Orientadores: Pedro Paulo Corbi, André Luiz Barboza Formiga / Tese (doutorado) - Universidade Estadual de Campinas, Instituto de Química / Made available in DSpace on 2018-08-27T06:22:14Z (GMT). No. of bitstreams: 1 Carvalho_MarcosAlbertode_D.pdf: 4861042 bytes, checksum: 806502263c8b6f3d1f87f5ac3834609c (MD5) Previous issue date: 2015 / Resumo: O uso de metais em medicina, no tratamento de doenças, data desde a antiguidade. Sais de prata são utilizados há séculos como agentes antimicrobianos, enquanto que, mais recentemente, complexos de Au(I) e Pt(II) tem sido pesquisados e utilizados como agentes antiartríticos e antitumorais, respectivamente. Nesta Tese, são apresentados estudos de síntese, caracterização estrutural e ensaios biológicos in vitro de novos complexos metálicos de Pt(II), Pd(II), Ag(I) e Au(III) com diferentes ligantes bioativos: triptofano (Trp), triptamina (tra), ácido mefenâmico (mef) e carnosina (car). Os complexos foram preparados a partir da reação em solução aquosa ou alcoólica dos ligantes e dos respectivos sais metálicos. As composições dos complexos foram determinadas por análise elementar, espectrometria de massas e por análise termogravimétrica. Estudos espectroscópicos e de modelagem molecular permitiram propor os modos de coordenação dos ligantes aos íons metálicos. Os complexos de Ag(I) e Pd(II) com Trp mostraram atividade sobre cepas bacterianas Gram-negativas e Gram-positivas. O complexo de Pd(II) com triptamina não apresentou atividade frente as cepas de Escherichia coli, Pseudomonas aeruginosa e Staphylococcus aureus. O complexo de Pd(II) com ácido mefenâmico e bipiridina mostrou atividade inibitória frente a cepas de S. aureus e não foi ativo sobre E. coli e P. aeruginosa. Estudos de citotoxicidade dos complexos de Ag(I), Pd(II) e Pt(II) com Trp pela redução do MTT sobre as linhagens de células Balb/c3T3, SK-Mel 103 e Panc-1 mostraram que os complexos são citotóxicos para todas as linhagens consideradas / Abstract: The use of metals in medicine in the treatment of diseases dates since antiquity. Silver salts have been used as antimicrobial agents for centuries, while more recently, Au(I) and Pt(II) complexes have been investigated and used as antiarthritic and antitumor agents, respectively. This Thesis presents the synthesis, structural characterization and biological assays in vitro of new metal complexes of Ag(I), Pd(II), Pt(II) and Au(III) with the bioactive ligands tryptophan (Trp), tryptamine (tra), mefenamic acid (mef) and carnosine (car). The complexes were prepared by the reaction of the ligands and metal salts in aqueous or alcoholic solutions. Composition of complexes were determined by elemental analysis, mass spectrometry and thermogravimetric analyses. Spectroscopic and molecular modeling studies were used to determine the coordination modes of the ligands to the metals. Complexes of Ag(I) and Pd(II) with Trp showed activity against Gram-positive and Gram-negative strains. The Pd(II) complex with tryptamine showed no activity against Escherichia coli, Pseudomonas aeruginosa ande Staphylococcus aureus strains. The Pd(II) complex with mefenamic acid and bipyridine showed inhibitory activity against S. aureus strains and it was not active on E. coli and P. aeruginosa. Cytotoxicity studies of the Ag(I), Pd(II) and Pt(II) complexes with Trp by MTT reduction on Balb/c3T3, SK-Mel 103 and Panc-1 lines cells showed that complexes are cytotoxic to all considered cells / Doutorado / Quimica Inorganica / Doutor em Ciências

Les travaux décrits dans ce manuscrit concernent l’élaboration de conservateurs naturels et hydrosolubles à base de polysaccharides greffés par des molécules actives d’origine végétale de type phénoliques (peu solubles dans l’eau). L’objectif est de développer de nouveaux systèmes présentant des propriétés antioxydantes et/ou antibactériennes, voire rhéologiques et principalement destinés aux domaines des formulations aqueuses cosmétiques et/ou alimentaires. Pour ce faire, le composé aminogaïacol (dérivé du gaïacol) a été greffé chimiquement sur un polysaccharide (carboxyméthylpullulane) selon des proportions variées (comprises entre 5 et 58 %). Les études physico-chimiques en milieux salins dilué et semi-dilué mettent en avant un caractère associatif (de type polysavon) des dérivés les plus greffés, avec des interactions intramoléculaires hydrophobes prédominantes qui limitent les propriétés rhéologiques. Tous les produits synthétisés ont par contre démontré des propriétés antioxydantes et antibactériennes. Le caractère associatif (i.e. la présence de microdomaines hydrophobes) s’est avéré être favorable à l’activité antioxydante, avec les meilleures activités observées pour le dérivé le plus fortement greffé en aminogaïacol (58%). Au contraire, le comportement associatif a limité l’activité biologique, dans ce cas, c’est le dérivé le moins greffé (5%) qui a démontré la meilleure activité antibactérienne, en raison d’une meilleure disponibilité des greffons. Afin d’améliorer les propriétés biologiques et/ou rhéologiques, cette approche de greffage de l’aminogaïacol a été étendue sur un autre polysaccharide anionique (l’alginate), plus rigide que le carboxyméthylpullulane avec des résultats prometteurs notamment en rhéologie. / The works described in this manuscript concern the development of natural and water soluble preservatives based on polysaccharides grafted with molecules of plant origin (from phenolic structure). The aim consists in developing new systems with antioxidant and/or antibacterial properties together with rheological ones for cosmetic and/or food application fields. For this purpose, aminoguaiacol (derived from guaiacol) was chemically grafted onto a polysaccharide (carboxymethylpullulan) in various proportions (between 5 and 58 %). The physicochemical studies in dilute and semi-dilute saline media put forward an associative character (of polysoap type) of the most grafted derivatives, with predominant hydrophobic intramolecular interactions which are limiting for rheology. All synthesized products have demonstrated antioxidant and antibacterial properties. The associative character (i.e., the presence of hydrophobic microdomains) was found to be favorable to the antioxidant activity, with the best activity for the most grafted aminoguaiacol derivative (58%). On the contrary, the associative behavior limited the antibacterial activity, in this case, the least grafted derivative (5%) demonstrated the best antibacterial activity, due to best availability of the grafted moieties. In order to improve the biological and/or rheological properties, this grafting approach of aminoguaiacol has been extended to another anionic polysaccharide (alginate), more rigid than carboxymethylpullulan with promising results notably as concerns rheology.

No description available.

Indiana University-Purdue University Indianapolis (IUPUI) / The furanone derivatives and their constructed polymers were synthesized, characterized and formulated into dental glass-ionomer cement (GIC) and resin composite for improved antibacterial properties. Compressive strength (CS) and S. mutans viability were used to evaluate the mechanical strength and antibacterial activity of the restoratives. Fuji II LC cement and P60 were used as control. The specimens were conditioned in distilled water at 37 oC for 24 h prior to testing. The effects of loading, saliva and aging on CS and S. mutans viability were investigated. The antibacterial effect of the furanone derivative on other bacteria was also studied. Chapter 2 describes how we studied and evaluated the formulated antibacterial glass-ionomer cement by incorporating the synthesized furanone derivative-containing polymer into the formulation. The results show that all the formulated furanone-containing cements showed a significant antibacterial activity, accompanying with an initial CS reduction. Increasing loading significantly enhanced antibacterial activity but reduced the initial CS of the formed cements. The derivative showed a broad antibacterial spectrum on bacteria including S. mutans, lactobacillus, S. aureus and S. epidermidis. Human saliva did not affect the antibacterial activity of the cement. The long-term aging study indicates that the cements may have a long-lasting antibacterial function. Chapter 3 describes how we studied and evaluated the formulated antibacterial resin composite by incorporating the synthesized furanone derivative into the basic resin formulations. The results show that the modified resin composites showed a significant antibacterial activity without substantially decreasing the mechanical strengths. With 5 to 30% addition of the furanone derivative, the composite kept its original CS unchanged but showed a significant antibacterial activity with a 16-68% reduction in the S. mutans viability. Further, the antibacterial function of the new composite was not affected by human saliva. The aging study indicates that the composite may have a long-lasting antibacterial function. In summary, we have developed a novel furanone-containing antibacterial system for dental restoratives. Both glass-ionomer cement and resin composite have demonstrated significant antibacterial activities. The modified experimental glass-ionomer cement is a promising system because the reduced strength of the cement with addition of the furanone-containing polymer is still above those demonstrated by original commercial cement Fuji II LC. The modified resin composite shows nearly no reduction in mechanical strength after incorporation of the antibacterial furanone derivative. It appears that both experimental cement and resin composite are clinically attractive dental restoratives that can be potentially used for long-lasting restorations due to their high mechanical strength and permanent antibacterial function.

Susceptibility of 112 strains of Staphylococcus aureus obtained from Dameron Hospital, Stockton, California was tested with 18 antimicrobials . The MIC method was used with the following antimicrobials : tetracycline, oxacillin, penicillin, ampicillin, vancomycin, cefazolin, erythromycin, clindamycin, gentamycin, rifampin, trimethoprimsulfamethoxazole, chloramphenicol, and cefotaxime . The standard Kirby-Bauer disc diffusion method was used to test neomycin, tobramycin, and amikacin . Methicillin, oxacillin, and nafcillin were tested with a modified Kirby-Bauer method, which included the addition of a 4% salt supplement to the media, incubation at 32C, and readings at both 24 and 48 hours. Comparing results of this study with those of Hall (1975), suggested that resistance to the following antibiotics has increased: penicillin, ampicillin, erythromycin, neomycin, gentamycin, methicillin, oxacillin, nafcillin, cefazolin, and clindamycin . Resistance to tetracycline has decreased. No resistance to chloramphenicol or vancomycin was encountered in either study . Of the 112 strains studied, 13 . 4% were susceptible to all antibiotics tested. Twelve patterns of resistance were identified : 0 . 9% were resistant to neomycin only, 1.8% to erythromycin only, 63.9% to both penicillin and ampicillin, and 20 . 0% were multiply- resistant . Nine patterns of multiple-resistance were found, involving a minimum of three antibiotics and a maximum of nine . Three MRSA strains were identified from out-patient isolates; no in-patient isolates were methicillin-resistant . The study suggests that MRSA strains are not a problem at Dameron Hospital, but identification of this group would be more accurate if incubation of the MIC panels is maintained for at least 24 hours at ~35C . It was found that the MIC method of antimicrobial susceptibility testing is more reliable than the Kirby-Bauer disc diffusion method for detection of methicillin-resistance. Problems involved in identification of heteroresistant staphylococci are discussed .

With antimicrobial resistance to current drugs steadily rising, the development of new antibiotics with novel mechanisms of action has become an imperative. The majority of life-threatening infections worldwide are caused by "ESKAPE" pathogens which are encountered in more than 40% of hospital-acquired infections, and are resistant to the majority of commonly used antibiotics. Naturally occurring cyclic depsipeptides, microbial secondary metabolites that contain one or more ester bonds in addition to amide bonds, have emerged as an important source of pharmacologically active compounds or lead structures for the development of novel antibiotics. Some of those peptides are either already marketed (daptomycin) or in advanced stages of clinical development (ramoplanin). Structurally simple, yet potent, fusaricidin/LI-F and lysobactin families of naturally occurring antibiotics represent particularly attractive candidates for the development of new antibacterial agents capable of overco ming infections caused by multidrug-resistant bacteria. These natural products exhibit potent antimicrobial activity against a variety of clinically relevant fungi and Gram-positive bacteria. Therefore, access to these classes of natural products and their synthetic analogs, combined with elucidation of their mode of action represent important initial steps toward full exploitation of their antmicrobial potential. This dissertation describes a general approach toward the solid-phase synthesis of fusaricidin/LI-F and lysobactin analogs and an extensive structure-activity relationship (SAR) study. We have devised a simple and robust preparation strategy based on standard Fmoc solid-phase peptide synthesis protocols. / The SAR study revealed key structural requirements for fusaricidin/LI-F and related cyclic lipopeptides antibacterial activity, including the presence of the guanidino moietly at the end of the lipidic tail, hydrophobic amino acid residues, and peptide conformation Moreover, substitution of the ester bond with an amide bond significantly improved stability under physiologically relevant conditions and reduced toxicity. In addition, we have shown that these antibacterial peptides exert their mode of action via a novel mechanism, which invloves bacterial membrane interactions, followed by peptide internalization. Altogether, the research described in this dissertation demonstrates that new antibiotics derived from fusaricidin/LI-F natural products, have the potential to meet the challenge of antibiotic resistance in Gram-positive bacteria. / by Nina Bionda. / Thesis (Ph.D.)--Florida Atlantic University, 2013. / Includes bibliography. / Mode of access: World Wide Web. / System requirements: Adobe Reader.

FundaÃÃo Cearense de Apoio ao Desenvolvimento Cientifico e TecnolÃgico / Os sistemas adesivos atuais apresentam resultados satisfatÃrios no que concerne à adesÃo ao esmalte e à dentina, entretanto, a maior causa de falhas em restauraÃÃes estÃticas ainda à a ocorrÃncia de recidiva de cÃrie ao longo de suas margens. Desta forma, este estudo avaliou a aÃÃo de sistemas adesivos com flÃor e/ou com um novo monÃmero, brometo de metacriloiloxidodecilpiridinio (MDPB) na composiÃÃo microbiolÃgica do biofilme dental e no processo de desmineralizaÃÃo do esmalte adjacente à restauraÃÃo de resina composta, mediante um delineamento in situ, cruzado e duplo-cego. Durante duas fases de 14 dias, dez voluntÃrios utilizaram dispositivos palatinos, contendo, cada um, quatro blocos de esmalte dental humano, restaurados extra-oralmente com resina composta Z250 e um dos seguintes sistemas adesivos: Adperâ Single Bond 2 (condicionamento total, G1), All-Bond SEâ (autocondicionante, G2), One-Up Bond F Plus (autocondicionante com flÃor, G3) e Clearfil Protect Bond (autocondicionante com flÃor e MDPB, G4). Os voluntÃrios foram aleatoriamente divididos entre os grupos, sendo que os que receberam os sistemas adesivos referentes aos grupos G1 e G2, na 1 fase, receberam os tratamentos referentes aos grupos G3 e G4 na 2 fase e vice-versa. Todos os voluntÃrios foram instruÃdos a gotejar sobre os blocos, oito vezes por dia, uma soluÃÃo de sacarose a 20%, simulando um desafio cariogÃnico, e a utilizar um dentifrÃcio fluoretado padronizado trÃs vezes por dia na higienizaÃÃo dentÃria. ApÃs o tÃrmino de cada fase o biofilme formado sobre cada bloco foi coletado e utilizado para a contagem de estreptococos totais, estreptococos mutans e lactobacilos. A perda de mineral foi analisada por meio do teste de microdureza em corte longitudinal do esmalte adjacente à restauraÃÃo. Aplicou-se a anÃlise de variÃncia, ANOVA, nÃo sendo observada diferenÃa estatisticamente significante para a composiÃÃo microbiolÃgica ou desmineralizaÃÃo do esmalte entre os adesivos estudados. Concluiu-se que a incorporaÃÃo de MDPB e/ou flÃor nos sistemas adesivos autocondicionantes nÃo foi capaz, nas condiÃÃes deste estudo, de prevenir a ocorrÃncia da cÃrie secundÃria. / Contemporary adhesives systems present satisfactory bonding to enamel and dentin. However, replacement of the restorations due to secondary caries formation is still a major problem and of great concern in Dentistry. Thus, this study assessed in situ the effects of adhesive systems containing or not fluoride and/or the antibacterial monomer 12-methacryloyloxydodecylpyridinium bromide (MDPB) on the microbiological composition of dental biofilm and on enamel demineralization. During two phases of 14 days each, ten volunteers wore palatal appliances containing four human enamel slabs, which were extra-orally restored using a resin composite (Z250 3M-ESPE) and one of the following adhesive systems: Adperâ Single Bond 2 (total etch, G1); All-Bond SEâ (self-etch, G2); One-Up Bond F Plus (self-etch containing fluoride G3) and Clearfil Protect Bond (self-etch containing fluoride and MDPB, G4). The volunteers were randomly allocated to treatments, and those who received G1 and G2 in the first phase received G3 and G4 in the second one, and vice versa. The volunteers were asked to drop a 20% sucrose solution onto the slabs eight times per day and to use fluoridated dentifrice 3 times per day. The biofilm formed on the slabs was analyzed with regard to total and mutans streptococci as well as lactobacilli counts. Demineralization was determined on enamel around the restorations by cross-sectional microhardness. The data were analyzed by analysis of variance, ANOVA. No differences were found for microbiological composition or enamel demineralization among the studied adhesive systems. It can be concluded that that fluoride or MDPB addition to adhesives systems presented no effect in controlling caries around resin restorations in this in situ model.

Thesis (MSc. (Microbiology)) -- University of Limpopo, 2017 / This study was aimed at isolating and evaluating the antibacterial, antioxidant and cytotoxic effects of active compounds from selected medicinal plant species. The biological activities and cytotoxic effects of Commelina africana, Dombeya rotundifolia, Elephantorrhiza elephantina and Schkuhria pinnata were investigated based on their traditional uses. The plants were extracted with different solvents of varying polarities. Methanol was the best extractant with the highest yield. The presence of different phytoconstituents was screened using standard methods; this revealed the presence of terpenoids, flavonoids, tannins, and saponins. Meanwhile, the phytochemicals were screened on TLC, where different colours observed indicated the presence of different compounds. The total phenolic, tannin and flavonoid content were estimated using spectrophotometric methods. D. rotundifolia had the highest amounts of phenol, tannin and flavonoid content, while S. pinnata had the least. The antibacterial and antioxidant screening employed both qualitative and quantitative assays. Although not separated, this study demonstrated the antioxidant potential of D. rotundifolia extracts developed in BEA and CEF. D. rotundifolia also demonstrated the highest free radical scavenging and reducing power antioxidant potential. These activities could be attributed to the high phenolic, tannin and flavonoid content observed. All the selected plants had antibacterial potential against E. coli and P. aeruginosa. Only S. pinnata extracts were active against E. faecalis and S. aureus. The MIC values of the plants and ampicillin ranged from 0.02 to 2.50 mg/mL and 0.02 to 0.08 mg/mL, respectively. The plants were combined to determine any interaction effects in exhibiting antibacterial activity. Among all the possible combinations, combinations with S. pinnata had improved antibacterial activity. The effects of D. rotundifolia and S. pinnata extracts on the inhibition of the production of reactive oxygen species on LPS-induced RAW 264.7 macrophages was determined using the DCFHD-A assay. Both plants demonstrated anti-inflammatory potential by inhibiting the production of ROS in a dose-dependent manner. Cell viability assays revealed that S. pinnata had cytotoxic effects on African green monkey kidney (Vero) cells with the lowest LC50 (25 µg/mL). Bioassay guided fractionation and nuclear magnetic resonance spectroscopy of dichloromethane extracts of S. pinnata on column chromatography afforded isolation and characterisation of three sesquiterpene lactones. These were identified as 6-(2, 3- xxvi dihydroangeloylory)-6α-hydroxyinuviscolide, heliangolide and eucannabiolide. All three compounds had antibacterial, anti-inflammatory and cytotoxic effects. The compounds may serve as leads for synthesis of less toxic therapeutic antibacterial and anti-inflammatory drugs in the pharmaceutical industry. / National Research Foundation (NRF)

Diss. (sammanfattning) Stockholm : Karol. inst., 2004. / Härtill 6 uppsatser.

Orientador: Reginaldo Bruno Gonçalves / Tese (doutorado) - Universidade Estadual de Campinas, Faculdade de Odontologia de Piracicaba / Made available in DSpace on 2018-08-08T12:34:48Z (GMT). No. of bitstreams: 1 Kamiya_RegianneUmeko_D.pdf: 1901318 bytes, checksum: 6b54c1e6cbe9e4b6b6fb94ea27db2ec2 (MD5) Previous issue date: 2006 / Resumo: Esta tese, apresentada na forma de 3 artigos, teve por objetivos: (1) analisar a freqüência dos genes de produção de mutacinas I, II, III e IV, em genótipos de S. mutans isolados de indivíduos cárie-ativos e livres de cárie, (2) analisar a freqüência dos genes de produção das mutacinas I, II, III, IV, N, B-Ny 266, 1140 e genes homólogos às bacteriocinas, identificadas em outras espécies bacterianas, em cepas de S. mutans isolados de crianças, bem como detectar a expressão diferencial dos genes identificados, em células de S. mutans crescidas na condição planctônica e séssil, (3) analisar a expressão dos genes de produção das mutacinas I, II e proteínas kinases CiaH, Dgk e ComD, em diferentes fases do crescimento planctônico e séssil. O rastreamento e a freqüência dos genes estruturais de diferentes mutacinas em isolados de S. mutans, foram realizados pela técnica de PCR e a análise da expressão gênica, pela técnica de RT-PCR semi-quantitativa. Os estudos, apresentados nesta tese, demonstraram o papel das mutacinas como um fator de virulência, altamente diversificado entre a espécie S. mutans, e relacionado com o risco de cárie. Este fator de virulência, pode ser regulado por mecanismos quorum-sensing, sendo assim, dependente da condição de crescimento planctônica ou séssil. A regulação da produção de mutacinas, por mecanismos quorum-sensing, pode representar uma vantagem seletiva à espécie produtora, principalmente em ambiente complexo, como o biofilme dental e lesões de cárie. Futuramente, mais estudos serão necessários para identificar novos determinantes genéticos, necessários para a síntese de substâncias semelhantes às mutacinas, bem como, identificar os mecanismos e componentes, que modulam a expressão deste importante fatorde virulência em S. mutans / Abstract: This thesis, comprised of 3 manuscripts was designed (1) to analyse the frequency of biosynthesis genes of the mutacins types I, II, III and IV, in S. mutans isolated from caries-affected and caries-free individuals, (2) to analyse the frequency of biosynthesis genes of the mutacins types I, II, III, IV, N, B-Ny 266, 1140 and genes homologues to bacteriocins identified in other bacterial species, in S. mutans isolated from children, in addition, to detect the differential expression of these genes, in S. mutans cells grown in planktonic and sessil conditions, (3) and to analyse the expression of the mutacins I and II production genes and kinase proteins genes (ciaH, dgk e comD), in different phases of the planktonic and sessile growth. The screening and frequency of the mutacins structural genes in S. mutans isolates were realized by PCR technique and the analysis of genetic expression, by RT-PCR semiquantitative method. The studies, presented in this thesis, demonstrate the role of mutacins as a virulence factor, highly diverse among S. mutans, and related to risk of dental caries. The mutacins production may be regulated by quorum-sensing mechanisms and is dependent on planktonic and sessile conditions. The modulation by quorum-sensing mechanisms may represent a selective advantage for producer S. mutans strain, mainly in complex environments as the dental biofilm and caries. Hereafter, more studies will be necessary to identify new genetic determinants for synthesis of mutacin-like substances and elucidate the mechanisms and components that modulate the genetic expression of this important virulence factor in S. mutans / Doutorado / Microbiologia e Imunologia / Doutor em Biologia Buco-Dental