Géssica A. Vasconcelos

Paper spray ionization mass spectrometry applied to forensic chemistry – drugs of abuse, inks and questioned documents

With the advent of a new family of ionization techniques, ambient mass spectrometry (or ambient MS) was introduced as a simple way of generating ions in MS. Among them, the paper spray ionization (PS-MS) technique has demonstrated to be versatile to solve numerous problems in many areas of science. In this work, the PS-MS technique in the positive ionization mode (PS(+)-MS) was applied in two subareas of forensic chemistry: drugs of abuse and documentoscopy. In the first, the PS(+)MS technique was applied to obtain the chemical profiles of illicit drugs such as blotter papers containing 25I-NBOMe, extracts and leaves of natural cannabinoids (Δ9-tetrahydrocannabinol) and synthetic cannabinoids (naphthalen-1-yl-(1-butylindol-3-yl)methanone, (JWH-073); n-(adamantan-1-yl)-1-(4-fluorobutyl)-1H-indazole-3-carboxamide (5F-AKB48); 4-methyl-1-naphthyl-1-pentylindol-3-yl-methanone (JWH-122); 2-(2-methoxyphenyl)-1-(1-pentylindol-3-yl)ethanone (JWH-250); and 4-ethylnaphthalen-1-yl-(1-pentylindol-3-yl)methanone (JWH-210)) as well as to determine the authenticity in weight-loss herbal samples. Finally, an analytical method has been developed to quantify eight illicit drugs (3,4-methylenedioxyamphetamine (MDA), 3,4-methylenedioxy-N-methylamphetamine (MDMA), 3,4-methylenedioxy-N-ethylamphetamine (MDEA), meta-chlorophenylpiperazine (m-CPP), methamphetamine (MA), cocaine, lysergic acid diethylamide (LSD), and dimethoxybromoamphetamine (DOB)) where their limit-of-detection ranged from 0.17 to 1 ppb, with linearity R2 > 0.99. The performance of the PS(+)-MS technique was also compared to other ionization sources: leaf spray mass spectrometry (LS-MS), and electrospray ionization mass spectrometry (ESI-MS). In the second part of this study, the PS(+)MS technique was successfully able to obtain the chemical profiles of different commercial blue pens. The relative intensity (RII372) of the methylene blue dye was monitored to discriminate crossings of traces, and to date questioned documents. The chemical profile of the second generation of Brazilian banknotes (R

Design, synthesis and pharmacological evaluation of new anti-inflammatory compounds.

, reais) was also explored. In general, the PS(+)-MS technique was proved to be an excellent analytical tool in forensic chemistry, acting like a “Swiss army knife”.

Pharmacological evaluation and molecular docking of new di-tert-butylphenol compound, LQFM-091, a new dual 5-LOX/COX inhibitor

Inflammatory diseases and pain are among the main problems that significantly influence the lifestyle of millions of people and existing therapies are not always effective and can cause several adverse effects. In this context, the molecular modifications or synthesis of compounds continue being the best strategies for the identification of new compounds for the treatment of pain and inflammation. The aim of this study was to evaluate the analgesic and anti-inflammatory activities of new analogues of pyrazole compounds containing subunits N-phenyl-1-H-pirazoles and 1,3,4-oxadiazole-2(3H)-thione, LQFM-146, LQFM-147 and LQFM-148. In the acetic acid-induced abdominal writhing test, treatments with LQFM-146, LQFM-147 or LQFM-148 at doses 89, 178 and 356µmol/kg p.o. reduced the abdominal writhing in a dose-dependent manner. In the formalin test, these compounds at dose 178µmol/kg p.o. reduced the licking time only in inflammatory phase of this test, suggesting an antinociceptive effect dependent of the anti-inflammatory effect. The treatment with the three compounds in intermediate dose (178µmol/kg p.o.) reduced the edema at all tested time points in the carrageenan-induced paw edema test and reduced polymorphonuclears cell migration, activity myeloperoxidase and TNF-α levels in the carrageenan-induced pleurisy test. Our date suggest that the new compounds LQFM-146, LQFM-147 and LQFM-148 possess satisfactory anti-inflammatory and antinociceptive effects that involves the reduction of pro-inflammatory cytokines and inhibition of the myeloperoxidase enzyme.

Lower rim dimerization of a calixarene through the encapsulation of sodium ions

Abstract Dual 5‐LOX/COX inhibitors are potential new dual drugs to treat inflammatory conditions. This research aimed to design, synthesis and to evaluate the anti‐inflammatory and antinociceptive effects of the new compound, which is derived from nimesulide and darbufelone lead compounds. The new dual inhibitor 5‐LOX/COX has the possible advantage of gastrointestinal safety. A voltammetric experiment was conducted to observe the drugs antioxidative effect. A formalin test, a hot plate test and carrageenan‐induced mechanical hyperalgesia were employed to evaluate the analgesic nature of LQFM‐091. To evaluate anti‐inflammatory activity, we measured edema, leukocyte count, myeloperoxidase activity and cytokines levels in carrageenan‐induced inflammation tests. We elucidated the underlying mechanisms by assessing the interaction the with COXs and LOX enzymes by colorimetric screening assay and molecular docking. The lethal dose (LD50) was estimated using 3T3 Neutral Red Uptake assay. Our results indicate that the LQFM‐091 prototype is a powerful antioxidant, as well as able to inhibit COX‐1, COX‐2 and LOX activities. LQFM091 was classified in GHS category 4 (300 < LD50 < 2000 mg/Kg). This prototype showed analgesic activity in the formalin test and decreased carrageenan‐induced mechanical hyperalgesia. Furthermore, LQFM‐091 reduced the paw edema induced by carrageenan and reduced the leukocyte count, myeloperoxidase activity, TNF‐&agr; and IL‐1&bgr; levels in the pleural exudate. Another interesting finding was the absence of gastrointestinal lesions. These data indicate that LQFM‐091 produced antinociceptive and anti‐inflammatory effects while maintaining gastrointestinal safety. Furthermore, this compound presented a safe toxicological profile. Blocked COXs and LOX enzymes are important targets for manipulating the mechanism of this compound. Graphical abstract Figure. No Caption available.

Synthesis and leishmanicidal activity of eugenol derivatives bearing 1,2,3-triazole functionalities

Here we report the tail-to-tail dimerization of tetra(carboxymethoxy)calix[4]arene in both solution and solid state phases using ESI-orbitrap UHRMS, 1H-NMR and single-crystal X-ray diffraction techniques. Three sodium ions are encapsulated into the dimeric structure which is also stabilized by hydrogen bonds between carboxyl moieties undergoing partial deprotonation.

Probing the competition between acetate and 2,2′-bipyridine ligands to bind to d-block group 12 metals

In this paper, it is described the synthesis and the evaluation of the leishmanicidal activity of twenty-six eugenol derivatives bearing 1,2,3-triazole functionalities. The evaluation of the compounds on promastigotes of Leishmania amazonensis (WHOM/BR/75/Josefa) showed that eugenol derivatives present leishmanicidal activities with varying degrees of effectiveness. The most active compound, namely 4-(3-(4-allyl-2-methoxyphenoxy)propyl)-1-(4-methylbenzyl)-1H-1,2,3-triazole (7k) (IC50 = 7.4 ± 0.8 μmol L-1), also targeted Leishmania parasites inside peritoneal macrophages (IC50 = 1.6 μmol L-1) without interfering with cell viability. The cytotoxicity of 7k against macrophage cells presented IC50 of 211.9 μmol L-1 and the selective index was equal to 132.5. Under similar conditions, compound 7k was more effective than glucantime and pentamidine, two drugs currently in the clinic. In addition, theoretical calculations showed that this compound also presents most physicochemical and pharmacokinetic properties within the ranges expected for orally available drugs. It is believed that eugenol bearing 1,2,3-triazole functionalities may represent a scaffold to be explored toward the development of new agents to treat leishmaniasis.

Prediction of Total Acid Number in Distillation Cuts of Crude Oil by ESI(−) FT‑ICR MS Coupled with Chemometric Tools

Herein, we were interested in probing the competition between 2,2′-bipyridine (2,2′-bipy) and acetate ligands in binding to Zn2+, Cd2+ and Hg2+. We have obtained eight new supramolecular architectures through tuning the proportion of these two ligands. On doubling the acetate availability compared to 2,2′-bipy, complexes with either Zn2+, Cd2+ or Hg2+ were formed with one 2,2′-bipy and two acetate ligands coordinated to the metal center. One water molecule is also coordinated to Zn2+ and Cd2+ in these two complexes, which are reported here for the first time. One 2,2′-bipy is still coordinated to the three metal ions with an acetate excess of 10-times, but another trinuclear Zn2+ complex is formed with two 2,2′-bipy and six acetate ligands (1 : 3 2,2′-bipy : acetate stoichiometry). Upon setting an equimolar ratio of the ligands, the complex [Zn(CH3CO2)(2,2′-bipy)2]+ is formed, while two 2,2′-bipy and two acetate ligands are coordinated to Cd2+, giving rise to a [Cd(CH3CO2)2(2,2′bipy)2] complex. On doubling the 2,2′-bipy availability compared to acetate, the former does not coordinate to Zn2+ and Cd2+, as observed in the acetate salt form of [Zn(2,2′-bipy)3]2+ and in [Cd(2,2′-bipy)3]2+. This last Cd2+ complex did not crystallize, revealing its unfavorable crystallization as an acetate salt form. However, under this last ligand ratio, the persistence of at least one coordinated acetate was observed in the Hg2+ complex with 2 : 1 2,2′-bipy : acetate stoichiometry. Furthermore, there is a cocrystallized 2,2′-bipy in the acetate salt form of [Hg(CH3CO2)(2,2′-bipy)2]+, which is not able to win the competition with acetate for the third coordination site to Hg2+. Even if the 2,2′-bipy amount is 10-times higher than that of acetate in the reaction batch, one acetate remains coordinated to Hg2+. Our crystal form of [Zn(CH3CO2)(2,2′-bipy)2]+ is strongly photoluminescent, with highly efficient emission centered at 356 nm (external and internal quantum yields of 14.2(1)% and 41.3(1)%), whose optical efficiency was rationalized on the basis of time-dependent DFT calculations.

Chemical characterization and pharmacological assessment of polysaccharide free, standardized cashew gum extract (Anacardium occidentale L.)

Competitive adaptive reweighted sampling-partial least squares (CARS-PLS) and negative-ion mode electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI(−) FT-ICR MS) data were adopted to assess the total acid number (TAN) of crude oil distillation cuts. Two crude oil samples and 24 derivatives with TAN ranging from 0.20 to 0.39 mg of KOH g were investigated. The multivariate calibration PLS model was built with 18 calibration samples and tested with 8 validation samples. CARS-PLS reduced the number of variables from 1610 to only 4, allowing the identification of molecular formulas that are truly related to the TAN. The root mean square error of prediction (RMSEP) obtained was 0.01 mg of KOH g, which is lower than the error when using all variables (0.03 mg of KOH g). Finally, it was observed that the N and O2 compound classes are the most important classes for providing a better correlation between ESI(−) FT-ICR mass spectra and TAN values.

Molecular docking and pharmacological/toxicological assessment of a new compound designed from celecoxib and paracetamol by molecular hybridization

ETHNOPHARMACOLOGICAL RELEVANCE The cashew gum (Anacardium occidentale L.) is used in traditional Brazilian medicine in the treatment of inflammatory conditions, asthma, diabetes, and gastrointestinal disturbances. AIM OF THE STUDY In the present study, we aimed at forming a chemical characterization and investigation of the antinociceptive and anti-inflammatory activities of the aqueous extract of cashew gum without the presence of polysaccharides in its composition (CGE). MATERIALS AND METHODS The CGE was obtained after the precipitation and removal of polysaccharides through the use of acetone. After, the acetone was removed by rotaevaporation, and the concentrated extract was lyophilized. The chemical characterization of CGE was performed by liquid chromatography mass spectrometry (LC-MS) and tandem mass spectrometry (MS/MS) analyses. Mice were used for the evaluation of the antinociceptive and anti-inflammatory activities. CGE was analyzed via the Irwin test, acetic acid-induced writhing test, formalin-induced pain test, and carrageenan-induced paw edema test. The motor activity or probable sedation was verified through the chimney, open-field, and sodium pentobarbital-induced sleep tests. We investigated if the analgesic and anti-inflammatory effects of CGE depend of reduction in PGE2 levels, were performed the carrageenan or PGE2-induced hyperalgesia tests. RESULTS The chemical characterization of CGE showed the presence of anacardic acids as the predominant phytoconstituents. The treatment with CGE (75, 150, and 300mg/kg, p.o.) inhibited the number of writhing in a dose-dependent manner. With an intermediate dose, CGE did not cause motor impairment with the chimney test or alterations in either the open-field or sodium pentobarbital-induced sleep. In the formalin-induced pain test, CGE (150mg/kg, p.o.) produced an antinociceptive effect only in the first phase of the test, suggesting anti-inflammatory activity. With the same dosage, CGE also reduced the carrageenan-induced paw edema at all hours of the test, confirming its anti-inflammatory effect. Furthermore, CGE (150mg/kg, p.o.) presented an antihyperalgic effect at all hours of the carrageenan-induced hyperalgesia test. However, this dose of CGE was not able to reduce the hyperalgesia induced by PGE2, suggesting that the anti-inflammatory effect of this extract depends on the reduction in the PGE2 levels. CONCLUSION The anacardic acids are the predominant phytoconstituents identified in the CGE. The action mechanisms of CGE suggest the reduction in the PGE2 levels. These findings support the use of cashew gum in popular medicine and demonstrate that part of its antinociceptive and anti-inflammatory effects should also be attributed to the presence of anacardic acids in its composition, independent of the presence of polysaccharides.The cashew gum (Anacardium occidentale L.) is used in Brazilian traditional medicine in the treatment of inflammatory conditions, asthma, diabetes, and gastrointestinal disturbs.The present study was aimed the chemical characterization and the investigation of the antinociceptive and anti-inflammatory activities of cashew gum aqueous extract without the presence of polysaccharides in its composition (CGE).The CGE was obtained after precipitation and removal of polysaccharides using acetone. Acetone solvent was removed from the CGE by rotaevaporation and subsequently this concentrated extract was lyophilized. The chemical characterization of CGE was performed by Liquid Chromatography Mass Spectrometry (LC-MS) and Tandem Mass Spectrometry (MS/MS) analysis. Mice were used for the evaluation of the antinociceptive and anti-inflammatory activities. CGE was analyzed in Irwin test, acetic acid-induced writhing test, formalin-induced pain test and carrageenan-induced paw edema and hyperalgesia tests. Also, the motor activity or probable sedation was verified in chimney test, open-field, and sodium pentobarbital-induced sleep tests. In the investigation of the action mechanisms of CGE, were performed the PGE2-induced hyperalgesia test to investigate the possible involvement of an inhibition of PGE2 synthesis in the analgesic and anti-inflammatory effects of CGE.The chemical characterization of CGE showed the presence of anacardic acids as predominant phytoconstituents. The treatment with CGE (75, 150 and 300mg/kg, p.o.) inhibited the number of writhing in a dose-dependent manner. In intermediate dose, CGE did not cause motor impairment in chimney test or alterations in open-field and sodium pentobarbital-induced sleep. In the formalin-induced pain test, CGE (150mg/kg, p.o.) produced antinociceptive effect only in the first phase of the test, suggesting an anti-inflammatory activity. In the same dose, CGE also reduced the carrageenan-induced paw edema at all hours of the test, confirm its anti-inflammatory effect. Furthermore, CGE (150mg/kg, p.o.) presented antihyperalgic effect in at all hours of the carrageenan-induced hyperalgesia test. However, this some dose of CGE was not able to reduce the hyperalgesia induced by PGE2, suggesting that the anti-inflammatory effect of this extract depends on the reduction in the PGE2 levels.The anacardic acids are the predominant phytoconstituents identified in the CGE, which has significant antinociceptive and anti-inflammatory effects in different experimental models. The action mechanisms of CGE suggest the reduction in the PGE2 levels. These findings support the use of cashew gum in popular medicine and demonstrate that part of its antinociceptive and anti-inflammatory effects should also be attributed to the presence of anacardic acids in its composition and independent of the presence of polysaccharides. Moreover, this study showed therapeutic potential of cashew gum for the development of analgesic and anti-inflammatory phytomedicines.

Uncovering the Formation of Color Gradients for Glucose Colorimetric Assays on Microfluidic Paper-Based Analytical Devices by Mass Spectrometry Imaging

Nonsteroidal anti-inflammatory drugs are commonly used worldwide; however, they have several adverse effects, evidencing the need for the development of new, more effective and safe anti-inflammatory and analgesic drugs. This research aimed to design, synthesize and carry out a pharmacological/toxicological investigation of LQFM-102, which was designed from celecoxib and paracetamol by molecular hybridization. To evaluate the analgesic effect of this compound, we performed formalin-induced pain, hot plate and tail flick tests. The anti-inflammatory effect of LQFM-102 was evaluated in carrageenan-induced paw oedema and pleurisy tests. The biochemical markers indicative of toxicity—AST, ALT, GSH, urea and creatinine—as well as the index of gastric lesion after prolonged administration of LQFM-102 were also analyzed. In addition, the interaction of LQFM-102 with COX enzymes was evaluated by molecular docking. In all experimental protocols, celecoxib or paracetamol was used as a positive control at equimolar doses to LQFM-102. LQFM-102 reduced the pain induced by formalin in both phases of the test. However, this compound did not increase the latency to thermal stimuli in the hot plate and tail flick tests, suggesting an involvement of peripheral mechanisms in this effect. Furthermore, LQFM-102 reduced paw oedema, the number of polymorphonuclear cells, myeloperoxidase activity and TNF-α and IL-1β levels. Another interesting finding was the absence of alterations in the markers of hepatic and renal toxicity or lesions of gastric mucosa. In molecular docking simulations, LQFM-102 interacted with the key residues for activity and potency of cyclooxygenase enzymes, suggesting an inhibition of the activity of these enzymes.