26H16N4O4 {systematic name: 6,13-bis-[(pyridin-4-yl)meth-yl]-6,13-di-aza-tetra-cyclo-[6.6.2.0(4,16)0(11,15)]hexa-deca-1,3,8,10,15-pantaene-5,7,12,14-tetrone}, the central ring system is essentially planar [maximum deviation = 0.0234 (8) Å] and approximately perpendicular to the terminal pyridine ring [dihedral angle = 84.38 (3)°]. The mol-ecules displays a trans conformation with the (pyridin-4-yl)methyl groups on both sides of the central naphthalene di-imide plane. In the crystal, mol-ecules are linked by π-π stacking between parallel pyridine rings [centroid-centroid distances = 3.7014 (8) and 3.8553 (8) Å] and weak C-H⋯O hydrogen bonds, forming a three-dimensional supra-molecular architecture.