Thesis (Ph. D.)--Rutgers University, 2008. / "Graduate Program in Pharmaceutical Science." Includes bibliographical references (p. 98-107).

Thesis (M.S.)--Worcester Polytechnic Institute. / Keywords: CTL; dengue. Includes bibliographical references (p. 57-64).

Thesis (Ph. D.)--University of Hong Kong, 2009. / Includes bibliographical references (leaves 194-237) Also available online.

Thesis (Ph.D.)--Texas Christian University, 2006. / Title from dissertation title page (viewed Sept. 12, 2006). Includes abstract. Includes bibliographical references.

Thesis (Ph. D.)--School of Pharmacy and Dept. of Chemistry. University of Missouri--Kansas City, 2004. / "A dissertation in pharmaceutical sciences and chemistry." Advisor: Ashim K. Mitra. Typescript. Vita. Description based on contents viewed Feb. 22, 2006; title from "catalog record" of the print edition. Includes bibliographical references (leaves 156-188). Online version of the print edition.

Thesis (M.Sc.)--York University, 2005. Graduate Programme in Biology. / Typescript. Includes bibliographical references (leaves 88-93). Also available on the Internet. MODE OF ACCESS via web browser by entering the following URL: http://gateway.proquest.com/openurl?url%5Fver=Z39.88-2004&res%5Fdat=xri:pqdiss &rft_val_fmt=info:ofi/fmt:kev:mtx:dissertation&rft_dat=xri:pqdiss:MR11797

Thesis (Ph.D.)--University of Minnesota, 1999. / Includes bibliographical references. Also available on the World Wide Web as a PDF file.

Made available in DSpace on 2015-04-09T12:28:11Z (GMT). No. of bitstreams: 0 Previous issue date: 2015-02-03Bitstream added on 2015-04-09T12:48:03Z : No. of bitstreams: 1 000819717.pdf: 4373541 bytes, checksum: a3af0e5e013e89194ce284da000b37a0 (MD5) / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) / A leishmaniose tegumentar possui ampla distribuição mundial, segundo dados da Organização Mundial da Saúde (OMS) e estima-se que haja o surgimento de 500 mil a um milhão de casos por ano. Segundo dados do Departamento de Informática do Sistema Único de Saúde (DATASUS), no ano de 2005 registraram-se mais de 180 milhões de casos de leishmaniose tegumentar no Brasil. Apesar da existência de tratamentos disponíveis, a cura da leishmaniose é um processo complexo, em virtude das dificuldades na administração dos fármacos injetáveis, dos inúmeros efeitos adversos e da toxicidade hepática, renal e cardíaca. Dessa forma o desenvolvimento de novos fármacos mais eficazes e menos tóxicos torna-se urgente. O bioisosterismo é uma ferramenta de modificação molecular que visa à obtenção de novos análogos com a mesma atividade biológica. Assim, tem sido utilizado na pesquisa de novos fármacos, buscando a melhoria na eficácia e segurança no tratamento de diversas doenças. O nitrofural (NF), 5-nitro-2-furaldeído semicarbazona, é um fármaco utilizado como antimicrobiano de uso tópico em vários tipos de lesões de pele, que apresenta atividade descrita contra formas amastigotas de L. donovani, L. enriettii e L. major. Baseando-se nas diversas atividades do fármaco, o trabalho proposto objetivou a síntese de bioisósteros de nitrofural e avaliação dos compostos quanto à atividade leishmanicida in vitro. Foram sintetizados e caracterizados através de métodos analíticos oito compostos, sendo um inédito. Sete deles foram avaliados quanto à atividade biológica frente às formas amastigotas de L.amazonensis, através do ensaio de MTT (brometo de 3-metil[4,5-dimetiltiazol-2-il]-2,5 difeniltetrazólio). O composto Lapdesf-MetSFS (8) apresentou atividade comparável à da pentamidina, fármaco padrão utilizado na terapêutica. / Cutaneous leishmaniasis is a world widely distributed disease and it is estimated, by the World Health Organization (WHO), the incidence of 500,000 to one million cases per year. According to the Department of the Unified Health System (DATASUS), in 2005 it was registered more than 180 million cases of cutaneous leishmaniasis in Brazil. Although treatments for leishmaniasis are available, it is a complex process, because of difficulties in administration, once the majority of the drugs are injectable, the several numbers of adverse effects, and liver, renal and cardiac toxicity. Due to that, the development of more effective and less toxic drugs becomes urgent. The bioisosterism is a molecular modification strategy that aims to obtain new analogues with the same biological activity. It has been used in the research for new drugs, in order to improve the effectiveness and safety in the treatment of various diseases. The nitrofural (NF) 5-nitro-2-furaldehyde semicarbazone, is a drug used as topical antimicrobial in various types of skin lesions is described which has activity against L. donovani, L. enriettii and L. major amastigote forms. Based on the various drug activities, the proposed work aimed the synthesis of bioisosters of nitrofural and evaluation of compounds for in vitro leishmanicidal activity. Were synthesized and characterized via analytical methods eight compounds, one unpublished. Seven of them were evaluated for biological activity against the amastigotesn forms of L. amazonensis by MTT assay (3-methyl bromide [4,5-dimethylthiazol-2-yl] -2,5-diphenyltetrazolium bromide). The Lapdesf-MetSFS (8) compound showed activity comparable to that of pentamidine, standard drug used in therapy.

M.Sc. / To successfully intervene in the HIV/AIDS pandemic, knowledge of the pathogenesis of the disease and factors that stimulate or inhibit viral replication are crucial. Plants are expected to produce antiviral compounds since viruses form one of the major groups of plant pathogens. The objective in this project was to investigate the effects of 6 plant extracts on immune responses as well as evaluate their potential anti-HIV activity. Plant species tested were: Hypoxis hemerocal/idea, Elephantorrhiza elephantina, Spirulina platensis, Echinacea purpurea, Echinacea pal/ida and Cannabis sativa. Extracts were prepared via 24 hour extraction or 12 hour reflux in H20, methanol and ethanol in a 1:5 ratio. The crude extracts were analysed by TLC and HPLC and shown to consist of complex related mixtures of compounds. Using LC-MS, partial identification of methanol extracts revealed the following expected compounds: 9- octadecenoic acid (E)- in Hypoxis hemerocallidea, 4H-1-benzopyran-4-one,2-(3,4- dihydroxyphenyl)-7 -(13-D-glucopyranosyloxy)-5-hydroxy- in E/ephantorrhiza e/ephantina, ethanol,2-butoxy-,phosphate in Spirulina platensis, 2-propenoic acid,3-(3,4-dihydroxyphenyl)- in Echinacea purpurea, 2-propenoic acid,3-(3,4-dihydroxyphenyl)- in Echinacea pal/ida and ~-9- tetrahydrocannabivarin in Cannabis sativa tincture. Viability assays using tetrazolium salts (XTT) gave a qualitative picture of events allowing us to assess host cell responses and extract toxicity. Extracts exhibited intrinsic absorbances at some visible wavelengths but did not interfere at the wavelengths used in this viability assay. Having analysed cell viability it was thought prudent to report on the type of cell death induced by either HIV or the extracts, so Annexin-V (indicator of apoptosis) and PI (indicator of necrosis) detected by flow cytometry was employed. Results obtained revealed that cells were driven towards necrosis rather than apoptosis. None of the extracts showed significant in vitro toxicity in CEMss, CEMNKR. U937, Jurkat and PM1 cells or ex vivo in PBMC at a concentration range of 1000f..lg/ml-4f.!g/ml. Viability assays were also an indirect indication of HIV's effect on the cells. As for the effect of extracts on the immune system, IL-2 secretion was stimulated by most of the extracts. The effect of plant extracts on HIV activity was also investigated by looking at core protein levels (p24 was generally decreased by methanol extracts), reverse transcriptase activity (no detectable influence) and envelope glycoprotein levels (gp120 levels were only marginally reduced). It appears that Echinacea purpurea, Echinacea pal/ida and Spirulina platensis have immune enhancing abilities, while Hypoxis hemerocallidea, Elephantorrhiza e/ephantina and Cannabis sativa have dual purposes by enhancing both immunity and inhibiting HIV activity.

The acquired immunodeficiency syndrome (AIDS) in humans, which is caused by the human immunodeficiency virus type 1 (HIV-1) remains among the leading causes of death worldwide. Although HAART has reduced HIV mortality significantly, adhering to the recommended drug schemes, significant toxicities experienced by treated patients, and the high mutation rate of the virus that seem to easily circumvent the action of these drugs emphasize the need for alternative treatment strategies. Medicinal plants are a good source for the discovery of novel antimicrobial chemotherapeutic agents. Reverse transcription is the most essential step for viral replication to succeed successfully. This makes reverse transcriptase the prime target for antiviral therapy against HIV. Emphasis was placed on the discovery of plants with inhibitory activity against HIV-1 reverse transcriptase. Crude extracts from the active plant(s) was screened in vitro for their ability to suppress HIV replication in suitable cell systems. The potential of isolating and identifying the active principle(s) was also investigated. Crude extracts from different parts of Gunnera perpensa showed similar amounts of inhibition: aqueous extracts (97% „b 0.110%SD), methanol/chloroform extracts (94% „b 2.374%SD), rhizome extracts (96% „b 0.475%SD), stem extracts (94% „b 3.723%SD), leaf extracts (96% „b 1.097% SD). Crude extracts were found to be significantly (P„T0.027) non-toxic to CEM.NKR.CCR5 cells and PBMCs at 5 ƒÝg/ml. In acutely infected CEM.NKR.CCR5 cells, acutely infected PBMCs, and chronically infected PBMCs Gunnera perpensa extracts did not significantly (P>0.05) increase cell viability or reduced HIV core protein content, over 4 days. The in vitro test did therefore not reflect the findings with the reverse transcriptase assay. Activity-guided fractionations of Gunnera perpensa rhizome extract lead to the collection of a significantly active fraction. NMR studies revealed the presence of an epimeric mixture of glucose ¡§contaminants¡¨ in this active fraction. The presence of these ¡§contaminants¡¨ concealed the true structure of the active principle. Gunnera perpensa was identified as containing a potential active principle that significantly inhibits recombinant HIV reverse transcriptase. Unfortunately, in vitro experiments could not confirm this finding. The identity and structure of the active principle remains unidentified. Future studies will be concerned with in vitro antiviral studies of the pure active principle. Furthermore, preliminary tests indicated that some of the original collection of crude extracts had anti-bacterial and anti-malarial activities. These findings can be investigated in future. / Dr. D. Meyer