Thesis (MSc)--Stellenbosch University, 2012 / ENGLISH ABSTRACT: The aroma and flavour of wine are important aspects that form the basis for consumers’ organoleptic experience of wine. Therefore, an understanding of the chemical composition of wine aroma is of major importance, to establish possible links between wine chemistry, sensory attributes and consumer preference for a product. For this purpose analytical chemistry and multivariate techniques are indispensable tools for the metabolic profiling of wine. Chenin blanc is one of the most important South African export white wine varieties. However, despite its importance, very limited profiling of Chenin blanc aroma compounds has been done and information is restricted to isolated and dated reports on a few chemical compounds only. Therefore, the overall aim of this study was to obtain an in-depth view of the volatile chemical profile of this cultivar. The first task was to perform targeted volatile metabolic profiling of the three dry and offdry Chenin blanc styles, fresh and fruity, rich and ripe unwooded and rich and ripe wooded. To this end, a new, simple and robust liquid-liquid extraction technique using dichloromethane was developed and validated for extraction of analytes prior to gas chromatography flame ionization detection (GC-FID) analysis, to quantify 57 analytes in one rapid analytical procedure. This method was applied to profile 48 Chenin blanc wines. Very successful discrimination between the three styles, using the quantified volatile compounds, was obtained with two multivariate methods. These were partial least squares regression-discriminant analysis, (PLS-DA), as well linear-DA, using best subset selection for identifying the most important variables. According to the classification models, a higher content of maturation derived, malolactic fermentation derived and wood derived compounds were predominantly characteristic of the wooded wines. Higher content of some terpenes and ethyl esters were predominantly associated with the rich and ripe unwooded style Chenin blanc wines, while the fresh and fruity style were generally characterized by high levels of acetate esters. Secondly, untargeted analysis of 21 wines was done with gas chromatography mass spectrometry (GC-MS). Mathematical chromatography, using PARAllel FACtor analysis (PARAFAC and PARAFAC2), was applied to the GC-MS data for resolution of the complex chromatographic results by multi-way modeling, and to derive unbiased multivariate classification models of the three styles. This approach provided excellent style differentiation, without the arduous task of analysis of numerous standards and setting up of calibration curves, required by the targeted approach described above. Additionally, the data generated during this study will form part of the current South African wine aroma database, which does not contain any data regarding Chenin blanc at present. / AFRIKAANSE OPSOMMING: Die aroma en geur van wyn is belangrike aspekte aangesien dit die basis vorm van die wynverbruiker se organoleptiese ervaring van die produk. Derhalwe, is ‘n deeglike kennis van die chemiese samestelling van wynaroma baie belangrik, ten einde die korrelasies tussen wynchemie, sensoriese eienskappe en verbruikersvoorkeure te bepaal. Vir hierdie doel, is die insameling van analitiese chemiese data, tesame met multi-veranderlike tegnieke om relevante inligting uit die data te onttrek, onmisbaar vir die metaboliese profilering van wyn. Chenin blanc is huidiglik een van Suid-Afrika se belangrikste uitvoer wit wynvariëteite. Ten spyte hiervan, is daar tot hede egter baie min profilering van Chenin blanc se aromakomponente gedoen en die beskikbare inligting is beperk tot geïsoleerde en verouderde navorsingsbevindinge. In die lig van bogenoemde, is die oorkoepelende motivering vir hierdie studie dus om die vlugtige chemiese komponente se profiel in Chenin blanc wyn, in diepte te bepaal. Die eerste taak was die geteikende bepaling van die metaboliese profiel van drie droë of halfdroë Chenin blanc wynstyle, nl. vars en vrugtig, ryk en ryp ongehout, asook ryk en ryp gehout. Om dit te bereik, is ‘n nuwe eenvoudige en robuuste vloeistof-vloeistof ekstraksieprosedure met dichlorometaan ontwikkel, wat analise met gaschromatografie – vlamionisasie deteksie (GC-FID) voorafgaan, om die konsentrasies van 57 komponente in een vinnige analise te bepaal. Hierdie metode is gebruik om 48 Chenin blanc wyne te profileer. Deur gebruik te maak van multi-veranderlike data analitiese tegnieke, is die gekwantifiseerde vlugtige komponente data gebruik in diskriminant analise. Baie suksesvolle onderskeid tussen die drie style, is verkry deur gebruik te maak van twee multi-veranderlike metodes, naamlik: parsiële kleinste kwadrate regressie, diskriminant analise, asook liniêre diskriminant analise. Vir laasgenoemde analise, is die seleksie van die mees belangrike veranderlikes met beste sub-groep regressie bepaal. Volgens hierdie klassifikasie modelle is ‘n hoër inhoud van veroudering-, appelmelksuurgisting- en houtverwante aroma komponente baie kenmerkend in die houtbehandelde wyne. Hoër vlakke van sommige terpene en etiel esters was kenmerkend met betrekking tot ryk en ryp ongehoute Chenin blanc style, terwyl die vars en vrugtige style meer gekenmerk was met hoë vlakke van asetaat esters. Tweedens is ‘n seleksie van 21 wyne geanaliseer deur gebruik te maak van gaschromatografie – massa spektrometrie (GC-MS) in ‘n ongeteikende metaboliese profileringsbenadering. Wiskundige chromatografiese metodes, spesifiek, parallelle faktor analise (PARAllel FACtor analysis (PARAFAC and PARAFAC2)), was voorts gebruik om komplekse chromatogramme te prosesseer met wiskundige, multi-vlak modellering. Met hierdie nie-selektiewe benadering, is ook suksesvolle klassifikasiemodelle gegenereer vir die diskriminasie tussen die drie verskillende Chenin blanc style. Die voordeel van die ongeteikende GC-MS analise, gekoppel met die data hanterings- en prosesseringsprotokols in hierdie studie gebruik, is dat die arbeidsintensiewe taak om kalibrasiekurwes op te stel vir elke individuele komponent, soos wat vereis word in die geteikende benadering, nie nodig is nie. Die data wat ingewin is gedurende hierdie studie, sal ook bygevoeg word tot ‘n bestaande Suid-Afrikaanse aroma databasis, wat tans geen data aangaande Chenin blanc wyn bevat nie.

L'imagerie hyperspectrale de proximité est un outil prometteur pour le phénotypage ou la surveillance de la végétation. En association avec la régression des moindres carrés partiels ou PLS-R, elle permet de construire des cartographies de haute résolution spatiale du contenu chimique à l’échelle de la canopée. Cependant, plusieurs phénomènes optiques doivent être pris en compte lors de l'application de cette approche aux scènes de végétation dans des conditions naturelles. Notamment, les facteurs additifs et multiplicatifs liés respectivement à la réflexion spéculaire et à l'inclinaison des feuilles qui peuvent être surmontés par prétraitement. Mais le phénomène qui pose le plus de défis est la réflexion multiple. Il se produit lorsqu'une feuille est éclairée en partie par la lumière directe, et en partie par la réflexion ou la transmission de la lumière des feuilles voisines, induisant de forts effets non linéaires sur son spectre de réflectance. Bien que cet effet puisse être pris en compte dans certains modèles de télédétection à l’échelle de la canopée, aucune étude n’a été proposée à ce jour sur la façon dont un tel phénomène affecte les évaluations spectrales de la biochimie végétale par imagerie de proximité. L'objectif de la présente étude était d'analyser ces effets dans le contexte de l'imagerie hyperspectrale à des fins de phénotypage végétal et de proposer des méthodes chimiométriques pour les surmonter. Le développement méthodologique a été basé sur des outils de simulation inclus dans la plate-forme open source OpenAlea (http://openalea.gforge.inria.fr/dokuwiki/doku.php). Une scène typique de canopée de blé a été modélisée à l'aide du modèle Adel-Wheat et combinée au modèle de propagation de la lumière Caribu. L'outil proposé simule la réflectance apparente de chaque feuille visible dans la canopée pour une réflectance et une transmittance réelles données, permettant de synthétiser des images hyperspectrales réalistes. Cette approche par simulation nous a permis, dans un premier temps, d’analyser la distribution dans l’espace spectral des perturbations engendrées par les réflexions multiples, puis d’en déduire une méthode de correction applicable dans le cas d’une régression PLS. La méthode est basée sur la construction de deux sous-espaces W et B générés respectivement par la formulation analytique des réflexions multiples et la variable d'intérêt. Ceci nous permet alors de définir une matrice de projection sur B selon la direction W (projection oblique), qui permet de supprimer l’effet des réflexions multiples tout en conservant l’information utile. Il suffit ensuite d’appliquer cette projection à chaque spectre lors de l’apprentissage et de la mise en œuvre du modèle PLS. La méthode a d’abord été développée et paramétrée sur les données simulées, dans le contexte de l’évaluation de la teneur en azote (LNC) de feuilles de blé. Pour cela, les spectres de réflectance (450-1100 nm) de 57 feuilles de blé ont été collectés à l'aide d'un spectromètre ASD (FieldSpec®, Analytical Spectral Devices, Inc., Boulder, Colorado, USA), tandis que leur LNC a été mesuré à l'aide d'analyses chimiques. Des modèles de régression avec et sans projection oblique ont alors été construits à partir des spectres ASD et appliqués sur l’ensemble des données simulées. Le modèle avec projection oblique a donné d’excellents résultats (R² = 0.931; RMSEP = 0.29% DM) en comparaison du modèle classique (R² = 0.915; RMSEP = 0.42% DM).La même méthode a ensuite été appliquée en conditions réelles, sur des feuilles de blé cultivées en pot et au champ. Pour cela, des feuilles ont été collectées et imagées à plat sur fond noir pour la construction des modèles PLS, qui ont ensuite été appliqués aux plantes sur pied. Ces expérimentations ont confirmé d’une part que la PLS-R classique entraînait une forte surestimation du LNC sur les feuilles entourées d’autres feuilles, d’autre part que la projection oblique évitait cette surestimation. / Short range hyperspectral imagery is a promising tool for phenotyping and vegetation survey. When associated with partial least square regression (PLS-R), it allows high spatial resolution mapping of the plant chemical content at the canopy scale. However, several optical phenomena have to be taken into account when applying this approach to vegetation scenes in natural conditions. For instance, additive and multiplicative factors due respectively to specular reflection and leaf inclination can be overcome by spectral preprocessing. But the most challenging phenomenon is multiple scattering. It appears when a leaf is partly lightened by the reflected or transmitted light from surrounding leaves, resulting in strong non linear effects in its apparent reflectance spectrum. Though this effect can be taken into account in some remote sensing models at the canopy scale, no study has been proposed until now concerning its impact on spectral prediction of vegetation chemical content by short range imagery.The objective of this project, associated with a PhD work, was to analyze these effects in the context of hyperspectral imagery for vegetation phenotyping purpose, and to propose spectral processing methods to overcome them.The methodological development has been based on simulation tools included in the open source platform OpenAlea (http://openalea.gforge.inria.fr/dokuwiki/doku.php). A typical wheat canopy scene has been modelled using Adel-Wheat and combined with the light propagation model Caribu. The proposed tool simulates the apparent reflectance of every visible leaf in the canopy for a given actual reflectance and transmittance, allowing to synthetize realistic hyperspectral images.This simulation approach has allowed us, in a first step, to analyze the distribution of deviations due to multiple scattering in the spectral space, and then to infer a correction method in the frame of PLS regression. This method relies on the building of two subspaces EW and EB respectively generated by the analytic formulation of multiple scattering and by the variable of interest. It allows us to define a projection operation on EB subspace along EW direction (oblique projection), in order to remove multiple scattering effects while preserving useful information. This projection operation is then applied on every spectra during learning phase and using phase of the PLS model.The method has first been developed and tuned using simulated data, in the frame of leaf nitrogen content (LNC) prediction of wheat leaves. For this purpose, reflectance spectra (450-1100 nm) of 57 wheat leaves have been collected using a ASD filed spectrometer (FieldSpec®, Analytical Spectral Devices, Inc., Boulder, Colorado, USA), while their LNC was measured through reference chemical analyses. Regression models with and without oblique projection have then been built from the ASD spectra and applied to simulated data. The model with oblique projection provided excellent results (R² = 0.931; RMSEP = 0.29% DM), compared to the classical one (R² = 0.915; RMSEP = 0.42% DM).The same method has then been applied in real conditions on wheat pot plants and field plants. For this purpose, some leaves have been collected and laid on a black paper background to be imaged, in order to build PLS models that have then been applied on in-situ plants. These experimentations have confirmed that the classical PLS-R induces a strong overestimation of LNC on leaves surrounded by other leaves, and that oblique projection corrects this overestimation (same prediction on surrounded then isolated leaf).

Made available in DSpace on 2015-05-14T13:21:15Z (GMT). No. of bitstreams: 1 Arquivototal.pdf: 1879228 bytes, checksum: 90c7da6ef56a230fab2ca924b5d230db (MD5) Previous issue date: 2012-08-20 / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES / The clay mineral vermiculite was modified by intercalation of ethylenediamine (en) in acidic medium based on a 24 factorial design, the selected variables were: temperature of the intercalation reaction, concentration of en+, time under stirring and acid leaching of the vermiculite. Sixteen different experimental conditions were carried out and the evaluated response was the percentage of nitrogen in each sample. The pristine and modified matrices were characterized through the following techniques, elemental analysis of CHN, x-ray diffraction, infrared spectroscopy, nuclear magnetic resonance for 29Si nucleus. A chemometric study was performed by using the sixteen infrared spectra to investigate the effect of the experimental conditions in the modification of vermiculite. The results showed that temperature of the reaction and the leaching process of the solid have relevant influence in terms of structural properties of vermiculite. The elemental analysis data gave 0.54 mmol g-1 for the amount of organic groups, suggesting the effectiveness of the intercalation reaction of protonated ethylenediamine (en+) in the interlayer space of the material. The solid obtained under optimized conditions was applied to adsorption of the reactive dye Remazol Blue RN from aqueous solutions, by using a 22 factorial design, the variables studied were: temperature and time of reaction, and the response was given by the UV-Vis absorption of the dye typical band. The results showed that the modified vermiculite is an efficient adsorbent for removing of Remazol blue RN from aqueous solution and the application of experimental design is important for determining the best conditions for the experimental variables. / O argilomineral vermiculita foi modificado por intercalação de etilenodiamina (en) em meio ácido. Para isto, foi empregado um planejamento fatorial 24, cujos fatores escolhidos foram: temperatura da reação de intercalação, concentração de en+, tempo de agitação e lixiviação da vermiculita, no total foram obtidas 16 amostras de vermiculita preparadas em diversas condições experimentais. A resposta avaliada foi a percentagem de nitrogênio. As matrizes pura e modificadas foram caracterizadas através das técnicas de análise elementar de CHN; difração de raios X; espectroscopia na região do infravermelho e ressonância magnética nuclear de 29Si. Um estudo quimiométrico foi realizado utilizando os espectros na região do infravermelho das 16 amostras para investigar o efeito das condições experimentais na modificação de vermiculita. Os resultados mostraram que a temperatura de reação e o processo de lixiviação do sólido tem influência relevante em termos de propriedades estruturais da vermiculita. Os dados de análise elementar forneceram o valor de 0,54 mmol g-1 para a quantidade de grupos orgânicos, sugerindo a efetividade da reação de intercalação de etilenodiamina protonada (en+) no espaço interlamelar do material. O sólido otimizado foi aplicado em processo de adsorção do corante reativo azul de remazol RN em solução aquosa, utilizando o planejamento fatorial, na qual as variáveis foram: temperatura e tempo de agitação, as respostas foram dadas pela absorção no UV-VIS da banda característica do corante. Os resultados mostraram que a vermiculita modificada é um adsorvente eficiente para a remoção do corante reativo azul de remazol RN em solução aquosa e que a aplicação do planejamento experimental é importante para a determinação das melhores condições das variáveis experimentais.

Submitted by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2018-10-18T14:39:20Z No. of bitstreams: 3 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) TeseParcial(Cap.I)-RaimundoJunior-PPGQ.pdf: 1178770 bytes, checksum: 74333ca704cd865ec51c2e655679a37f (MD5) Reprodução Não Autorizada.pdf: 47716 bytes, checksum: 0353d988c60b584cfc9978721c498a11 (MD5) / Approved for entry into archive by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2018-10-18T14:39:33Z (GMT) No. of bitstreams: 3 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) TeseParcial(Cap.I)-RaimundoJunior-PPGQ.pdf: 1178770 bytes, checksum: 74333ca704cd865ec51c2e655679a37f (MD5) Reprodução Não Autorizada.pdf: 47716 bytes, checksum: 0353d988c60b584cfc9978721c498a11 (MD5) / Made available in DSpace on 2018-10-18T14:39:33Z (GMT). No. of bitstreams: 3 license_rdf: 0 bytes, checksum: d41d8cd98f00b204e9800998ecf8427e (MD5) TeseParcial(Cap.I)-RaimundoJunior-PPGQ.pdf: 1178770 bytes, checksum: 74333ca704cd865ec51c2e655679a37f (MD5) Reprodução Não Autorizada.pdf: 47716 bytes, checksum: 0353d988c60b584cfc9978721c498a11 (MD5) Previous issue date: 2018-05-28 / The Myrtaceae family has 132 genera distributed in 5,760 species present in Australia, Southeast Asia, tropical and temperate America. In Brazil, it presents 1,018 species in 23 genera. Myrcia D.C is one of the largest genera with 282 species present in almost all territory, of which 220 are endemics. Its species are used in Brazilian popular medicine, with emphasis on Myrcia spp., which are used by the traditional population of the Amazon as astringents, diuretics, hypoglycemics, antihemorrhagics, antioxidants and in the treatment of hypertension and ulcers. The present study has evaluated the chemical composition of the essential oils of 13 species of Myrtaceae (Myrcia spp., Marlierea sp. and Calyptranthes sp.) from the Terra Firme ecosystem (Amazon). In addition, the cytotoxic, antibacterial, bacteriostatic, antifungal and larvicidal potentials of these oils have been described. Twenty-seven samples belonging to these thirteen species (18 individuals of 11 species of Myrcia, one of Marlierea caudata and one of Calyptranthes spruceana) were collected from the Adolpho Ducke Forest Reserve, EMBRAPA (Manaus) and the PANC site (Manaus). Its essential oils were obtained by hydrodistillation, dried and stored under refrigeration. The chemical characterization was carried out by means of CG-DIC and CG-EM analysis. The Arithmetic Indexes and the Spectral Similarity Indexes were obtained, whose results were compared with those described in the main databases. The mean chemical characterization of these oils was 95%, totaling 336 compounds identified, of which 34 have been abundant (50.7 to 96.17%). The most frequent and, in some cases, the most frequent components are: (E)-caryophyllene, δ-cadinene, Espatulenol, α-Copaene, β-elemene, α-humulene, Caryophyllene oxide, β-selinene, α-muurolene and α–cadinol (42.73% of nonoxygenated sesquiterpenes and 36.98% of oxygenated sesquiterpenes). This chemical variability is common to Myrcia species of other Brazilian ecosystems/biomes. Of the seven pairs of Myrcia individuals collected in distinct periods (dry and rainy), 242 compounds were identified, of which 125 were common, 41 and 76 of which were unique to the rainy and dry periods, respectively. Essential oils of the dry period have exhibit greater chemical variability. In addition, the chemical variability of the essential oils of Myrcia spp. of this ecosystem has been described by 51 cyclization pathways. Of these routes, thirteen have a high frequency (above 50%), four of which are the most prominent ones (Cariofilan, Cadinano, Aromadendrano and Eudesmano). The chemical results of this study have revealed a clear agreement of the chemical composition of Marlierea caudata with the chemistry composition of Myrcia spp.. On the other hand, this observation is not clearly evident for C. spruceana. Moreover, It should be noted that the chemical composition of the essential oils of M. magnoliifolia, M. minutiflora, M. fenestrata, M. amapensis and Marlierea caudata have been described for the first time. As for toxicity to cancer cells (Skmel 3 and ACPO2) and normal cells (MRC5), M. minutiflora presents moderate activity for human melanoma (Skmel 3) and gastric adenocarcinoma (ACPO2) as well as cytotoxic to non-neoplastic fibroblasts (MRC5). M. citrifolia, M. minutiflora, M. paivae and M. magnoliifolia present moderate to high activity against Staphylococcus aureus. M. fallax, M. sylvatica, M. paivae and C. spruceana present moderate activity against Staphylococcus aureus. As for the bacteriostatic action, all species tested have shown moderate to high activity against Pseudomonas aeroginosas. In relation to the insecticidal activity, M. citrifolia, M. bracteata, M. fenestrata, M. amazonica, M. paivae and C. spruceana are active, since after 24 h the mortality percentage of Aedes aegypti larvae was 100% in 25 mg.L- 1 of essential oil. Furthermore, the use of chemometric tools in this study has shown it possible to observe the segregation of samples by major terpene groups and their most influential cyclic pathways, whose substances of major relevance in this model have been (E)-Caryophyllene, δ-Cadinene, and Espatulenol. Its pharmacological activities described in the literature should suggest that they are responsible for the biological results observed in this work. However, novel biological assays with such isolated constituents must be necessary. Therefore, with respect to the chemistry of Myrcia volatile constituents occurring in Terra Firme (Amazonia), the present study has been evidenced very characteristic Amazonian chemotypes and without similarity with other species collected outside the region, which leads us to conclude how much to must be studied from the precious Amazonian biodiversity. / A família Myrtaceae apresenta 132 gêneros distribuídas em 5.760 espécies presentes na Austrália, sudeste da Ásia, América tropical e temperada. No Brasil, apresenta-se com 1018 espécies em 23 gêneros. Myrcia D.C é um dos maiores gêneros com 282 espécies presentes em quase todo território, sendo 220 endêmicas. Suas espécies são empregada na medicina popular brasileira, com destaque para Myrcia spp., as quais são usadas pela população tradicional da Amazônia como adstringentes, diuréticos, hipoglicemicas, anti-hemorrágicas, antioxidantes e no tratamento de hipertensão e úlceras. O presente estudo avalia a composição química dos óleos essenciais de 13 espécies de Myrtaceae (Myrcia spp., Marlierea sp. e Myrciaria sp.) de ecossistema de Terra Firme (Amazônia). Além disso são descritos os potenciais citotóxico, antibacteriano, bacteriostático, antifúngico e larvicida desses óleos. Vinte sete amostras pertencentes a essas treze espécies (18 indivíduos de 11 espécies de Mycia, um indivíduo de Marlierea caudata e outro de Calyptranthes spruceana) foram coletados na Reserva Florestal Adolpho Ducke, na EMBRAPA (Manaus) e no sítio PANC (Manaus). Seus óleos essências foram obtidos por hidrodestilação, secos e armazenado sob refrigeração. A caracterização química ocorreu por meio de análises por CG-DIC e CG-EM, cujos Índices Aritiméticos calculados e de Similaridade Espectral foram comparados com os descritos nas principais bases de dados. A média de caracterização química desses óleos foi de 95%, totalizando 336 substâncias identificadas, das quais 34 são abundantes (50,7 a 96,17%). Os componentes mais frequentes, e em alguns casos majoritários, são: (E)–cariofileno, δ–cadineno, Espatulenol, α–copaeno, β–elemeno, α–humuleno, Óxido de cariofileno, β–selineno, α–muuroleno e α–cadinol, prevalecendo estruturas sesquiterpênicas (42,73% de sesquiterpenos não-oxigenados e 36,98% de sesquiterpenos oxigenados). Essa variabilidade química é comum a espécies de Myrcia de outros ecossistemas/biomas brasileiros. Dos sete pares de indivíduos de Myrcia coletados em períodos distintos (seco e chuvoso), identificou-se 242 substâncias, sendo 125 comuns, com 41 exclusivas do período chuvoso e 76 são exclusivos do períoso seco. Os óleos essenciais do período seco apresentaram uma maior variabilidade química. Além disso, a variabilidade química dos óleos essenciais de Myrcia spp. desse ecossistema pôde ser descrita por 51 vias de ciclização. Dessas vias, treze apresentam elevada frequência (superior a 50%), sendo quatro vias de destaque pela maior ocorrência (Cariofilano, Cadinano, Aromadendrano e Eudesmano). Os resultados químicos desse estudo revelam uma clara concordância de Marlierea caudata com a química de Myrcia spp., porém o mesmo não se evidencia claramente para C. spruceana. Ressalta-se que a composição química dos óleos essenias de M. magnoliifolia, M. minutiflora, M. fenestrata, M. amapensis e Marlierea caudata são descritos pela primeira vez. Quanto à toxicidade frente a células cancerígenas (Skmel 3 e ACPO2) e normais (MRC5), M. minutiflora apresenta atividade moderada para melanoma humano (Skmel 3) e adenocarcinoma gástrico (ACPO2), bem como citotóxica para fibroblastos nãoneoplásicos (MRC5). M. amazonica e M. fenestrata também apresentam atividade moderada para Skmel 3. Quanto ao potencial antimicrobiano e bacteriostático, M. citrifolia, M. minutiflora, M. paivae e M. magnoliifolia apresentam atividade moderada a elevada frente a Staphylococcus aureus. M. fallax, M. sylvatica, M. paivae e C. spruceana apresentam atividade moderada frente a Staphylococcus aureus. Quanto a ação bacteriostática, todas as espécies ensaiadas apresentam atividade moderada a elevada frente a Pseudomonas aeroginosas. Em relação a atividade inseticida, M. citrifolia, M. bracteata, M. fenestrata, M. amazonica, M. paivae e C. spruceana são ativas, pois após 24 h o percentual de mortalidade das larvas de Aedes aegypti é de 100% em 25 mg.L-1 de óleo essencial. A aplicação de ferramentas quimiométricas nesse estudo possibilitou observar a segregação das amostras por grupos terpênicos majoritários e suas vias de ciclização mais influentes, cujas substâncias de maior relevância nesse modelo são: (E)-cariofileno, δ–cadineno e Espatulenol. Suas atividades farmacológicas descritas na literatura sugerem serem os responsáveis pelos resultados biológicos observados nesse trabalho. Contudo, novos ensaios biológicos com tais constituintes isolados talvez sejam necessários. Portanto, a respeito da química dos constituintes voláteis de Myrcia ocorrentes em Terra Firme (Amazônia), o presente estudo evidência quimiotipos amazônicos bem característicos e sem similaridade com outras espécies coletadas fora da região, o que nos leva a concluir o quanto ainda há a ser estudado a partir da preciosa biodiversidade amazônica.

In the recent years, the consumer choices have been focused on health-promoting plant-based food and their preferences are oriented towards regional foodstuff from local productions. Therefore, an important factor for vegetables grown Trentino-Alto Adige (Italy) is to point out the added value of alpine farming to evaluate the nutritional values of farming products. Omics technologies (e.g. genomics, transcriptomics, proteomics and metabolomics) are aimed at investigating the assessment of different pools of molecules and how they are translated into the structure, function, and dynamics of a biological system or systems in order to provide a comprehensive characterization of a specific organism. Research use the omics techniques to exhaustively understand the functionality of food components. Several sophisticated chromatographic methods, spectroscopic techniques and chemometric tools are applied to give an insight into a comprehensive overview of the intrinsic quality, typicality and regionality of specific plant-based foods in the present PhD thesis: apples and potatoes. The quality of these foods is evaluated by quantifying the secondary metabolites to investigate their nutraceutical values. The aim of this PhD project is to use several analytical techniques (LC-MS, UV-VIS) that are capable of comprehensively characterizing the food metabolome with particular emphasis on those components with high nutritional values. The data analysis and data handling of omics data requires advanced bioinformatic, statistical, and chemometric tools. Potatoes and apples are chosen as target matrices for these studies for their relevance in the local economy and for the peculiar chemical composition of particular interest for their health-promoting proprieties. The information is acquired using several sophisticated chromatographic and spectroscopic techniques, such as ultra-high performance liquid chromatography coupled with triple quadrupole mass spectrometry (UHPLC– MS/MS) and UV/VIS. It is integrated to chemometric approaches (principal component analysis (PCA), partial least square regression (PLS), and data fusion) to achieve a comprehensive targeted chemical characterization. The sampling procedures gathers, in the case of the potatoes study, reference cultivars that may be found in the common retailers of Trentino/Alto-Adige and different production areas, the apples of 22 cultivars were harvest from the fields of the Laimburg Research Centre (Vadena, Italy) to guaranty comparability of the obtained data. Our results may be used as solid foundation for a reliable evaluation of apples and potatoes healthy "potential" value based on cutting-edge techniques, which are capable of providing comprehensive data regarding the alpine food quality parameters with high efficiency and reliability

京都大学 / 新制・課程博士 / 博士(農学) / 甲第24245号 / 農博第2524号 / 新制||農||1094(附属図書館) / 学位論文||R4||N5416(農学部図書室) / 京都大学大学院農学研究科地域環境科学専攻 / (主査)教授 近藤 直, 教授 飯田 訓久, 准教授 小川 雄一 / 学位規則第4条第1項該当 / Doctor of Agricultural Science / Kyoto University / DFAM

Thesis (MScEng (Process Engineering))--University of Stellenbosch, 2010. / Thesis submitted in partial fulfilment of the requirements for the degree of MASTER OF SCIENCE IN ENGINEERING (MINERAL PROCESSING) in the Department of Processing Engineering at the University of Stellenbosch / ENGLISH ABSTRACT: This work evaluates the use of inverse least squares (ILS) and classical least squares (CLS) models for calibration of a diffuse reflectance spectrophotometer for on-line monitoring of the aqueous phase in a flotation cells. Both models use a Beer's law for the quantification of the metals. The formulated statistical models are compared to a proprietary Blue Cube model in terms of prediction ability to determine the potential applicability of the models. A diffuse reflectance spectrophotometry was used for simultaneous analysis of copper (Cu), cobalt (Co) and zinc (Zn) in the solutions. The laboratory set-up of Blue Cube instrument was used for the experimental analysis. The concentrations and matrix compositions of the samples are simulated according to Skorpion zinc mine plant conditions. The calibration samples were prepared using a simplex-centroid mixture design with the triplicates of the centroid run. The unknown or test samples were prepared randomly within the same concentration of the calibration samples. The effects of temperature and nickel concentration on absorption of the metals were evaluated in the following range, 20 - 80 °C and 125 - 400 ppm, respectively. The statistical models (ILS and CLS) were calibrated from visible and near infrared (VNIR) spectra data of the calibration samples. A modified Beer's method was used as a preprocessing technique to convert the raw data into absorbance values. The manual wavelength selection procedure was used to select the wavelengths to be used in both models. The quality of the models was evaluated based on Rª and % root mean squared error (RMSE) values with 0.90 and 10% used as the guideline for the respective statistical parameters. Both ILS and CLS models showed good results for all three metals (Cu, Co and Zn) during their calibration steps. It was further shown that both models give worse predictions for Zn as compared to other metals due to its low relative intensity in the mixture. The derivative orders of absorbance spectra that were used to enhance the prediction results of Zn had no positive effect but they rather lowered accuracy of predictions. An increase in temperature was found to increase the intensities of the absorption spectra of all the metals while an increase in nickel concentration decreases the prediction ability of model. The developed statistical models were compared to a Blue Cube model in terms of prediction ability using analysis of variance (ANOVA) test. The ANOVA results revealed that there is no statistical difference between the developed models and Blue Cube model since the F-values for all the metals were below the critical F-value. Furthermore, the partial least squares (PLS) model shows an increased accuracy results for prediction of zinc metal as compared to both the ILS and CLS models. Finally, good comparisons of the statistical models results with atomic absorption spectroscopy (AAS) analyses were establish for the unknown samples. The study demonstrates that chemometric models (ILS and CLS) developed here can be used for quantification of several metals in real hydrometallurgical solutions as samples were simulated according to a plant conditions. However, in order to have confidence in the results of the models, a factorial-mixture design must be used to study the effect of temperature and nickel concentration. Moreover the models must be further tested and validated on the real samples from a plant. / AFRIKAANSE OPSOMMING: Hierdie werkstuk evalueer die gebruik van inverse kleinste kwadraatmetodes (IKK) en klassieke kleinste kwadraatmetodes (KKK) vir die kalibrasie van 'n diffuse reflektansiespektrofotometer vir die aanlyn monitering van die waterige fase in flottasieselle. Beer se wet word vir die kwantifisering van metale vir albei modelle gebruik. Die omskrewe data-gebaseerde modelle is op grond van voorspellingsvermoë vergelyk met'n. Blue Cube model, sodat die moontlike toepaslikheid van hierdie modelle bepaal kan word. 'n Diffuse reflectantie spektrofotometrie is ingespan vir die gelyktydige analise van koper (Cu), kobalt (Co) en sink (Zn) in oplossing. Eksperimentele analises is met behulp van 'n laboratoriumopstelling met 'n Blue Cube instrument uitgevoer. Die konsentrasies en matriks-samestellings van monsters is gesimuleer om Skorpion sinkmyn aanlegkondisies na te boots. Kalibrasie monsters is voorberei volgens . simpleks-sentroïed mengselontwerp met drievoudige sentroïede lopies. Onbekende (toets) monsters is ewekansig voorberei binne dieselfde konsentrasie spesifikasies as die kalibrasie monsters. Die invloed van temperatuur en nikkelkonsenstrasie op die absorpsie van die metale is in die bestek van 20 - 80 °C en 125 - 400 dpm, onderskeidelik, bepaal. Die data-gebaseerde modelle (IKK en KKK) is met sigbare en naby infrarooi (SNIR) spektra data van die kalibrasie monsters gekalibreer. 'n Gewysigde Beer metode is vir data voorbereiding benut om rou data na absorbansie waardes om te skakel. Die handgolflengte-seleksieprosedure is vir beide modelle gebruik om die golflengtes te kies. Die kwaliteit van die modelle is op grond van Rª en % wortel gemiddelde kwadratiese fout (WGKF) geevalueer, met waardes van 0.90 en 10% (onderskeidelik) as riglyne vir hierdie statistiese parameters. Beide IKK en KKK modelle het vir hul kalibrasie stappe vir al drie metale (Cu, Co en Zn) goeie resultate getoon. Dit is verder getoon dat albei modelle die slegste voorspellings lewer vir Zn (vergeleke met die ander metale) as gevolg van Zn se lae relatiewe intensiteit in die mengsel. Afgeleide ordes van absorbansie spektra is gebruik om die Zn voorspellings te versterk, maar het geen positiewe effek gehad nie; inteendeel, voorspellingakkuraatheid is verlaag. ʼn Verhoging in temperatuur het die intensiteite van die absorpsie spektra van alle metale verhoog, terwyl ʼn verhoging in nikkelkonsentrasie die voorspellingakkuraatheid van die modelle verlaag het. Die ontwikkelde data-gebaseerde modelle is met ʼn Blue Cube model vergelyk in terme van voorspellingsvermoë met behulp van variansie-analise (ANOVA). Die ANOVA resultate toon dat daar geen statistiese verskil tussen die ontwikkelde modelle en die Blue Cube model is nie, aangesien die F-waardes vir al die metale onder die kritiese F-waarde is. Die gedeeltelike kleinste kwadraatmodel (GKK) toon verder verhoogde voorspellingakkuraat-heid vir sinkmetaal tenoor beide die IKK en KKK modelle. Ten slotte, goeie ooreenstemming van die data-gebaseerde modelresultate met atoomabsorpsie spektroskopie (AAS) analise is vir die onbekende monsters gevind. Hierdie werkstuk toon dat die chemometriese modelle (IKK en KKK) wat hier ontwikkel is, gebruik kan word vir die kwantifisering van verskeie metale in werklike hidrometallurgiese oplossings, aangesien monsters gesimuleer is volgens aanlegkondisies. Om egter verdere vertroue te hê in die modelresultate, sal ʼn faktoriaal-mengselontwerp toegepas moet word om die effek van temperatuur en nikkelkonsentrasie te ondersoek. Voorts moet die modelle verder getoets en gevalideer word op werklike monsters van ʼn aanleg.

A proposta da presente tese foi desenvolver dispositivos inteligentes (língua e nariz eletrônicos/ colorimétrico) de baixo custo para discriminar amostras de alimentos contaminados quimicamente e biologicamente. Um dispositivo \"optoeletrônico\" à base de membranas poliméricas coloridas com indicadores de pH foi utilizado para discriminar compostos voláteis emitidos por micro-organismos (aminas liberadas pelos processos de deterioração dos alimentos e que são produto da descarboxilação de aminoácidos em alimentos predominantemente proteicos). As aminas avaliadas nesse estudo foram: isobutilamina, isopentilamina e trietilamina. O limite de detecção de 5 ppm das aminas foi alcançado utilizando o dispositivo \"optoeletrônico\" e, esse sistema, também foi testado em amostras reais de carne contaminadas obtendo uma boa discriminação das amostras com e sem as aminas. Aminas biogênicas (cadaverina, tiramina e putrescina) também foram testadas obtendo uma separação pelo gráfico de escores. Em uma segunda etapa o dispositivo também foi avaliado para discriminar quatro espécies de bactérias (Klebsiella pneumoniae, Proteus vulgaris, Proteus mirabilis e Escherichia coli) incubadas a 37°C e 25°C. Em ambos os casos o dispositivo inteligente utilizou um smartphone para registrar as imagens que atuou como detector para extração dos dados de RGB das imagens. A partir dessas informações (valores de RGB), as ferramentas quimiométricas PCA (do inglês Principal Component Analysis, Análise de Componentes Principais) e HCA (do inglês Hierarchical Cluster Analysis, Análise de Agrupamentos Hierárquicos) foram utilizadas para discriminar as amostras e a k-NN (do inglês kth Nearest Neighbor, k- vizinhos mais próximos) para validar o método. Em uma terceira etapa, uma língua eletrônica voltamétrica foi fabricada para discriminar amostras de leite adulteradas com melamina, ureia e formaldeído contendo concentrações finais de 0,95; 4,16 e 10,0 mmol L-1, respectivamente. Essa língua voltamétrica foi composta por três eletrodos metálicos: platina, ouro e cobre e dados voltamétricos foram utilizados como dados de entrada para as ferramentas quimiométricas (PCA e HCA). Foram testados três tipos de leite (integral, desnatado e semidesnatado) de três diferentes marcas e todos eles puderam ser discriminados com sucesso. O trabalho também apresenta a utilização de MIPs (polímeros molecularmente impressos - do inglês, molecularly imprinted polymers) como alternativa para detecção e discriminação de alimentos contaminados fazendo uso da impressão (cavidades) de substâncias químicas contaminantes ou das proteínas específicas de cada micro-organismo presente no processo de deterioração dos alimentos / The present thesis aimed at development of low cost smart devices (electronic tongue and colorimetric nose) to discriminate chemically and biologically contamination in food samples. An \"optoelectronic\" plastic-based device with colored membranes contained pH indicator was used to discriminate volatile compounds released by microorganisms, due to the deterioration process of protein in food by the organisms. The amines evaluated in this study were: isobutylamine, isopentylamine and triethylamine, achieving a detection limit of 5 ppm. Such system was also tested in real meat samples contaminated with individual amines obtained a good discrimination of samples with and without studied compounds. Biogenic amines (cadaverine, tyramine and putrescine) were also tested and discriminated. In a second step, the device was also evaluated to discriminate four bacteria species (Klebsiella pneumoniae, Proteus vulgaris, Proteus mirabilis and Escherichia coli) incubated at 37 ° C and 25 ° C. In both cases, a smartphone was used as detector to extract RGB values of the samples. From extracted information (RGB values), the chemometric tools PCA (Principal Component Analysis) and HCA (Hierarchical Cluster Analysis) were used to discriminate samples and k-NN (kth Nearest Neighbor) was evaluated to validate the method. In a third stage, a voltammetric electronic tongue was developed to discriminate adulterated milk samples with melamine, urea and formaldehyde. This voltammetric electronic tongue was fabricated using three working electrodes: platinum, gold and copper and the voltammetric data was used as input data for chemometric tools (PCA and HCA). Three types of milk (whole, skimmed and semi-skimmed) from three different brands were tested and all of them could be successfully discriminated

A proposta da presente tese foi desenvolver dispositivos inteligentes (língua e nariz eletrônicos/ colorimétrico) de baixo custo para discriminar amostras de alimentos contaminados quimicamente e biologicamente. Um dispositivo \"optoeletrônico\" à base de membranas poliméricas coloridas com indicadores de pH foi utilizado para discriminar compostos voláteis emitidos por micro-organismos (aminas liberadas pelos processos de deterioração dos alimentos e que são produto da descarboxilação de aminoácidos em alimentos predominantemente proteicos). As aminas avaliadas nesse estudo foram: isobutilamina, isopentilamina e trietilamina. O limite de detecção de 5 ppm das aminas foi alcançado utilizando o dispositivo \"optoeletrônico\" e, esse sistema, também foi testado em amostras reais de carne contaminadas obtendo uma boa discriminação das amostras com e sem as aminas. Aminas biogênicas (cadaverina, tiramina e putrescina) também foram testadas obtendo uma separação pelo gráfico de escores. Em uma segunda etapa o dispositivo também foi avaliado para discriminar quatro espécies de bactérias (Klebsiella pneumoniae, Proteus vulgaris, Proteus mirabilis e Escherichia coli) incubadas a 37°C e 25°C. Em ambos os casos o dispositivo inteligente utilizou um smartphone para registrar as imagens que atuou como detector para extração dos dados de RGB das imagens. A partir dessas informações (valores de RGB), as ferramentas quimiométricas PCA (do inglês Principal Component Analysis, Análise de Componentes Principais) e HCA (do inglês Hierarchical Cluster Analysis, Análise de Agrupamentos Hierárquicos) foram utilizadas para discriminar as amostras e a k-NN (do inglês kth Nearest Neighbor, k- vizinhos mais próximos) para validar o método. Em uma terceira etapa, uma língua eletrônica voltamétrica foi fabricada para discriminar amostras de leite adulteradas com melamina, ureia e formaldeído contendo concentrações finais de 0,95; 4,16 e 10,0 mmol L-1, respectivamente. Essa língua voltamétrica foi composta por três eletrodos metálicos: platina, ouro e cobre e dados voltamétricos foram utilizados como dados de entrada para as ferramentas quimiométricas (PCA e HCA). Foram testados três tipos de leite (integral, desnatado e semidesnatado) de três diferentes marcas e todos eles puderam ser discriminados com sucesso. O trabalho também apresenta a utilização de MIPs (polímeros molecularmente impressos - do inglês, molecularly imprinted polymers) como alternativa para detecção e discriminação de alimentos contaminados fazendo uso da impressão (cavidades) de substâncias químicas contaminantes ou das proteínas específicas de cada micro-organismo presente no processo de deterioração dos alimentos / The present thesis aimed at development of low cost smart devices (electronic tongue and colorimetric nose) to discriminate chemically and biologically contamination in food samples. An \"optoelectronic\" plastic-based device with colored membranes contained pH indicator was used to discriminate volatile compounds released by microorganisms, due to the deterioration process of protein in food by the organisms. The amines evaluated in this study were: isobutylamine, isopentylamine and triethylamine, achieving a detection limit of 5 ppm. Such system was also tested in real meat samples contaminated with individual amines obtained a good discrimination of samples with and without studied compounds. Biogenic amines (cadaverine, tyramine and putrescine) were also tested and discriminated. In a second step, the device was also evaluated to discriminate four bacteria species (Klebsiella pneumoniae, Proteus vulgaris, Proteus mirabilis and Escherichia coli) incubated at 37 ° C and 25 ° C. In both cases, a smartphone was used as detector to extract RGB values of the samples. From extracted information (RGB values), the chemometric tools PCA (Principal Component Analysis) and HCA (Hierarchical Cluster Analysis) were used to discriminate samples and k-NN (kth Nearest Neighbor) was evaluated to validate the method. In a third stage, a voltammetric electronic tongue was developed to discriminate adulterated milk samples with melamine, urea and formaldehyde. This voltammetric electronic tongue was fabricated using three working electrodes: platinum, gold and copper and the voltammetric data was used as input data for chemometric tools (PCA and HCA). Three types of milk (whole, skimmed and semi-skimmed) from three different brands were tested and all of them could be successfully discriminated

Submitted by Ricardo Cedraz Duque Moliterno (ricardo.moliterno@uefs.br) on 2015-07-27T21:18:33Z No. of bitstreams: 1 Dissertac?o Jos? Jorge Silva Junior.pdf: 3038189 bytes, checksum: be43dcbd4f764e08ab18fd95a388e950 (MD5) / Made available in DSpace on 2015-07-27T21:18:33Z (GMT). No. of bitstreams: 1 Dissertac?o Jos? Jorge Silva Junior.pdf: 3038189 bytes, checksum: be43dcbd4f764e08ab18fd95a388e950 (MD5) Previous issue date: 2014-07-31 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / Pests are responsible for high losses in cocoa production in Brazil and other countries, among them the witches' broom (WB) is one of the most important and destructive to the cocoa, even causing losses of up to 95% of production. This plague has spread very easily in the state of Bahia due to environmental conditions that provided the spread of WB, caused by the fungus Moniliophthora pernicious. Several chemical compounds have been tested in order to prevent or eradicate WB, however it has not showed good results, so the present study aimed to perform in silico assays were obtained in order to identify inhibitors of UDP-N-acetylglucosamine pyrophosphorylase (UNAcP) of M. perniciosa. For achieve this goal, computational methods have been employed in the search for new inhibitors for UNAcP where different stages of research and evaluation were performed. The initial stage of virtual screening consisted of the choice of the scoring function, thus the following scoring functions were evaluated: Broyden Fletcher Goldfarb Shanno (BFGS) present in AutoDock VINA 1.1.2; Grid and Grid Score Score+Hawkins GB/SA both present in DOCK 6.5 and calculate the consensus score. The results were analyzed by calculating Enrichment Factor (EF) analysis of the ROC curve and its respective Area under an ROC curve (AUC). The Grid Score presented EF(5)=7.85. The ROC curve analysis allowed us to observe that the Grid Score function can identify almost 40% of active molecules with less than 10% of the database (false positive and active molecules), AUC analysis demonstrated that the Grid Score has greater accuracy (AUC=0.87). Thus, these results showed what the Grid Score was the best scoring function for this system. A database composed of molecules derived from natural sources was also used. The top ten results of virtual screening of the DOCK6.5 underwent online platform ChemGPS-NP, for the calculation of chemical descriptors. Thus, the molecules were re-categorized, based on the values of the Grid Score DOCK6.5 and chemical descriptors ChemGPS-NP. The results indicate the ZINC68592326 molecule his the best score and the analysis indicates that this has hydrophobic interactions with Ala380, Gln113, Gly112, Gly381, Ser168, Arg383, Pro221 and hydrogen bond interaction (3.32?) with Asn224. The virtual screening database of molecules derived from natural products research allowed with a universe of structures with very different characteristics. It was possible to obtain molecules with great structural diversity between the top ranking, however, also found very similar to the reference molecules. The use of chemometric methods is considered very useful and allows a systematic and consistent choice of structures, mainly by taking into account chemical descriptors and molecular characteristics, allowing for a more detailed evaluation. / Pragas s?o respons?veis por elevadas perdas na produ??o de cacau no Brasil e no mundo, dentre elas a vassoura-de-bruxa (VB) ? uma das mais importantes e destrutivas para o cacaueiro, chegando a causar perdas de at? 95% da produ??o. Essa praga disseminou-se muito facilmente no estado da Bahia devido a condi??es ambientais que proporcionaram a propaga??o da VB, causada pelo fungo Moniliophthora perniciosa. Diversos compostos qu?micos v?m sendo testados com o objetivo de prevenir ou erradicar a VB, por?m n?o foram obtidos bons resultados, portanto, o presente trabalho teve como principal objetivo realizar ensaios in silico, a fim de identificar inibidores da UDP-N-acetilglicosamina pirofosforilase (UNAcP) do M. perniciosa. Para tanto, foram empregados m?todos computacionais na busca de novos inibidores para a UNAcP, onde foram realizadas diferentes etapas de busca e avalia??o. A etapa inicial da triagem virtual consistiu na escolha da fun??o de pontua??o, assim, foram avaliadas as seguintes fun??es de pontua??o: Broyden?Fletcher?Goldfarb?Shanno (BFGS) presente no AUTODOCK VINA 1.1.2; Grid Score e Grid Score+Hawkins GB/SA ambos presentes no DOCK 6.5 e o c?lculo do escore de consenso. Os resultados foram analisados atrav?s do c?lculo de Fator de Enriquecimento (FE), analise da curva ROC e sua respectiva ?rea Sobre a Curva (AUC). O Grid Score apresentou FE(5)=7,85. A an?lise da curva ROC permitiu observar que a fun??o Grid Score consegue identificar quase 40% das mol?culas ativas com menos de 10% do banco de dados (mol?culas ativas e falso positivos), a an?lise da AUC demonstrou que o Grid Score tem maior exatid?o (AUC=0,87). Assim os resultados da avalia??o apontaram o Grid Score como melhor fun??o de pontua??o para esse sistema. Foi utilizado um banco de dados composto por mol?culas oriundas de fontes naturais. Os dez melhores resultados da triagem virtual feita no DOCK6.5 foram submetidos ? plataforma on line ChemGPS-NP, para o c?lculo dos descritores qu?micos. Assim, as mol?culas foram recategorizadas, baseando-se nos valores do Grid Score do DOCK6.5 e descritores qu?micos do ChemGPS-NP. Os resultados apontaram a mol?cula ZINC68592326 com a melhor pontua??o, a an?lise das intera??es intermoleculares indica que est? mol?cula apresenta intera??es hidrof?bicas com os res?duos Ala380, Gln113, Gli112, Gli381, Ser168, Arg383, Pro221 e liga??o de hidrog?nio do tipo aceptora com dist?ncia de 3,32? com o res?duo Asn224. A triagem virtual em banco de dados de mol?culas oriundas de produtos naturais permitiu a investiga??o com um universo de estruturas com caracter?sticas muito diversas. Foi poss?vel obter mol?culas com grande diversidade estrutural entre os primeiros do ranking, por?m, foram encontradas tamb?m mol?culas muito similares ?s mol?culas de refer?ncia. A utiliza??o de m?todos quimiom?tricos, ? considerada muito ?til e permitem uma escolha sistem?tica e consistente das estruturas, principalmente por levar em considera??o, descritores qu?micos e caracter?sticas moleculares, permitindo uma avalia??o mais criteriosa.