京都大学 / 0048 / 新制・課程博士 / 博士(薬学) / 甲第18207号 / 薬博第797号 / 新制||薬||237(附属図書館) / 31065 / 京都大学大学院薬学研究科創薬科学専攻 / (主査)教授 中山 和久, 教授 掛谷 秀昭, 准教授 伊藤 美千穂 / 学位規則第4条第1項該当 / Doctor of Pharmaceutical Sciences / Kyoto University / DFAM

Submitted by Franciele Moreira (francielemoreyra@gmail.com) on 2017-12-26T16:15:27Z No. of bitstreams: 2 Dissertação - Lucas Daniel Quinteiro de Oliveira 2017.pdf: 3361217 bytes, checksum: f1ea8dda888ba50d64581258f8ca97cd (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Rejected by Luciana Ferreira (lucgeral@gmail.com), reason: Olha a unidade acadêmica é IPTSP e não FM on 2017-12-27T10:44:54Z (GMT) / Submitted by Franciele Moreira (francielemoreyra@gmail.com) on 2017-12-27T12:11:57Z No. of bitstreams: 2 Dissertação - Lucas Daniel Quinteiro de Oliveira 2017.pdf: 3361217 bytes, checksum: f1ea8dda888ba50d64581258f8ca97cd (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Approved for entry into archive by Luciana Ferreira (lucgeral@gmail.com) on 2017-12-28T09:29:42Z (GMT) No. of bitstreams: 2 Dissertação - Lucas Daniel Quinteiro de Oliveira 2017.pdf: 3361217 bytes, checksum: f1ea8dda888ba50d64581258f8ca97cd (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) / Made available in DSpace on 2017-12-28T09:29:42Z (GMT). No. of bitstreams: 2 Dissertação - Lucas Daniel Quinteiro de Oliveira 2017.pdf: 3361217 bytes, checksum: f1ea8dda888ba50d64581258f8ca97cd (MD5) license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Previous issue date: 2017-10-26 / Fundação de Amparo à Pesquisa do Estado de Goiás - FAPEG / The Cryptococcus neoformans complex comprises two species responsible for causing cryptococcosis, the main manifestation being meningoencephalitis in immunocompromised hosts. Its pathogenicity is related to virulence factors. The treatment of this disease is difficult because the drugs present high toxicity, resistance of the fungus and little therapeutic efficiency. Research with biologically active natural products has shown that essential oils (OEs) have important antifungal activity. Thus, the present study had as objective to evaluate the antifungal efficacy and action on the virulence factors in C. neoformans complexes of OEs of Cinamomum cassia (Cinnamon of China) and Cybopogom flexuosus (Lemon Grass). By means of the microdilution technique in broth, OEs had MIC ranging from 8 to 256 μg / ml and CFM from 16 to 512 μg / ml. C. cassia promoted a 47.8% reduction in capsule size and inhibited melanin synthesis in 30% of the isolates. The evaluation of this OE on the activity of exoenzymes phospholipase, urease and DNAse demonstrated inhibition in 15%, 30% and 25% of the evaluated isolates respectively. C. flexuosus reduced the size of the capsule by 48.7%, inhibited the production of melanin, urease, phospholipase and DNAse by 30%, 30%, 25% and 15% respectively. The data demonstrated that the isolates did not produce proteinase and the hemolytic activity was reduced by 15% for C. cassia and 45% C. flexuous. The results highlight the potential of these OEs in the treatment of cryptococcosis as well as the inhibition of virulence factors. These data are promising, and further research is needed to develop of a new drug. / O complexo Cryptococcus neoformans compreende duas espécies, responsáveis por causar criptococose, sendo a principal manifestação a meningoencefalite em imunocomprometidos. Sua patogenicidade está relacionada aos fatores de virulência. O tratamento desta enfermidade é dificultado devido aos fármacos apresentarem alta toxicidade, resistência do fungo e pouca eficiência terapêutica. Pesquisa com produtos naturais biologicamente ativos tem demonstrado que os óleos essenciais (OEs) apresentam importante atividade antifúngica. Assim, o presente estudo teve como objetivo avaliar a eficácia como antifúngico e ação sobre os fatores de virulência em espécies do complexo C. neoformans dos OEs de Cinamomum cassia (Canela da China) e Cybopogom flexuosus (Capim limão). Por meio da técnica de microdiluição em caldo, os OEs apresentaram CIM variando entre 8 a 256 μg/ml e CFM de 16 a 512 μg/ml. C. cassia promoveu uma redução de 47,8% no tamanho da cápsula e inibiu a síntese de melanina em 30% dos isolados. A avaliação deste OE sobre da atividade das exoenzimas fosfolipase, urease e DNAse demonstrou inibição em 15%, 30% e 25% dos isolados avaliados respectivamente. C. flexuosus reduziu o tamanho da cápsula em 48,7%, inibiu a produção de melanina, urease, fosfolipase e DNAse em 30%, 30%, 25% e 15% respectivamente. Os dados demonstraram que os isolados não produziram proteinase e a atividade hemolítica foi reduzida em 15% para C. cassia e 45% C. flexuosos. Os resultados enaltecem o potencial desses OEs no tratamento da criptococose assim como na inibição dos fatores de virulência. Esses dados são promissores, sendo necessário pesquisas mais aprofundadas para o desenvolvimento de um novo fármaco.

M.Tech. / There are over 250 cinnamon species existing worldwide, and amongst them, 2 species Cinnamomum cassia and Cinnamomum zeylanicum, are commonly used all over the world as spices, fragrances in perfumes and as medicines. These two species are distinguished from each other by the presence and absence of certain compounds depending on the origin and distribution of the plant. Nevertheless, all cinnamon species contain essential oils and water soluble components and the composition of these components found in each species depends on the type of species involved. These components are made up of phenyl propanoids, terpenes, flavonoids and saponins. In general, the essential oil component contains the following compounds: cinnamaldehyde as a major constituent with its derivatives cinnamic acid, cinnamyl alcohol, ethyl cinnamate, cinnamyl acetate and 2-methoxy cinnamaldehyde; eugenol; linalool; coumarin; carvone; carvacrol and β-caryophyllene. Most of these compounds are abundantly found in the bark except in the case of eugenol which is found in either leaves or bark depending on the species involved. The other water soluble component is composed of a group of compounds such as tannin, chalcone, catechins and anthocyanidins. These compounds polymerize to form methyl hydroxy chalcone polymers (MHCP) which has been shown to play an important role in lowering blood sugar levels in Type ll diabetic individuals. It is said that MHCP has an ability to promote the phosphorylation process which in turn activates the beta-cells and thereby creating insulin activity that will then convert glucose into glycogen. Besides all health benefits of cinnamon, the plant contains a toxic compound, coumarin which impacts badly on animals resulting in death, and little information on its toxicity to human beings has been documented. Concerns arose about the possible presence of coumarin in these formulations, since these formulations are made from the cinnamon and the plant contains coumarin. This work has investigated the potential toxicity of coumarin from cinnamon powder and cinnamon formulation. The components from both cinnamon samples were extracted using various solvents according to their polarities and these compounds were screened on thin layer chromatography (TLC). The essential oil components were separated by column chromatography, and quantified by using high performance liquid chromatography (HPLC), all components (essential oil and water soluble) were identified by HPLC, and finally the characterization of the essential oil components was done with infrared (IR) and nuclear magnetic resonance (NMR) whereas those of the water soluble were characterized by using liquid chromatography coupled to a mass spectrometer (LC-MS).

Submitted by Edisangela Bastos (edisangela@ufpa.br) on 2018-09-14T17:56:45Z No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Tese_EssentialOilsComponents.pdf: 4263439 bytes, checksum: c1189e55f12d63ca94f4a519200746ce (MD5) / Approved for entry into archive by Edisangela Bastos (edisangela@ufpa.br) on 2018-09-14T17:57:50Z (GMT) No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Tese_EssentialOilsComponents.pdf: 4263439 bytes, checksum: c1189e55f12d63ca94f4a519200746ce (MD5) / Made available in DSpace on 2018-09-14T17:57:50Z (GMT). No. of bitstreams: 2 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) Tese_EssentialOilsComponents.pdf: 4263439 bytes, checksum: c1189e55f12d63ca94f4a519200746ce (MD5) Previous issue date: 2017-03-31 / Óleos essenciais derivados do metabolismo secundário de plantas podem ter atividades contra nematóides das galhas, Melodogyne incognita. Devido à necessidade de nematicidas mais eficientes e menos tóxicos para o homem e para o ambiente do que os disponíveis para o controle de Meloidogyne incognita, assim, neste trabalho objetivou-se estudar os óleos essenciais de Cinnamomum cassia e de Allium sativum, que foram descritos como ativos in vitro contra o nematóide Bursaphelenchus xylophilus. O óleo essencial de ambas as espécies foi obtido por hidrodestilação, dissolvidos em solução aquosa de Tween 80 a 0,01 g mL-1 e testado in vitro contra M. incognita. A 62 μg mL-1 as emulsões dos óleos foram mais ativas sobre ovos e juvenis de segundo estagio (J2) do que o Carbofuran a 173 μg mL-1. De acordo com a análise de cromatografia gasosa-espectrometria de massas, o constituinte majoritário de C. cassia é o (E)-cinamaldeído (83,3%), enquanto para o óleo de alho foram trisulfeto de dialila (66.7%) e dissulfeto de dialila (21.3%). Esses constituintes explicaram a atividade nematicida in vitro do óleo essencial de cada espécie de planta. A emulsão do óleo de C. cassia (500 μg mL-1), (E)-cinamaldeído (416 μg mL-1) e alho (250 μg mL-1) reduziram o numero de galhas e de ovos em plantas de soja e tomateiro, respectivamente, a valores estatisticamente iguais àquele obtido pelo Carbofuran (416 μg mL-1). Vapores dos óleos essenciais e do (E)-cinamaldeído foram ativos tanto quanto o nematicida fumigante Basamid usado nos ensaios in vitro contra M. incognita. A infectividade e a reprodução de M. incognita em plantas de soja e de tomate cultivadas em substrato infestado artificialmente com ovos do nematóide e tratado com 0,2 mL (alho), 1,0 mL (E)-cinamaldeído e 0,25 g de Basamid foram estatisiticamente iguais entre si na redução da população do nematoide. Esses resultados inequivocamente provam a atividade nematicida dos óleos essenciais e da substância (E)-cinamaldeído contra M. incognita, portanto, tanto o óleo quanto o (E)-cinamaldeído são muito promissores ao desenvolvimento de novos nematicidas fumigantes para o controle de nematóides em plantas de soja e de tomate. / Essential oils derived from secondary plant metabolism may have activities against root-knot nematodes, Meloidogyne incognita. Because nematicides that are more efficient and less toxic to humans and the environment than those available are desirable to control this pathogen, this work aimed at studying the essential oil of Cinnamomum cassia and Allium sativum, which were described as active in vitro against the nematode Bursaphelenchus xylophilus. The essential oils of both species were obtained by hydrodistillation, initially dissolved in aqueous solution of Tween 80 at 0.01 g mL-1 and tested in vitro against M. incognita. At 62 μg mL-1 the oil emulsions were more active on eggs and second stage juveniles (J2) than Carbofuran at 173 μg mL-1. According to gas chromatography-mass spectrometry analysis, the major constituent of C. cassia is (E) -cinnamaldehyde (83.3%), while for garlic oil were diallyl trisulfide (66.7%) and diallyl disulfide (21.3%). These constituents explained the in vitro nematicidal activity of the essential oil of each plant species. The emulsion of the C. cassia (500 μg mL-1), E)-cinnamaldehyde (416 μg mL-1) and garlic (250 μg mL -1) reduced the number of galls and eggs in roots soybean and tomatoes to values statistically equal to those obtained with Carbofuran at 415 μg mL-1. Vapors from the essential oils and (E)-cinnamaldehyde were active as much as the basamid fumigant nematicide used in the in vitro assays against M. incognita. Infectivity and reproduction of M. incognita in soybean and tomato plants grown on substrate artificially infested with nematode eggs and treated with 0.2 mL (garlic), 1.0 mL (E)-cinnamaldehyde and 0.25 g of Basamid were statistically equal among themselves in reducing the nematode population. These results unequivocally proofs of the nematicidal activity of the essential oils and of the (E)-cinnamaldehyde substance against M. incognita, therefore, both oil (E)-cinnamaldehyde are very promising to the development of new fumigant nematicides for the control of nematodes in soybean and tomato plants. / UFPA/Altamira