Navegando por Autor "Liao, Luciano Morais"
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- Item1H HR-MAS NMR and S180 cells: metabolite assignment and evaluation of pulse sequence(2014-04) Oliveira, Aline Lima de; Martinelli, Bruno César Barbosa; Liao, Luciano Morais; Pereira, Flávia de Castro; Lacerda, Elisângela de Paula Silveira; Alcantara, Glaucia BrazHigh resolution magic angle spinning 1H nuclear magnetic resonance spectroscopy (HR-MAS NMR) is a useful technique for evaluation of intact cells and tissues. However, optimal NMR parameters are crucial in obtaining reliable results. To identify the key steps for the optimization of HR-MAS NMR parameters, we assessed different pulse sequences and NMR parameters using sarcoma 180 (S180) cells. A complete assignment of the metabolites of S180 is given to assist future studies.
- Item1H HRMAS NMR spectroscopy and chemometrics for evaluation of metabolic changes in citrus sinensis caused by xanthomonas axonopodis pv. citri(2012-05) Silva, Lorena Mara Alexandre e; Alves Filho, Elenilson de Godoy; Choze, Rafael; Liao, Luciano Morais; Alcantara, Glaucia BrazXanthomonas axonopodis (Xac) bacterium causes one of the most feared and untreatable diseases in citriculture: citrus canker. To understand the response mechanisms of orange trees when attacked by Xac, leaves and fruits of Citrus sinensis were directly evaluated by HRMAS NMR (high resolution magic angle spinning nuclear magnetic resonance) spectroscopy. This technique allows the analysis of samples without laborious pre-treatments and also allows access to important information about chemical composition of samples. The orange tree leaves and fruit peels investigated in this study demonstrated the biochemical changes caused by Xac. Aided by chemometric analysis, the HRMAS NMR results show relevant changes in amino acids, carbohydrates, organic acids and terpenoids content.
- ItemAdsorption of organic acids from offshore produced water using microporous activated carbon from babassu pericarp: a low-cost alternative(2023) Mônaco, Felipe Santos; Aguiar, Deborah Victória Alves de; Oliveira, Gerlon de Almeida Ribeiro; Vaz, Boniek Gontijo; Liao, Luciano Morais; Andrade, Laiane Alves deCurrently, in different regions of the world, there is a growth on the rate of produced water for each barrel of oil extracted. Among the compounds observed in this water are naphthenic acids (NAs). Efforts to remove NAs from produced water must comply with local legislation and avoid damage to the environment since NAs have great toxicity. This study aimed to investigate the ability of activated carbon from the pericarp of babassu coconut (Atallea speciosa Mart. ex Spreng.) to act as an absorbent of NAs in commercial and natural (offshore) produced waters. The activated carbon was physically and chemically characterized. The maximum adsorption capacity of commercial NAs at equilibrium obtained experimentally was 25 mg g−1. The activated carbon removed both NAs and other contaminants for produced water, as revealed by infrared and NMR techniques. In high-resolution mass spectrometry analysis, the abundance of the acids in the produced water was in the C9 and C10 range, being favorable for the adsorbent with a microporous structure. For the produced water kinetics experiments a maximum amount of adsorbed compounds of 17.91 mg g−1 was reached, and the time to achieve equilibrium was approximately 180 min. Thus, the results show that activated charcoal from babassu coconut pericarp can be used as an adsorbent and can potentially compete with other adsorbents to remove NAs in an aqueous solution. Also, the separation process can be adopted at a low cost on platforms, complementing the operations of hydrocyclones and flotation.
- ItemAnalgesic and anti-inflammatory effects of Cheiloclinium cognatum root barks(2007-12) Costa, Elson Alves; Santos, Lúcio R.; Pontes, Itamar S.; Matos, Lécia Garcia de; Silva, Gilmar Aires da; Liao, Luciano MoraisCheiloclinium cognatum (Hippocrateaceae) has been used in folk medicine to treat fever and edema. In this paper, we report the anti-infl ammatory and analgesic activities of the crude dichloromethane extract (DECc) from C. cognatum root barks collected in Auguste de Saint Hilaire wood at Universidade Federal de Goiás. Doses of 0.1, 0.3 and 1.0 g/kg caused a dose-dependent inhibition of croton oil-induced ear edema in mice equivalent to 21, 30 and 51%, respectively. There was a signifi cant increase in analgesic-meter-induced tail fl ick test equivalent to 105, 189 and 200% of increase tail fl ick reaction time. These results allowed to suggest that C. cognatum could be a source of new compounds which anti-infl ammatory and analgesic activities.
- ItemAnti-inflammatory and antinociceptive activity profile of a new lead compound – LQFM219(2020) Galvão, Gustavo Mota; Florentino, Iziara Ferreira; Sanz Lobón, Germán; Vaz, Boniek Gontijo; Liao, Luciano Morais; Sabino, José Ricardo; Cardoso, Cariina Sofia; Silva, Daiany Priscilla Bueno da; Costa, Elson Alves; Silva, Andreia Luiza Pereira; Silva, Artur Christian Garcia da; Valadares, Marize Campos; Leite, Jacqueline Alves; Gil, Eric de Souza; Menegatti, RicardoLQFM219 is a molecule designed from celecoxibe (COX-2 inhibitor) and darbufelone (inhibitor of COX-2 and 5-LOX) lead compounds through a molecular hybridisation strategy. Therefore, this work aimed to investigate the antinociceptive and anti-inflammatory activities of this new hybrid compound. The acute oral systemic toxicity of LQFM219 was evaluated via the neutral red uptake assay. Acetic acid-induced abdominal writhing and CFA-induced mechanical hyperalgesia were performed to evaluate the antinociceptive activity, and the anti-oedematogenic activity was studied by CFA-induced paw oedema and croton oil-induced ear oedema. Moreover, the acute anti-inflammatory activity was determined by carrageenan-induced pleurisy. In addition, cell migration, myeloperoxidase enzyme activity, and TNF-α and IL-1β levels were determined in pleural exudate. Moreover, a redox assay was conducted using electroanalytical and DPPH methods. The results demonstrated that LQFM219 was classified as GHS category 4, and it showed better free radical scavenger activity compared to BHT. Besides, LQFM219 decreased the number of writhings induced by acetic acid and the response to the mechanical stimulus in the CFA-induced mechanical hyperalgesia test. Furthermore, LQFM219 reduced oedema formation, cell migration, and IL-1β and TNF-α levels in the pleural cavity and inhibited myeloperoxidase enzyme activity. Thus, our study provides that the new pyrazole derivative, LQFM219, demonstrated low toxicity, antinociceptive and anti-inflammatory potential in vitro and in vivo.
- ItemAnti-inflammatory effect of a new piperazine derivative: (4-methylpiperazin-1-yl)(1-phenyl-1H-pyrazol-4-yl)methanone(2017) Batista, Daniel da Costa; Silva, Daiany Priscilla Bueno da; Florentino, Iziara Ferreira; Cardoso, Carina Sofia; Gonçalves, Merita Pereira; Valadares, Marize Campos; Liao, Luciano Morais; Sanz Lobón, Germán; Vaz, Boniek Gontijo; Costa, Elson Alves; Menegatti, RicardoAims This study investigates the anti-nociceptive and anti-inflammatory effects of new piperazine compound (LQFM182) as well as the toxicity acute in vitro. Main methods To evaluate the anti-nociceptive activity, the acetic acid-induced abdominal writhing test, tail flick test and formalin-induced pain test were used. The anti-inflammatory activity was evaluated using the models of paw oedema and pleurisy induced by carrageenan and some inflammatory parameters were evaluated, including cell migration, myeloperoxidase enzyme activity and the levels of TNF-α and IL-1β cytokines in pleural exudate. The acute oral systemic toxicity of LQFM182 in mice was evaluated through the neutral red uptake (nru) assay. Key findings LQFM182 (50, 100 or 200 mg/kg, p.o.) decreased the number of writhings induced by acetic acid in a dose-dependent manner, and an intermediate dose (100 mg/kg, p.o.) reduced the paw licking time of animals in the second phase of the formalin test. Furthermore, LQFM182 (100 mg/kg, p.o.) reduced oedema formation at all hours of the paw oedema induced by carrageenan test and in pleurisy test reduced cell migration from the reduction of polymorphonuclear cells, myeloperoxidase enzyme activity and the levels of pro-inflammatory cytokines IL-1β and TNF-α. Therefore, it was classified in GHS category 300 < LD50 < 2000 mg/kg.
- ItemAnti-inflammatory, antinociceptive, and vasorelaxant effects of a new pyrazole compound 5-(1-(2-fluorophenyl)-1H-pyrazol-4-yl)-1H-tetrazole: role of NO/cGMP pathway and calcium channels(2023) Oliveira, Lanussy Porfiro de; Florentino, Iziara Ferreira; Silva, Daiany Priscilla Bueno da; Pazini, Francine; Carvalho, Flávio Silva de; Sanz Lobón, Germán; Vaz, Boniek Gontijo; Rocha, Fabio Fagundes da; Fajemiroye, James Oluwagbamigbe; Ghedini, Paulo César; Liao, Luciano Morais; Menegatti, Ricardo; Costa, Elson Alves; Oliveira, Thiago Sardinha deMolecular modification of compounds remains important strategy towards the discovery of new drugs. In this sense, this study presents a new pyrazole derivative 5-(1-(2-fluorophenyl)-1H-pyrazol-4-yl)-1H-tetrazole (LQFM039) and evaluated the anti-inflammatory, analgesic, and vasorelaxant effects of this compound as well the mechanisms of action involved in the pharmacological effects. For this, mice were orally treated with LQFM039 (17.5, 35, or 70 mg/kg) prior acetic acid-induced abdominal writhing, formalin, tail flick, and carrageenan-induced paw edema protocols. In addition, vascular reactivity protocols were made with aortic rings contraction with phenylephrine and stimulated with graded concentrations of LQFM039. Abdominal writhing and licking time in both neurogenic and inflammatory phases of formalin were reduced with LQFM039 without altering latency to nociceptive response in the tail flick test. Carrageenan-induced paw edema showed that LQFM039 reduces edema and cell migration. In addition, the mechanism of action of LQFM039 involves NO/cGMP pathway and calcium channels, since this new pyrazole derivate elicited concentration-dependent relaxation attenuated by Nω-nitro-l-arginine methyl ester and 1H-[1,2,4] oxadiazolo [4,3-alpha]quinoxalin-1-one, and blockade of CaCl2-induced contraction. Altogether, our finding suggests anti-inflammatory, antinociceptive, and vasorelaxant effect of this new pyrazole derivative with involvement of NO/cGMP pathway and calcium channels.
- ItemAntiangiogenic and antitumoral activity of LQFM126 prototype against B16F10 melanoma cells(2020) Silva, Artur Christian Garcia da; Rodrigues, Bruna dos Santos; Andrade, Wanessa Machado; Santos, Thaís Rosa Marques dos; Flávio Silva de Carvalho; Sanz Lobón, Germán; Vaz, Boniek Gontijo; Liao, Luciano Morais; Menegatti, Ricardo; Valadares, Marize CamposInhibition of mouse double minute 2 homolog (MDM2)-p53 interaction and reactivation of p53 signaling have been explored as effective anticancer therapeutic strategy. The potent and specific antitumor activity shown by Nutlins, first class of MDM2-p53 inhibitors discovered, has made these compounds potential antitumor candidates. To this end, we synthesized Nutlin-1 and Nutlin-2 analogs through molecular simplification and selected the compound with the most efficient antitumoral activity. Cytotoxicity of Nutlin-2 analog LQFM126 on B16F10 melanoma cells induced intense cytoplasmic vacuolization, reduction of cell size, chromatin condensation, cytoplasmic degeneration and nuclear fragmentation. LQFM126 antiproliferative effects mediated cell cycle retention in G0/G1 phase and increased the levels of cell cycle regulatory proteins p21 and p27. This Nutlin analog increased mitochondrial membrane potential, activated caspase-8, -9 and -3/7 and reduced VEGF levels in B16F10 cells. Therefore, LQFM126 promoted alterations suggestive of apoptosis, G0/G1 cell cycle arrest and suppression of angiogenesis through modulation of VEGF expression in B16F10 cells. Additionally, LQFM126 was classified as UN GHS category 4 (LD50 > 300–2000 mg/kg), suggesting it has low acute systemic toxicity. LQFM126 can be a promising prototype for anticancer therapy.
- ItemAnxiolytic- and antidepressant-like effects of new phenylpiperazine derivative LQFM005 and its hydroxylated metabolite in mice(2022) Moreira, Lorrane Kelle da Silva; Silva, Rafaela Ribeiro; Silva, Dayane Moreira da; Silva, Mirella Andrade; Brito, Adriane Ferreira de; Sanz Lobón, Germán; Silva, Artur Christian Garcia da; Oliveira, Valéria de; Vaz, Boniek Gontijo; Liao, Luciano Morais; Costa, Elson Alves; Menegatti, RicardoThe current treatments available for anxiety and depression are only palliative. Full remission has remained elusive, characterizing unmet medical needs. In the scope of an academic drug discovery program, we describe here the design, synthesis, in vitro metabolism prediction and pharmacological characterization of a new piperazine compound, 1-(4-methoxyphenyl)−4-((1-phenyl-1H-pyrazol-4-yl)methyl)piperazine (LQFM005), and of its main putative metabolite, 4-(4-((4-(4-methoxyphenyl)piperazin-1-yl)methyl)− 1H-pyrazol-1-yl)phenol (LQFM235). The production of the metabolite was initially performed by in vitro biotransformation of LQFM005 using Aspergillus candidus and then by chemical synthesis. Oral administration of either 12 or 24 µmol/kg LQFM005 to mice did not affect spontaneous locomotor activity but increased the time spent in the center of the open field. Both LQFM005 and LQFM235 (24 µmol/kg) increased the time spent by the mice in the open arms of the elevated plus maze (EPM), a good indication of anxiolytic-like effect, and decreased the immobility time in the forced swimming test (FST), suggesting an antidepressant-like effect. The previous administration of WAY-100635 (a 5-HT1A antagonist) abolished the effects of LQFM005 in both EPM and FST. Binding experiments showed that LQFM005 and its metabolite bind to the 5-HT1A receptor with a moderate affinity (Ki around 5–9 µM). The two compounds are relatively safe, as indicated by cytotoxic assessment using the 3T3 fibroblast cell line and estimated LD50 around 600 mg/kg. In conclusion, oral administration of the newly synthesized phenylpiperazines produced anxiolytic- and antidepressant-like effects in behavioral tests, putatively in part through the activation of 5-HT1A receptors.
- ItemAnxiolytic-like effect of 2-(4-((1-phenyl-1H-pyrazol-4-yl)methyl)piperazin-1-yl)ethan-1-ol is mediated through the benzodiazepine and nicotinic pathways(2017) Brito, Adriane Ferreira de; Fajemiroye, James Oluwagbamigbe; Neri, Hiasmin Franciely da Silva; Silva, Dayane Moreira da; Silva, Daiany Priscilla Bueno da; Sanz Lobón, Germán; Vaz, Boniek Gontijo; Carvalho, Flávio Silva de; Ghedini, Paulo César; Liao, Luciano Morais; Menegatti, Ricardo; Costa, Elson AlvesIn this study, we proposed the design, synthesis of a new compound 2-(4-((1-phenyl-1H-pyrazol-4-yl)methyl)piperazin-1-yl)ethan-1-ol (LQFM032), and pharmacological evaluation of its anxiolytic-like effect. This new compound was subjected to pharmacological screening referred to as Irwin test, prior to sodium pentobarbital-induced sleep, open-field and wire tests. The anxiolytic-like effect of this compound was evaluated using elevated plus maze and light–dark box tests. In addition, the mnemonic activity was evaluated through step-down test. In sodium pentobarbital-induced sleep test, LQFM032 decreased latency and increased duration of sleep. In the open-field test, LQFM032 altered behavioral parameter, that suggested anxiolytic-like activity, as increased in crossings and time spent at the center of open field. In the plus maze test and light–dark box test, the LQFM032 showed anxiolytic-like activity, increased entries and time spent on open arms, and increased in number of transitions and time spent on light area, respectively. Those effects was antagonized by flumazenil but not with 1-(2-Methoxyphenyl)-4-(4-phthalimidobutyl)piperazine (NAN-190). The LQFM032 did not alter mnemonic activity. Moreover, the anxiolytic-like activity of LQFM032 was antagonized by mecamylamine. In summary, LQFM032 showed benzodiazepine and nicotinic pathways mediated anxiolytic-like activity without altering the mnemonic activity.
- ItemChemotaxonomic significance of flavonoids, coumarins and triterpenes of Augusta longifolia (Spreng.) Rehder, Rubiaceae-Ixoroideae, with new insights about its systematic position within the family(2010-07) Choze, Rafael; Delprete, Piero Giuseppe; Liao, Luciano MoraisAugusta has traditionally been placed in the tribe Rondeletieae, subfamily Cinchonoideae. However, recent molecular phylogenies positioned it near to Wendlandia (Ixoroideae), but locate A. longifolia near to the clade Ixoroidinae II. The study of A. longifolia afforded two coumarins, five flavonoids, three triterpenoids and one benzoic acid derivative. These metabolites reinforce the separation of Augusta as a monospecific genus, and Lindenia as a genus of three species, closely related to Wendlandia.
- ItemDesign, synthesis and pharmacological assessment of new pyrazole compounds(2020) Barbosa, Jordana Cristina Oliveira; Silva, Daiany Priscilla Bueno da; Florentino, Iziara Ferreira; Silva, Lidya Cardozo da; Sanz Lobón, Germán; Vaz, Boniek Gontijo; Pazini, Francine; Carvalho, Flávio Silva de; Liao, Luciano Morais; Santos, Thaís Rosa Marques dos; Valadares, Marize Campos; Costa, Elson Alves; Santos, Fernanda Cristina Alcantara dos; Villavicencio, Bianca; Verli, Hugo; Menegatti, RicardoAims This study investigated the antinociceptive and anti-inflammatory effects of new pyrazole compounds LQFM011(5), LQFM043(6) and LQFM044(7) as well as the mechanisms of action and acute in vitro toxicity. Main methods The antinociceptive activity was evaluated using the acetic acid-induced abdominal writhing test, formalin-induced pain test and the Randall–Selitto test. The anti-inflammatory activity was evaluated using models of paw oedema and pleurisy induced by carrageenan; cell migration, the levels of tumour necrosis factor α (TNF-α) and myeloperoxidase (MPO) enzyme activity were evaluated. In addition, the ability to inhibit phospholipase A2 (PLA2) in vitro and docking in PLA2 were used. Acute oral systemic toxicity in mice was evaluated through the neutral red uptake assay. Key findings The synthesised compounds (5–7), delivered via gavage (p.o.) at 70, 140 or 280 µmol/kg, decreased the number of writhings induced by acetic acid; the three compounds (280 µmol/kg p.o.) reduced the paw licking time in the first and second phase of the formalin test and decreased the nociceptive threshold variation in the Randall–Selitto test. Furthermore, this dose reduced oedema formation, leucocyte migration (specifically through reduction in polymorphonuclear cell movement) and increased mononuclear cells. MPO activity and the levels of pro-inflammatory cytokines TNF-α were decreased. Evaluation of PLA2 inhibition via the docking simulation revealed more interactions of LQFM043R(6) and LQFM044(7), data that corroborated the half-maximal inhibitory concentration (IC50) of PLA2 inhibition in vitro. Therefore, LQFM011(5), LQFM043(6) and LQFM044(7) were classified with the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) as category 4.
- ItemDesign, synthesis and pharmacological evaluation of new anti-inflammatory compounds(2016-08-30) Cidade, Amanda Feitosa; Corrêa, Patricia Antônia Vasconcelos; Silva, Daiany Priscilla Bueno da; Florentino, Iziara Ferreira; Vasconcelos, Géssica Adriana; Vaz, Boniek Gontijo; Costa, Elson Alves; Liao, Luciano Morais; Menegatti, RicardoInflammatory 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 LQFM146, LQFM-147 or LQFM-148 at doses 89, 178 and 356 mmol/kg p.o. reduced the abdominal writhing in a dose-dependent manner. In the formalin test, these compounds at dose 178 mmol/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 (178 mmol/ 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.
- ItemDiscrimination of sugarcane according to cultivar by ¹H NMR and chemometric analyses(2012-12) Alves Filho, Elenilson de Godoy; Silva, Lorena Mara Alexandre e; Choze, Rafael; Liao, Luciano Morais; Honda, Neli Kika; Alcantara, Glaucia BrazSeveral technologies for the development of new sugarcane cultivars have mainly focused on the increase in productivity and greater disease resistance. Sugarcane cultivars are usually identified by the organography of the leaves and stems, the analysis of peroxidase and esterase isoenzyme activities and the total soluble protein as well as soluble solid content. Nuclear magnetic resonance (NMR) associated with chemometric analysis has proven to be a valuable tool for cultivar assessment. Thus, this article describes the potential of chemometric analysis applied to 1H high resolution magic angle spinning (HRMAS) and NMR in solution for the investigation of sugarcane cultivars. For this purpose, leaves from eight different cultivars of sugarcane were investigated by 1H NMR spectroscopy in combination with chemometric analysis. The approach shows to be a useful tool for the distinction and classification of different sugarcane cultivars as well as to access the differences on its chemical composition.
- ItemHR-MAS NMR allied to chemometric on hancornia speciosa varieties differentiation(2018) Flores, Igor Savioli; Silva, Andressa Kuhnen; Furquim, Leonnardo Cruvinel; Castro, Carlos Frederico de Souza; Chaves, Lázaro José; Collevatti, Rosane Garcia; Liao, Luciano MoraisThis work describes the potential of chemometric analyses applied to 1H high-resolution magic angle spinning nuclear magnetic resonance (1H HR-MAS NMR) data for the chemotaxonomic investigation of Hancornia speciosa (Apocynaceae) varieties. This plant, popularly known as mangaba, has a complex morphological differentiation and thus chemical analyses can be used for their taxonomic classification. In comparison to traditional techniques, 1H HR-MAS NMR allied with chemometrics provided a simple and low cost method for chemotaxonomy. Leaves of four varieties of H. speciosa from a common garden experiment was studied and demonstrated that H. speciosa var. speciosa differs from others due to its specific metabolic profile, and var. pubescens was discriminated based on its high phenolic compound content. The distinction between the latter variety and gardineri is important once it allows for the selection of samples with greater commercial value, once they produce the largest and heaviest fruits.
- ItemInvestigation of anti-inflammatory potential of 5-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-thioxodihydropyrimidine-4,6 (1H,5H)-dione compound(2020) Almeida, Dionys de Souza; Silva, Daiany Priscilla Bueno da; Moreira, Lorrane Kelle da Silva; Menegatti, Ricardo; Liao, Luciano Morais; Sanz, Germán; Vaz, Boniek Gontijo; Ghedini, Paulo César; Costa, Elson Alves; Florentino, Iziara FerreiraThe aim of this study was to synthesise the novel di-tert-butylphenol compound, 5-(3,5-di-tert-butyl-4-hydroxybenzylidene)-2-thioxo-dihydropyrimidine-4,6(1H, 5H)-dione (LQFM218), and evaluate the potential antinociceptive and anti-inflammatory activities in acute (mice) models in vivo. The compound was tested on acute models of pain such as acetic acid-induced abdominal writhing, formalin-induced nociception and carrageenan-induced mechanical hyperalgesia. The anti-inflammatory activity was observed in paw oedema, carrageenan-induced pleurisy tests and inflammatory mediator quantification. Key findings: oral treatment with the LQFM218 (50, 100 or 200 mg/kg) reduced abdominal writhing (18.8%, 31.6% and 48.3%). The dose intermediate (100 mg/kg) reduced the nociception in the second phase of the formalin test (61.4%), and also showed anti-hyperalgic activity in carrageenan-induced mechanical hyperalgesia (until 42.3%). In acute inflammation models, the treatment of mice LQFM218 (100 mg/kg) reduced the paw oedema all the time (33.8%, 42.6%, 37.4% and 36%) and in pleurisy test reduced: polymorphonuclear cell migration (35.4%), myeloperoxidase activity (52.2%) and the levels of inflammatory mediators such as PGE2 (23.0%), TNF-α (67.6%) and IL-1β (53.4%). The present study showed that LQFM218 effectively reduced the nociception and inflammation in different models, and its mechanism might be related to the reduction of PGE2 and proinflammatory cytokines. These findings show LQFM218 as a potential anti-inflammatory drug.
- ItemIsolation and structural characterization of two new furanoditerpenes from Pterodon emarginatus (Fabaceae)(2017) Oliveira, Leandra de Almeida Ribeiro; Oliveira, Gerlon de Almeida Ribeiro; Lemes, Geralda de Fátima; Romão, Wanderson; Vaz, Boniek Gontijo; Albuquerque, Sérgio de; Rotta, Cristiana Gonçalez; Liao, Luciano Morais; Bara, Maria Teresa FreitasA furanoditerpene-enriched fraction was obtained from the fruits of Pterodon emarginatus and submitted to semipreparative high performance liquid chromatography (HPLC). Two new furanoditerpenes, 6α,19β-diacetoxy-7β,14β-dihydroxyvouacapan and 6α-acetoxy7β,14β-dihydroxyvouacapan, in addition to the known compound methyl 6α-acetoxy7β-hydroxyvouacapan-17β-oate were obtained. Compound structures were determined by 1D and 2D nuclear magnetic resonance (NMR) experiments and electrospray ionization Fourier transform ion cyclotron resonance mass spectrometry (ESI-FTICR-MS). The major compound methyl 6α-acetoxy-7β-hydroxyvouacapan-17β-oate was evaluated against promastigote forms of Leishmania amazonensis and L. braziliensis, presenting the concentration which causes lysis on 50% of parasites IC50 < 30 µg mL-1.
- ItemLQFM184: a novel wide ultraviolet radiation range absorber compound(2021) Vinhal, Daniela Cristina; Marcelino, Renato Ivan de Ávila; Gomes, Thaisângela Rodrigues Lopes e Silva; Silva, Andressa Kuhnen; Moreira, Larissa Cleres; Valadares, Marize Campos; Luzin, Rangel Magalhães; Liao, Luciano Morais; Gil, Eric de Souza; Vaz, Boniek Gontijo; Assis, Rogério Jorge de; Gonçalves, Pablo José; Isaac, Vera Lucia Borges; Cunha, Luiz Carlos da; Menegatti, RicardoThe use of sunscreen has become an indispensable daily routine since UV radiation is a critical environmental stress factors for human skin. This study focused on the design, synthesis, thermal/chemical stability and efficacy/safety evaluations of a new heterocyclic derivative, namely LQFM184, as a photoprotective agent. The compound showed stability when submitted under oxidative and high-temperature conditions. It also revealed an absorption at 260–340 nm (UVA/UVB), with a main band at 298 nm and a shoulder close to 334 nm. LQFM184 showed capacity to interact with other existing UV filters, promoting an increase in the sun protection factor. In relation to acute toxicity, its estimated LD50 was >300–2000 mg kg−1, probably with a low potential of inducing acute oral systemic toxicity hazard. In addition, our data showed that this compound did not have eye irritation, skin sensitization or phototoxicity potentials. Taken together, these findings make LQFM184 a promising ingredient to be used, alone or in association with other UV filters, in cosmetic products such as sunscreens with a broad spectrum of protection.
- ItemMechanisms involved in the antinociceptive and anti-inflammatory effects of a new triazole derivative: 5-[1-(4-fluorophenyl)-1H-1,2,3-triazol-4-yl]-1H-tetrazole (LQFM-096)(2020) Cardoso, Carina Sofia; Silva, Daiany Priscilla Bueno da; Silva, Dayane Moreira da; Florentino, Iziara Ferreira; Fajemiroye, James Oluwagbamigbe; Moreira, Lorrane Kelle da Silva; Vasconcelos, Jose Pacifico de; Sanz Lobón, Germán; Vaz, Boniek Gontijo; Liao, Luciano Morais; Santos, Fernanda Cristina Alcantara dos; Menegatti, Ricardo; Costa, Elson AlvesThe aim of this study was to design, synthesize and evaluate the potential analgesic and anti-inflammatory effects of 5-[1-(4-fluorphenyl)-1H-1,2,3-triazol-4-yl]-1H-tetrazole—(LQFM-096: a new triazole compound) as well as to elucidate its possible mechanisms of action. The oral administration of LQFM-096 (10, 20 or 40 mg/kg) decreased the number of writhing in mice. At the dose of 20 mg/kg, LQFM-096 reduced the licking time at both neurogenic and inflammatory phases of the formalin test. Pretreatment with naloxone (3 mg/kg) and glibenclamide (3 mg/kg) attenuated the antinociceptive effect of LQFM-096 in the first phase of the formalin test. At the dose of 20 mg/kg, LQFM-096 also decreased the licking time in the acidified saline-induced and capsaicin-induced nociception. This effect was blocked by naloxone (3 mg/kg) pretreatment prior to the administration of LQFM-096. In addition, LQFM-096 inhibited hyperalgesia induced by carrageenan and PGE2. Naloxone (3 mg/kg) attenuated the effect of LQFM-096 through disinhibition of PGE2-induced hyperalgesia. The anti-inflammatory effect of LQFM-096 was demonstrated in carrageenan-induced oedema or pleurisy as well as CFA-induced arthritis. The hyperalgesia and cellular migration in CFA-induced arthritis were reduced significantly. Altogether, these findings suggest antinociceptive effect of LQFM-096 and implicate the modulation of ASICs/TRPV1 channels by opioid/KATP pathway. The anti-inflammatory effect of LQFM-096 was mediated by a reduction in oedema, leukocytes migration, TNF-α, PGE2 levels and myeloperoxidase activity.
- ItemMolecular docking and pharmacological/toxicological assessment of a new compound designed from celecoxib and paracetamol by molecular hybridization(2018) Silva, Daiany Priscilla Bueno da; Florentino, Iziara Ferreira; Silva, Dayane Moreira da; Lino, Roberta Campos; Cardoso, Carina Sofia; Moreira, Lorrane Kelle da Silva; Vasconcelos, Géssica Adriana; Vaz, Boniek Gontijo; Liao, Luciano Morais; Cunha, Luiz Carlos da; Menegatti, Ricardo; Costa, Elson AlvesNonsteroidal 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.