Submitted by Sandra Pereira (srpereira@ufrrj.br) on 2017-03-17T12:18:44Z No. of bitstreams: 1 2016 - Emanoel Hottes.pdf: 4033048 bytes, checksum: fe0f804a0e5a67c894370834c0964ff8 (MD5) / Made available in DSpace on 2017-03-17T12:18:44Z (GMT). No. of bitstreams: 1 2016 - Emanoel Hottes.pdf: 4033048 bytes, checksum: fe0f804a0e5a67c894370834c0964ff8 (MD5) Previous issue date: 2016-04-07 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico - CNPq / CuII complexes containing thiazole and thioimidazole derivatives have been synthesized and characterized. The ligands (E)-2-(2-benzylidenehydrazinyl)-4-phenylthiazole (L1), (E)-2-(2-(4-chlorobenzylidene)hydrazinyl)-4-phenylthiazole (L2), (E)-2-(2-(4-methoxybenzylidene)hydrazinyl)-4-phenylthiazole (L3), (E)-4-phenyl-2-(2-(pyridin-2-ylmethylene)hydrazinyl)thiazole (L4), (E)-5-phenyl-1-(pyridin-2-ylmethyleneamino)-1H-imidazole-2(3H)-thione (L5) and (E)-1-(2-hydroxybenzylideneamino)-5-phenyl-1H-imidazole-2(3H)-thione (L6), reported in the literature, have been obtained in collaboration with Laboratory LaDMol-QM from UFRRJ. For these ligands, it is been performed qualitative calculations and molecular modeling by the semi empiric method PM6 for geometry optimization and estimate the relative energies of the frontier orbitals and conformers. The crystalline structure of the ligand L2 was determined by X-ray diffraction analysis. The CuII complexes have been obtained from the reactions of the ligands with CuCl2 in different stoichiometries. The proposed structures of the complexes have been formulated based on elemental analysis of CHN, electronic paramagnetic resonance (EPR) and electronic (UV-Vis) and vibrational (FTIR) spectroscopy. The results of EPR point to the occurrence of more than one CuII nucleus in all reaction products. For complexes CuL1-CuL3 with potentially bidentate ligands it has been proposed coordination from sulfur or nitrogen from thiazole ring and nitrogen from azomethine, with possible octahedral and/or square planar geometries. For CuL4-CuL6 with potentially tridentate ligands it is been proposed coordination from sulfur as well as nitrogen atoms. For CuL6, there is also a possibility of coordination through the oxygen atom, with a CuII possibly pentacoordinate.. Studies with yeast have shown that amongst the compounds, L1 has had the best activity in the inhibition of the cell growth. It was possible to observe that all compounds decrease the cell survival during the period of incubation. The studies of lipid peroxidation have shown that the complexes were more toxic than the ligands and the complex CuL3 has shown better toxicity when compared to the other compounds and the control. / Complexos de CuII com ligantes derivados de tiazol e tioimidazol, foram sintetizados e caracterizados. Os ligantes (E)-2-(2-benzilidenohidrazinil)-4-feniltiazol (L1), (E)-2-(2-(4-clorobenzilideno)hidrazinil)-4-feniltiazol (L2), (E)-2-(2-(4-metoxibenzilideno)hidrazinil)-4-feniltiazol (L3), (E)-4-fenil-2-(2-(piridin-2-il-metileno)hidrazinil)tiazol (L4), (E)-5-fenil-1-((piridin-2-il-metileno)amino)-1H-imidazol-2(3H)-tiona (L5) e (E)-1-((2-hidroxibenzilideno)amino)-5-fenil-1H-imidazol-2(3H)-tione (L6), j? reportados na literatura, foram obtidos e caracterizados em parceria com o Laborat?rio LaDMol-QM da UFRRJ. Para estes ligantes foram realizados c?lculos qualitativos de modelagem molecular pelo m?todo semi-emp?rico PM6 para otimiza??o de geometria e estimativas de energias relativas de orbitais de fronteira e de conf?rmeros. A estrutura cristalina do ligante L2 foi determinada por difra??o de raios-X de monocristal. Os complexos de CuII foram obtidos a partir de rea??o dos ligantes com CuCl2 em diferentes estequiometrias. As propostas para os complexos foram formuladas com base nos dados de an?lise elementar de CHN, resson?ncia paramagn?tica eletr?nica (EPR) e espectroscopias eletr?nica (UV-vis) e vibracional (FTIR). Os resultados de EPR apontam para a ocorr?ncia de mais de um n?cleo de CuII em todos os produtos. Para os complexos CuL1-CuL3 com ligantes potencialmente bidentados (L1-L3) foi proposta complexa??o tanto pelo ?tomo de enxofre (anel tiazol) como tamb?m pelos ?tomos de nitrog?nio (azometino), com possibilidades de geometrias octa?dricas e tamb?m quadradas. J? os complexos CuL4-CuL6, com ligantes potencialmente tridentados (L4-L6), foi proposta complexa??o tanto pelo ?tomo de enxofre do anel tiazol como tamb?m pelos ?tomos de nitrog?nio do azometino e do anel pirid?nico. No caso de CuL6 ainda h? possibilidade de coordena??o atrav?s do ?tomo de oxig?nio, com CuII possivelmente pentacoordenado.. Testes realizados em leveduras mostraram que dentre os compostos, o L1 foi o que apresentou melhor desempenho na inibi??o do crescimento das c?lulas. No caso do teste de viabilidade foi poss?vel observar que todos os compostos diminuem a sobrevida celular no per?odo de incuba??o. Por meio da an?lise de peroxida??o lip?dica foi poss?vel verificar que os complexos foram mais t?xicos do que os ligantes e que o CuL3 foi o que apresentou maior toxidez quando comparado com os demais complexos e com o controle

Submitted by Automa??o e Estat?stica (sst@bczm.ufrn.br) on 2017-06-02T23:22:49Z No. of bitstreams: 1 ItaloDiegoReboucasDeAraujo_DISSERT.pdf: 1921634 bytes, checksum: f5b0152026c412caa425bbe005935152 (MD5) / Approved for entry into archive by Arlan Eloi Leite Silva (eloihistoriador@yahoo.com.br) on 2017-06-12T21:29:47Z (GMT) No. of bitstreams: 1 ItaloDiegoReboucasDeAraujo_DISSERT.pdf: 1921634 bytes, checksum: f5b0152026c412caa425bbe005935152 (MD5) / Made available in DSpace on 2017-06-12T21:29:47Z (GMT). No. of bitstreams: 1 ItaloDiegoReboucasDeAraujo_DISSERT.pdf: 1921634 bytes, checksum: f5b0152026c412caa425bbe005935152 (MD5) Previous issue date: 2017-01-30 / Atualmente, v?m intensificando-se os estudos na ?rea de qu?mica medicinal com intuito de elucidar novos fitof?rmacos, seja atrav?s da obten??o de extratos, fra??es, compostos isolados ou ?leos essenciais que apresentem algum tipo de atividade biol?gica. Neste contexto, destaca-se a aroeira-do-sert?o (Myracrodruon urundeuva), da fam?lia Anacardiaceae, j? estudada quanto ao potencial antimicrobiano, anti-inflamat?rio e cicatrizante. Motivado por novas alternativas terap?uticas, considerando a crescente resist?ncia microbiana, esse estudo avaliou a atividade antimicrobiana de produtos naturais obtidos das folhas da referida planta. Dentre estes est? um ?leo essencial, que foi extra?do por hidrodestila??o, caracterizado por RMN e GC-MS, e avaliado quanto ? citotoxicidade, al?m de extratos org?nicos, que foram analisados quanto ? atividade antimicrobiana: metan?lico liofilizado, obtido por decoc??o; clorof?rmico e acetato de etila, extra?dos ? temperatura ambiente com seus respectivos solventes e filtrados sob press?o reduzida. A atividade antibacteriana foi avaliada pela t?cnica da microdilui??o em caldo, na qual as CIMs foram determinadas utilizando CTT (cloreto de 2,3,5-trifenil-tetrazolium) como revelador do crescimento bacteriano, e as CBMs por meio da an?lise do crescimento do conte?do dos po?os em ?gar BHI. A citotoxicidade do ?leo foi avaliada pelo m?todo do MTT, brometo de 3-(4,5-dimetiltiazol-2-il)-2,5-difenil tetraz?lio. O ?leo, na caracteriza??o qu?mica, dentre os terpenos identificados, apresentou como constituinte majorit?rio o ?-pineno (87,85%). Al?m disso, tal ?leo mostrou atividade antibacteriana frente a todas as cepas testadas, onde para algumas destas ocorreu equival?ncia entre os valores de CIM e CBM, que foram de 0,22 mg/mL para Staphylococcus aureus, 0,44 mg/mL para Salmonella Enteritidis e 7 mg/mL para Pseudomonas aeruginosa. J? para Staphylococcus epidermidis a CIM foi 0,11 mg/mL e a CBM 0,22 mg/mL. Escherichia coli foi inibida com CIM de 0,88 mg/mL e CBM de 1,75 mg/mL. Equival?ncia entre CIM e CBM foi observada para extrato metan?lico frente a S. epidermidis (9,75 mg/mL). Para S. aureus, a CIM deste extrato foi de 9,75 mg/mL e a CBM 78 mg/mL. Foram resistentes a tal extrato: E. coli, S. Enteritidis e P. aeruginosa. Os extratos clorof?rmico e acetato de etila foram bacteriost?ticos frente ?s cinco cepas, por?m, o clorof?rmico inibiu todas estas com CIM de 15 mg/mL, enquanto o acetato de etila apresentou CIMs de 7,56 mg/mL para S. aureus, 1,89 mg/mL para S. epidermidis, 15,12 mg/mL para S. Enteritidis e 30,25 mg/mL tanto para E. coli quanto para P. aeruginosa. Quanto ? citotoxicidade, o ?leo essencial comprometeu a viabilidade celular da linhagem Vero E6, apenas na maior concentra??o, 4,4 mg/mL, inibindo cerca de 93,91% em 24h e 94,26% em 48h. Nas c?lulas HeLa, em 24h o ?leo nessa mesma dose, teve inibi??o de 21%, que ap?s 48h aumentou para 44,3%, mostrando poss?vel a??o antitumoral. Para a linhagem de c?lulas n?o tumorais HEK-293, o ?leo n?o exerceu efeito t?xico sobre as mesmas. Conclui-se que os resultados s?o promissores, abrindo perspectivas futuras dos produtos das folhas de M. urundeuva serem farmacologicamente vi?veis. / Nowadays, studies in the field of medicinal chemistry have been intensified to elucidate new phytopharmaceuticals, by either obtaining extracts, fractions, isolated compounds or essential oils that present some type of biological activity. In this context, stands out the aroeira-do-sert?o (Myracrodruon urundeuva), of the family Anacardiaceae, studied regarding the antimicrobial, anti-inflammatory and cicatrizant potential. Motivated by new therapeutic alternatives, considering the growing microbial resistance, this study evaluated the antimicrobial activity of natural products obtained from the leaves of said plant. Among these is an essential oil, which was extracted by hydrodistillation, characterized by NMR and GC-MS, and evaluated for cytotoxicity, in addition, organic extracts, which were analyzed for antimicrobial activity: lyophilized methanolic obtained by decoction; Chloroform and ethyl acetate, extracted at room temperature with their respective solvents and filtered under reduced pressure. The antibacterial activity was evaluated by the microdilution technique in broth, in which the MICs were determined using CTT (2,3,5-triphenyl-tetrazolium chloride) as a bacterial growth promoter, and the CBMs were analyzed by growth analysis of the contents of wells on BHI agar. The cytotoxicity of the oil was evaluated by the MTT method, 3- (4,5-dimethylthiazol-2-yl) -2,5-diphenyl tetrazolium bromide. The oil had as main constituent the ?-pinene (87.85%) among the terpenes identified in the chemical characterization. In addition, this oil showed antibacterial activity against all strains tested, where for some of these, equivalence between MIC and MBC values, which were 0.22 mg/mL for Staphylococcus aureus, 0.44 mg/mL for Salmonella Enteritidis and 7 mg/mL for Pseudomonas aeruginosa. For Staphylococcus epidermidis the MIC was 0.11 mg/mL and the MBC was 0.22 mg/mL. Escherichia coli was inhibited with MIC of 0.88 mg/mL and MBC of 1.75 mg/mL. Equivalence between MIC and MBC was observed for methanolic extract against S. epidermidis (9.75 mg/mL). For S. aureus, the MIC of this extract was 9.75 mg/mL and the MBC 78 mg/mL. They were resistant to such extract: E. coli, S. Enteritidis and P. aeruginosa. Chloroform and ethyl acetate extracts were bacteriostatic against the five strains, but chloroform inhibited them all with MICs of 15 mg/mL, while ethyl acetate had MICs of 7.56 mg/mL for S. aureus, 1.89 mg/mL for S. epidermidis, 15.12 mg/mL for S. Enteritidis and 30.25 mg/mL for E. coli and P. aeruginosa. Regarding cytotoxicity, the essential oil compromised the cell viability of the Vero E6 line, only at the highest concentration, 4.4 mg/mL, inhibiting about 93.91% in 24h and 94.26% in 48h. In HeLa cells, in 24h the oil at the same dose had inhibition of 21%, which after 48h increased to 44.3%, showing a possible antitumor action. For the non-tumor cell line HEK-293, the oil had no toxic effect. It is concluded that the results are promising, opening future prospects for M. urundeuva leaf products being pharmacologically viable.