No description available.

Made available in DSpace on 2016-08-10T10:29:40Z (GMT). No. of bitstreams: 1 Marlene Neves Antunes.pdf: 10408234 bytes, checksum: c1e51577817677c6ded3b53d4a4bbb59 (MD5) Previous issue date: 2009-11-05 / The medicinal plants have been a rich source for obtaining bioactive molecules, constituting one of the most successful strategies in the discovery of novel medicines. The specie Cochlospermum regium (Martius and Schrank) Pilger (Bixaceae), popularly known as algodãozinho-do-campo is a native plant, abundant in Brazilian Cerrado. After an ethnobotanical and ethnopharmacological research carried out at Tocantins State it was showed that this plant is used in folk medicine to treat several illnesses. Among the therapeutic indications the most frequents are: gynecological and renal inflammations, prostatitis, a few kinds of pains, fever, gastritis and skin affections, among others. This study aimed to contribute to the knowledge of the chemical constituents of C. regium. For this, extracts solutions were obtained by an exhausting way maceration of this plants roots in the solvents: hexane, dichloromethane, ethyl acetate and methanol, in this sequence increasing polarity, obtaining the following income rude mass macerated: 1,78%, 0,23%; 0,51% and 12,16%, respectively. The phytochemical investigation of the hexane extract (CrRH) allowed the isolation of substance initially identified as SA (7,0 mg), an unpublished chemical compound, still in characterization process and Substance SB (20,0 mg), identified as excelsina, a lignan reported for the first time in this specie. From the CrRH1 fraction originated by the fractionating chromatography column of the hexane extract was isolated the substance SC (6,0 mg) identified as a steroid, still in structural elucidation. From the dichloromethane extract (CrRD) the substance SD (9,0 mg) was isolated and identified as phidroxicinamic acid stereate, whose structures are not yet fully defined. Data obtained so far indicate the existence of a mixture of p-hidroxicinâmic acids, probably varying the size of the side chain ester. On the fractionation of ethyl acetate extract was obtained the substance SE (23mg) originated from the CrRAc1 fraction and identified as naringenin, a common flavanone in the genus Cochlospermum, have been also isolated in the stalk bark of this specie, not having, however, reports the presence of this flavanone in roots of C. regium. And finally, the SF substance (15,0 mg), originated of the CrRAc2 fraction, which was also identified as excelsina. / As plantas medicinais têm sido uma rica fonte para obtenção de moléculas bioativas, constituindo-se numa das mais bem sucedidas estratégias na descoberta de novos medicamentos. A espécie Cochlospermum regium (Martius e Schrank) Pilger (Bixaceae), popularmente conhecida como algodãozinho-do-campo, é uma planta nativa, abundante no cerrado brasileiro. No Tocantins, levantamento etnobotânico e etnofarmacológico realizado demonstrou que esta planta é utilizada na medicina popular no tratamento de várias enfermidades. Entre as indicações terapêuticas mais freqüentes estão: inflamações ginecológicas e renais, prostatites, dores diversas, febre, gastrite e afecções de pele, entre outras. Assim, este trabalho teve como objetivo contribuir para o conhecimento dos constituintes químicos de C. regium. Para tanto, foram obtidos extratos macerando-se diretamente, de forma exaustiva, as raízes da espécie nos solventes hexano, diclorometano, acetato de etila e metanol, nesta seqüência crescente de polaridade, obtendo-se o seguinte rendimento da massa bruta macerada: 1,78%, 0,23%; 0,51% e 12,16%, respectivamente. A análise fitoquímica do extrato hexano (CrRH) permitiu o isolamento das substâncias identificadas inicialmente como SA (7,0mg), composto inédito, ainda em processo de caracterização e Substância SB (20,0 mg), identificada como excelsina, uma lignana reportada pela primeira vez nesta espécie. Da fração CrRH1 proveniente do fracionamento cromatográfico do extrato hexânico, isolou-se a substância SC (6,0 mg) identificada como esteróide, ainda em fase de elucidação estrutural. Do extrato diclorometânico (CrRD) foi isolada a substância SD (9,0 mg), identificada como ácido p-hidroxicinâmico estereato, cuja estrutura ainda não está totalmente definida. Dados obtidos até o momento apontam a existência uma mistura de ácidos p-hidroxicinâmicos, provavelmente variando o tamanho da cadeia lateral do éster. Do fracionamento do extrato acetato de etila obteve-se a substância SE (23mg) originada da fração CrRAc1 e identificada como naringenina, flavanona comum no gênero Cochlospermum, tendo sido isolada, também, na casca do caule desta espécie, não havendo, entretanto, relatos da presença desta flavonona em raiz de C. regium. E finalmente, a substância SF (15,0 mg) originada da fração CrRAc2, que também foi identificada como excelsina.

No description available.

Depuis quelques décennies, les bactéries pathogènes multi-résistantes aux antibiotiques sont de plus en plus répandues dans le monde. Cette situation a suscité le besoin et l'intérêt de trouver des médicaments antibactériens avec de nouvelles cibles potentiels. La découverte des systèmes de communication de type quorum sensing (QS) régulant la virulence bactérienne représente une des cibles privilégiées pour contrôler les bactéries pathogènes autrement qu’en interférant avec leur croissance bactérienne. Dans l’écosystème naturel, un grand nombre d'organismes (Eucaryotes et Procaryotes) co-existent en synthétisant chacun de leur côté des métabolites secondaires. Les plantes, étant en permanence en contact avec des bactéries, synthétisent des métabolites secondaires capables d’inhiber l’expression des gènes de virulence chez les bactéries sans pour autant affecter ni leur croissance ni leur viabilité. Notre objectif a été de contribuer à la valorisation de la biodiversité malgache en identifiant des plantes et en y isolant les composés actifs présentant une capacité à perturber le mécanisme de QS chez P. aeruginosa PAO1, une bactérie pathogène opportuniste de l’homme, des animaux et des plantes. Dans ce but, nous avons tout d’abord réalisé un criblage d’activité anti-QS de différents flavonoïdes commerciaux. De ce criblage, la narigenine et la naringine ont été sélectionnées pour être les molécules de contrôle positif et négatif des tests d’activité anti-QS, respectivement. Par la suite, 4 espèces de Dalbergia endémique de Madagascar ont fait l’objet de criblage pour leur activité anti-QS. Ce travail a fait ressortir l’activité anti-QS très intéressante de l’écorce de D. trichocarpa à partir de laquelle nous avons isolée le composé actif nommé la coumarate de l’aldéhyde-oléanolique (OALC). Le contrôle naringénine et l’OALC ne présente aucun effets inhibiteurs sur la croissance bactérienne de P. aeruginosa PAO1 et sur l’expression du gène QS-indépendant aceA suggérant une activité d’inhibition spécifiquement liée au QS. Cependant, ces deux molécules présentent des spectres d’inhibition différente. En effet, les deux molécules diffèrent dans le sens que la naringenine n’inhibe pas l’expression du gène gacA et la motilité de type twitching contrairement à l’OALC. Ces résultats suggèrent que l’OALC et la naringénine représente des candidats potentiels pour des investigations in vivo quant à leur effet anti-QS et anti-biofilm sur des modèles infectieux d’organismes supérieurs. Par ailleurs, ils démontrent la richesse des plantes malgaches comme sources de nouvelles molécules anti-virulence ainsi que l’importance de telle investigation afin de renforcer notre arsenal thérapeutique en composé antibactérienne dans la lutte continuelle contre les bactéries pathogènes/Since few decades, multidrug resistant bacteria spread all over the world. This situation gives rise to the need and interest in finding antibacterial drugs with novel potent target. Discovery of communication system termed Quorum Sensing (QS) which regulate bacterial virulence factor represent privileged target in another way than interfering with bacterial growth. In natural ecosystem, many organisms (Eukaryotes and Prokaryotes) produce secondary metabolites. As plants are permanently in contact with bacteria, they have synthetized secondary metabolites which inhibit bacterial virulence gene expression without affecting bacterial viability. Our goal was to contribute to the valorization of Malagasy biodiversity and specifically to identify plants and isolate bioactive compound presenting ability to disrupt QS mechanism in P. aeruginosa, opportunistic pathogen bacteria in plants, animals and human. In this purpose, screening of commercial available flavonoids has been firstly carried out. From this screening, naringenin and naringin have been selected to be used as positive and negative QS inhibitor controls, respectively. Subsequently, Four Malagasy endemic Dalbergia species have been screened for their anti-QS activity. This work pointed out the interesting anti-QS activity of D. trichocarpa bark extract which led to the isolation of oleanolic aldehyde coumarate (OALC) as one major bioactive compound. At the concentration tested, naringenin and OALC did not affect P. aeruginosa PAO1 viability and didn’t reduce QS-independent aceA gene expression suggesting a specific anti-QS activity. However, these two compounds present different inhibition spectrum. Indeed, naringenin didn’t inhibit gacA gene expression and twitching motility contrarily to OALC. These results suggest that OALC and naringenin represent potent candidates for in vivo investigations in their anti-QS and anti-biofilm activity onto eukaryotes infectious model. Besides, this finding demonstrated the potent source for novel anti-virulence compounds of Malagasy flora and the importance of this kind of research to strengthen our antimicrobial therapeutic arsenal with the ongoing struggle against bacterial infection. / Doctorat en Sciences / info:eu-repo/semantics/nonPublished