Navegando por Autor "Santos, Marcelo Henrique dos"
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Item 2,2’,4-Trihydroxybenzophenone : crystal structure, and anti-inflammatory and antioxidant activities.(2007) Doriguetto, Antônio Carlos; Martins, Felipe Terra; Ellena, Javier Alcides; Salloum, Rogério; Santos, Marcelo Henrique dos; Moreira, Maria Eliza de Castro; Silva, Jose Mauricio Schneedorf Ferreira da; Nagem, Tanus JorgeThe crystal structure of C 2,2’,4-trihydroxybenzophenoneD (¼(2,4-dihydroxyphenyl)(2-hydroxyphenyl) methanone; 1) was determined, and its molecular structure, along with intra- and intermolecular Hbonds, was analyzed. The anti-inflammatory potential of 1, evaluated by means of the rat-paw-edema assay, with carrageenan as inflammation stimulus, was found to be similar high as that of indomethacin. In contrast, benzophenone proper (2) was hardly active in this assay. Our results indicate that these antiinflammatory effects are related to the action of kinins and prostaglandins. The radical-scavenging properties of 1 towards DPPH were found to be similar as those of typical phenolics, but somewhat lower than that of ascorbic acid. The structure–activity relationship (SAR) of 1 is discussed.Item Antimicrobial activity of Rheedia brasiliensisand 7-epiclusianone against Streptococcus mutans.(2008) Almeida, Luciana Salles Branco de; Murata, Ramiro Mendonça; Yatsuda, Regiane; Santos, Marcelo Henrique dos; Nagem, Tanus Jorge; Alencar, Severino Matias de; Koo, Hyun; Rosalen, Pedro LuizThis in vitro study evaluated the antimicrobial activity of extracts obtained from Rheedia brasiliensis fruit (bacupari) and its bioactive compound against Streptococcus mutans. Hexane, ethyl-acet ate and ethanolic extracts obtained (concentrations ranging from 6.25 to 800mg/ml) were tested against S. mutans UA1 59 through MIC /MBC assays. S. mutans5-days -old biofilm s were treat ed with the active extra cts (100 MIC ) for 0, 1, 2, 3 an d 4 h (time-k ill) and plate d for colony counting (CFU/m l). Active extracts were submitted to exploratory chemical analyses so as to isolate and identify the bioactive compound using spectroscopic method s. The bioactive compo und (concentration s ranging from 0.625 to 80mg/ml) was then tested through MIC /MBC assays . Pee l and seed hexane extracts showed antimicrobial activity against planktonic cells at low concentrations and were thus selected for the time kill test. These hexane extracts reduced S. mutans biofilm viability after 4 h, certifying of the bioactive compo und presence. The bioactive compound identified was the polyprenylated benzophenone 7-epiclusianone, which showed a good antimicrobial activity at low concentrations (MIC : 1.25–2 .5 mg/ml; MBC: 10–20mg/ml). The results indicated that 7-epi clusian one may be used as a ne w agent to control S. mutans biofilms; however, more studies are needed to further elucidate the mechanisms of action and the anticariogenic potential of such compound found in R. brasiliensis.Item Antioxidant, cytotoxic and antimutagenic activities of 7-epi-clusianone obtained from pericarp of Garcinia brasiliensis.(2012) Silva, Luciano Bruno Carvalho; Oliveira, Maysa do Vale; Gontijo, Vanessa Silva; Oliveira, Williana Fernandes de; Derogis, Priscilla Bento Matos Cruz; Stringheta, Paulo César; Nagem, Tanus Jorge; Brigagão, Maísa Ribeiro Pereira Lima; Santos, Marcelo Henrique dosThis paper describes the investigation of the cytotoxic and antioxidant activities and in vivo mutagenic/ antimutagenic potential of different concentrations of the hexane extract (EHP) and isolated molecule 7-epi-clusianone (MI) of Rheedia brasiliensis. The in vitro antioxidant activity of MI was investigated by monitoring the reduction of radical scavenging and metal chelating activity of DPPH (1,1-diphenyl-2-picrylhydrazil). Cytotoxic activity was assessed by measuring the mortality of brine shrimp in the presence and absence of the compounds. The mutagenic, antimutagenic and cytotoxic effects of these compounds were evaluated by a micronucleus test. During the antioxidant activity assessment, the 7-epi-clusianone was significantly higher than that of EHP at all concentrations in three assays. From the results obtained with the assessment of cytotoxic activity, all samples had a mortality rate (LC50b100 mg/mL) lower than the positive control (thymol). The results of the micronucleus test revealed that MI at 5, 10 and 15 mg/kg b.w. is antimutagenic. In conclusion, these results suggest that in the future, the EHP and MI could be used as prophylactic agents in cancer prevention.Item Antiproliferative effect of benzophenones and their infl uence on cathepsin activity.(2010) Murata, Ramiro Mendonça; Yatsuda, Regiane; Santos, Marcelo Henrique dos; Kohn, Luciana K.; Martins, Felipe Terra; Nagem, Tanus Jorge; Alencar, Severino Matias de; Carvalho, João Ernesto de; Rosalen, Pedro LuizThe antiproliferative activity of two prenylated benzophenones isolated from Rheedia brasiliensis, the triprenylated garciniaphenone and the tetraprenylated benzophenone 7-epiclusianone, was investigated against human cancer cell lines. The antiproliferative activity on melanoma (UACC-62), breast (MCF-7), drug-resistant breast (NCI-ADR), lung/non-small cells (NCI460), ovarian (OVCAR 03), prostate (PC03), kidney (786-0), lung (NCI-460) and tongue (CRL-1624 and CRL-1623) cancer cells was determined using spectrophotometric quantifi cation of the cellular protein content. The effect of these benzophenones on the activity of cathepsins B and G was also investigated. Garciniaphenone displayed cytostatic activity in all cell lines, whereas 7- epiclusianone showed a dose-dependent cytotoxic effect. The IC50 values for cell proliferation revealed that 7-epiclusianone is more active than garciniaphenone against most of the cell lines. Furthermore, the antiproliferative effects demonstrated by garciniaphenone and 7-epiclusianone were related to their cathepsin inhibiting properties. In conclusion, 7-epiclusianone is a promising naturally occurring agent which displays multiple inhibitory effects which may be working in concert to inhibit cancer cell proliferation in vitro. The putative pathway by which 7-epiclusianone affects cancer cell development may involve cathepsin inhibition.Item Benzophenone derivatives showed dual anti-inflammatory and antiproliferative activities by inhibiting cox enzymes and promote cyclin e downregulation.(2022) Folquitto, Laís Regina dos Santos; Souza, Thiago Belarmino de; Januário, Jaqueline Pereira; Nascimento, Isadora M.; Brandão, Brenda Tavares de Vasconcelos; Moreira, Maria E. C.; Horvath, Renato de Oliveira; Santos, Marcelo Henrique dos; Coelho, Luiz Felipe Leomil; Veloso, Marcia Paranho; Soares, Marisi Gomes; Carvalho, Diogo Teixeira; Ionta, Marisa; Paula, Daniela Aparecida Chagas de; Dias, Danielle FerreiraConsidering the promising antitumor effects of compounds with dual anti-inflammatory and antiproliferative activities, thus benzophenones analogs (2-7) were evaluated on in vivo anti- inflammatory assay and molecular docking analysis. Those with the best molecular docking results were in vitro evaluated on cyclooxygenase (COX) enzymes and tested regarding antiproliferative activity. All derivatives displayed in vivo anti-inflammatory activity. Among them, the substances 2’-hydroxy-4’-benzoylphenyl-β-D-glucopyranoside (4), 4-hydroxy-4’-methoxybenzophenone (5) and 4’-(4’’-methoxybenzoyl)phenyl-β-D-glucopyranoside (7)showed the best values of Glide Score in COX-2 docking evaluation and 4 and 5 selectively inhibited COX-2 and COX-1 in vitro enzymatic assay, respectively. Thus, 4 and 5 were tested against breast cancer (MCF-7, MDA-MB-231, Hs578T) and non-small-cell-lung cancer (A549) cell lines. The estrogen-positive MCF-7 cell line was more responsive compared to other tested cell lines. They induced cell cycle arrest at G1/S transition in MCF-7 cell line once there was an increase in G0/G1 population with concomitant reduction of S population. The antiproliferative activity of these substances on MCF-7 was associated with their ability to inhibit cyclin E expression, a critical regulator of G1/S transition. Taken together, the data indicate that 4 and 5 have dual anti-inflammatory and antiproliferative activities and support further studies to evaluate their antitumor potential.Item Complete assignment of the 1H and 13C NMR spectra of a new polyester sesquiterpene from Austroplenckia populnea.(2000) Vieira Filho, Sidney Augusto; Duarte, Lucienir Pains; Santos, Marcelo Henrique dos; Silva, Grácia Divina de Fátima; Lula, Ivana Silva; Afonso, Robson José de Cássia Franconew polyester sesquiterpene (4-hydroxy-1,2,6,15-tetraacetyl-9-benzoylagarofuran), together with known friedelane triterpenes (friedelin, -friedelinol and 28-hydroxyfriedelin), was isolated from the leaves of Austroplenckia populnea. The structure and relative stereochemistry of the new ester were based on 2D NMR spectroscopic techniques including HMBC, HMQC and NOESY.Item Complete assignment of the 1H and 13C NMR spectra of the tetraisoprenylated benzophenone 15-epiclusianone.(2001) Santos, Marcelo Henrique dos; Nagem, Tanus Jorge; Braz Filho, Raimundo; Lula, Ivana Silva; Speziali, Nivaldo LucioAn NMR study of 15-epiclusianone, 1-benzoyl-6-hydroxy-14,14-dimethyl-3,5,15-tri(3-methyl-2-butenyl)- bicyclo[3.3.1]non-1-ene-4,6-dione (1), a novel tetraisoprenylated benzophenone isolated from pericarp of fruits of Rheedia gardneriana, is described. In addition to conventional 1D NMR techniques, 2D shiftcorrelated NMR experiments [1H 1H-COSY, 1H 13C-HMQC-1J(C,H), 1H 13C-HMBC-nJ(C,H) (n = 2 and 3) and 1H 1H-NOESY] were used for 1H and 13C chemical shift assignments of this natural product. The 1D 13C NMR spectrum of 1 in the solid state was also obtained.Item Design and synthesis of new benzophenone derivatives with in vivo anti-inflammatory activity through dual inhibition of edema and neutrophil recruitment.(2018) Januário, Jaqueline Pereira; Souza, Thiago Belarmino de; Lavorato, Stefânia Neiva; Maiolini, Tatiane Cristina Silva; Domingos, Olívia da Silva; Zanin, João Luiz Baldim; Folquitto, Laís Regina dos Santos; Soares, Marisi Gomes; Paula, Daniela Aparecida Chagas de; Dias, Danielle Ferreira; Santos, Marcelo Henrique dosA series of novel benzophenone derivatives containing a thiazole heterocyclic nucleus were designed by molecular hybridization. Molecular docking studies have demonstrated the inhibitory potential of the designed compounds against cyclooxygenase (COX) isoenzymes. These compounds were synthesized, characterized, and evaluated for their anti-inflammatory properties by the croton oil-induced ear edema assay to examine their effect on both prostaglandin (PG) production and neutrophils recruitment. The thiazole derivatives displayed a potent effect in terms of reducing ear edema. The analysis suggested that the presence of 4-phenyl-2-hydrazinothiazole and the absence of C40 -OCH3 on the benzophenone derivative structure are strongly related to the inhibition of PG production. In addition, the derivatives 2e, 3a and 3c concomitantly inhibit PG production and neutrophil recruitment, which may be a mechanism of action better than of common NSAIDs due to their inability to inhibit the neutrophil recruitment. Thus, these compounds can be considered as potential lead compounds toward the development of new anti-inflammatory drugs with an innovating mechanism of actionItem Efeito de constituintes químicos isolados da casca do fruto de Rheedia gardneriana sobre a eclosao de juvenis de Meloidogyne incognita raça 3.(2007) Santos, Marcelo Henrique dos; Correa, Rodrigo de Souza; Rocha, Miguel D.; Nagem, Tanus Jorge; Oliveira, Tânia Toledo de; Oliveira, Rosângela D'Arc de Lima; Oliveira, José Rogério deOs constituintes químicos isolados do fruto (pericarpo) de Rheedia gardneriana (“bacupari”), foram identificados como 7-epiclusianona (I), o ácido oleanólico (II) e uma mistura de sesquiterpenos (III) e testados, in vitro, quanto à sua atividade biológica sobre a eclosão de juvenis do nematóide Meloidogyne incognita raça 3 na concentração de 100 μg.mL–1. Os resultados mostraram que o ácido oleanólico foi o mais eficiente, com uma taxa de inibição de eclosão de juvenis de 40,46%, caracterizada como um efeito nematostático, uma vez que a eclosão de juvenis ocorreu quando os ovos tratados pela substância foram transferidos para a água.Item Inhibition of cysteine proteases by a natural biflavone : behavioral evaluation of fukugetin as papain and cruzain inhibitor.(2012) Assis, Diego Magno; Gontijo, Vanessa Silva; Pereira, Ivan de Oliveira; Santos, Jorge Alexandre Nogueira; Camps, Ihosvany; Nagem, Tanus Jorge; Izidoro, Mario Augusto; Tersariol, Ivarne Luis dos Santos; Barros, Nilana Meza Tenório de; Doriguetto, Antônio Carlos; Santos, Marcelo Henrique dos; Juliano, Maria AparecidaCruzain is the major cysteine protease of Trypanosoma cruzi, the infectious agent responsible for Chagas disease, and cruzain inhibitors display considerable antitrypanosomal activity. In the present work we elucidated crystallographic data of fukugetin, a biflavone isolated from Garcinia brasiliensis, and investigated the role of this molecule as cysteine protease inhibitor. The kinetic analyses demonstrated that fukugetin inhibited cruzain and papain by a slow reversible type inhibition with KI of 1.1 and 13.4 μM, respectively. However, cruzain inhibition was about 12 times faster than papain inhibition. Lineweaver–Burk plots demonstrated partial competitive inhibition for cruzain and hyperbolic mixed-type inhibition for papain. Furthermore, the docking results showed that the biflavone binds to ring C′ in the S2 pocket and to ring C in the S3 pocket through hydrophobic interactions and hydrogen bonds. Finally, fukugetin also presented inhibitory activity on proteases of the T. cruzi extract, with IC50 of 7 μM.Item Inhibitory efects of 7-epiclusianone on glucan synthesis, acidogenicityand biofilm formation by Streptococcus mutans.(2008) Murata, Ramiro Mendonça; Almeida, Luciana Salles Branco de; Yatsuda, Regiane; Santos, Marcelo Henrique dos; Nagem, Tanus Jorge; Rosalen, Pedro Luiz; Koo, HyunThe aim of this study was to examine the effects of 7-epiclusianone, a new prenylated benzophenone isolated from the plant Rheedia gardneriana, on some of the virulence properties of Streptococcus mutans associated with biofilm development and acidogenicity. The synthesis of glucans by glucosyltransferases B (GTF B) and C (GTF C) was markedly reduced by 7-epiclusianone showing more than 80% inhibition of enzymatic activity at a concentration of 100 mgmL 1. Doublereciprocal analysis (Lineweaver–Burk plots) revealed that the inhibition of GTF B activity was noncompetitive (mixed) while GTF C was inhibited uncompetitively. The glycolytic pH drop by S. mutans cells was also disrupted by 7-epiclusianone without affecting the bacterial viability, an effect that can be attributed, in part, to inhibition of F-ATPase activity (61.1 3.0% inhibition at 100 mgmL 1). Furthermore, topical applications (1-min exposure, twice daily) of 7-epiclusianone (at 250 mgmL 1) disrupted biofilm formation and physiology. The biomass (dryweight), extracellular insoluble polysaccharide concentration and acidogenicity of the biofilms were significantly reduced by the test agent (Po0.05). The data show that 7-epiclusianone disrupts the extracellular and intracellular sugar metabolism of S. mutans, and holds promise as a novel, naturally occurring compound to prevent biofilm-related oral diseases.Item Mechanism of the vasodilator effect of Euxanthone in rat small mesenteric arteries.(2010) Câmara, Diógenes Vadim; Lemos, Virgínia Soares; Santos, Marcelo Henrique dos; Nagem, Tanus Jorge; Côrtes, Steyner de FrançaMechanism of the vasodilator effect of Euxanthone in rat small mesenteric arteries In the present work we investigated the mechanism involved in the vasodilator effect induced by euxanthone in rat small mesenteric arteries. We observed that euxanthone induced concentration dependent vasodilatation in arteries by a mechanism independent on the release of endothelial factors, such as nitric oxide (NO) and cyclooxygenase-derived factors. In addition our results also suggest that euxanthone induced its vasodilator effect through inhibition of calcium-sensitive mechanisms activated by protein kinase C, rather than by inhibition of contractions dependent on the release of the intracellular calcium stores or by inhibition of voltage-operated calcium channels.Item On the relationships between molecular conformations and intermolecular contacts toward crystal self-assembly of mono-, di-, tri-, and tetra-oxygenated xanthone derivatives.(2010) Correa, Rodrigo de Souza; Santos, Marcelo Henrique dos; Nagem, Tanus Jorge; Ellena, Javier AlcidesOxygenated xanthones have been extensively investigated over the years, but there are few reports concerning their crystal structure. Our chemical investigations of Brazilian plants resulted in the isolation of four natural products named 1-hydroxyxanthone (I), 1-hydroxy-7- methoxyxanthone (II), 1,5-dihydroxy-3-methoxyxanthone (III), and 1,7-dihydroxy-3,8-dimethoxyxanthone (IV). The structures of these compounds were established on the basis of single crystal X-ray diffraction. The xanthone nucleus conformation is essentially planar with the substituents adopting the orientations less sterically hindered. In addition, classical intermolecular hydrogen bonds (O–H O) present in III and IV give rise to infinite ribbons. However, the xanthone I does not present any intermolecular hydrogen bonds, meanwhile the xanthone II presents only a non-classical one (C–H O). The crystal packing of all xanthone structures is also stabilized by p–p interactions. The fingerprint plots, derived from the Hirshfeld surfaces, exhibited significant features of each crystal structures.Item Spectroscopic investigation of organotin (IV) derivatives of 7-epiclusianone : a preliminary in vitro antitumor evaluation of HN-5 human carcinoma cell.(2009) Vieira, Flaviana Tavares; Maia, José Roberto da Silveira; Vilela, Marcelo José; Ardisson, José Domingos; Santos, Marcelo Henrique dos; Oliveira, Tânia Toledo de; Nagem, Tanus JorgeA series of organotin(IV) compounds have been prepared by reaction with 7-epiclusianone (Epi), a natural product extracted from fruits of Rheedia gardneriana. This compound has an interesting motif with several coordinating sites for metal-ligand bond formation, and in solution, it shows a keto-enol tautomerism. The NMR of the organotin(IV) derivatives has revealed intramolecular hydrogen bonding, indicating that the keto-enol tautomerism of 7-epiclusianone is not involved upon coordination of those, but the absence of this bonding type in the case of the SnCl4 derivative suggests a strong interaction. The Mössbauer spectroscopy has revealed five- and six-fold coordination for the organotin(IV) and SnCL» derivatives in the solid state. However, in solution all tin complexes have six-fold coordination, as shown by "9Sn NMR. The overall data point out that the organotin(IV) precursors SnClxPri4_x (x = 1, 2) are weakly bonded to the 7- epiclusianone, except the SnC^. Bioassay in vitro of the substance test [SnClPh3(£/7/)] (1) has been investigated using two epithelial cells: normal MDCK from canine kidney, and IIN-5 from a human carcinoma of the tongue. The results clearly demonstrate that the time for cellular reproduction has been reduced in the presence of the substance test.Item Synthesis, activity, and docking studies of eugenol-based glucosides as new agents against Candida sp.(2018) Hipolito, Taciane Maira Magalhães; Bastos, Guilherme Tadeu Lemos; Barbosa, Thulio Wliandon Lemos; Souza, Thiago Belarmino de; Coelho, Luiz Felipe Leomil; Dias, Amanda Latercia Tranches; Rodríguez, Ihosvany Camps; Santos, Marcelo Henrique dos; Dias, Danielle Ferreira; Franco, Lucas Lopardi; Carvalho, Diogo TeixeiraSeventeen new synthetic derivatives of eugenol (6, 8–15 and 8′‐15′) were planned following literature reports on antifungal activities of nitroeugenol and eugenol glucoside. The anti‐Candida activity of these compounds was investigated by in vitro assay, and the cytotoxicity evaluation was performed with the most active compounds. The peracetylated glucosides presented better biological results than their hydroxylated analogues. The glucoside 11, a 4‐nitrobenzamide, showed the best potency (MIC50 range 11.0–151.84 μm), the wider spectrum of action, and overall the best selectivity indexes, especially against C. tropicalis (~30) and C. krusei (~15). To investigate its possible mechanism of action, glucoside 11 was subjected to molecular docking studies with Candida sp. enzymes involved in ergosterol biosynthesis. Results have shown that the peracetyl glucosyl moiety and the 4‐nitrobenzamide group in 11 are effectively involved in its high affinity with the active site of squalene epoxidase.Item Total assignment of 1H and 13C NMR spectra of a prenylated oxanthrone from Vismia latifolia.(2000) Santos, Marcelo Henrique dos; Nagem, Tanus Jorge; Silva, L. G. F. e; Silva, Marilda Conceição daNew prenylated oxanthrones, vismianol A and vismianol B [(1,3,8,10-tetrahydroxy-6-methyl-4,5-bis(3- methylbut-2-enyl)anthracen-9(10H)-one) (3a and 3c)] were isolated from the roots of Vismia latifolia (Clusiaceae) as a mixture of two enantiomers, in addition to two other known anthraquinones (chrisophanol and physcion). The structures were established by 2D NMR spectroscopic techniques (HMQC, HMBC and NOESY).Item Total assignment of 1H and 13C NMR spectra of two 3,4-secofriedelanes from Austroplenckia populnea.(2001) Vieira Filho, Sidney Augusto; Duarte, Lucienir Pains; Silva, Grácia Divina de Fátima; Lula, Ivana Silva; Santos, Marcelo Henrique dosTwo new 3,4-secofriedelanes, 3,4-seco-28-hydroxyfriedelan-3-oic acid (1) and 3,4-secofriedelan-3-oic acid (2),were isolated from the leaves of Austroplenckia populnea (Celastraceae).The structureswere established by 2D NMR spectroscopic techniques (COSY, HMQC, HMBC and NOESY).Item Vascular effects of 7-epiclusianone, a prenylated benzophenone from Rheedia gardneriana, on the rat aorta.(2006) Cruz, Allan Jefferson; Santos, Marcelo Henrique dos; Nagem, Tanus Jorge; Côrtes, Steyner de FrançaThe vascular effects of 7-epiclusianone on the rat aorta were investigated. In the rat aortic rings with functional endothelia, 7-epiclusianone up to 10mM induced a concentration-dependent vasodilatation of the sustained con tractions induced by phenylephrine (0.3mM). At concentrations higher than 10mM, 7-epiclusianone induced a concentration-dependent contraction in the aortic rings . The vasodilator effect of 7 -epiclusianone was drastically decreased with L-NAME (100m M) as well as in endothelium-denuded aortic rings. Moreover, indo methacin (10mM) induced a significant shift to the left in the vasodilator but did not modify the vasoconstrictor effect of 7-epiclusianone. In arteries without pre-contraction, 7-epi clusianone (3–100 m M) induced concentration-dependent contraction only in endothelium- intact an d in the presence of L-NAM E (100 m M). This effect was inhibited by indomet hacin (10mM ) and ZM2 30487 (1 mM), selective inhibitors of cyclooxygenase and of 5-lipoxygenase, respectively. We can conclude that at low concentrations 7 -epiclusianone induces an endothelium-dependent vasodilator effect in rat aortic rings . At higher concentrations an d in conditions where NO synthase was inhibited, 7-epiclusianone induces a vasocontractile effect. Nitric oxide seems to participate in the vasodilatation , while endothelial cyclooxygenase and 5 -lipoxygenase-derived products play a role in the vasoconstrictor effect.