Foram isoladas de Piper scutifolium e P. corcovadensis seis amidas, incluindo a piperovatina, piperlonguminina, isopiperlonguminina e corcovadina, duas inéditas (scutifoliamida A e scutifoliamida B), além de duas aristolactamas (piperolactama C e stigmalactama). A partir de P. tuberculatum foram isoladas as amidas piplartina e pelitorina e os ésteres (E)-3,4,5-trimetoxicinamato de etila (11) e 3,4,5- trimetoxidiidrocinamato de etila (12), esse último obtido pela primeira vez de origem natural. Em função da atividade biológica apresentada pelas amidas isoladas, foram sintetizadas 5-fenil-pentadienamidas e 3-cinamamidas com diferentes substituintes nos anéis aromáticos e na porção amídica. Os extratos, produtos naturais isolados e sintéticos foram submetidos a ensaios de atividade antifúngica frente Cladosporium cladosporioides e C. sphaerospermum, antimicrobiana frente à Candida albicans, C. krusei, C. parapsilosis e Cryptococcus neoformans, inibidora de acetilcolinesterase, carrapaticida frente à Boophilus microplus e citotóxica frente a linhagens tumorais humanas. Para a atividade antifúngica contra C. cladosporioides e C. sphaerospermum foi constatada maior atividade para as N-isobutil e N-pentilamidas sem substituintes no anel aromático. As N-isobutilamidas foram mais ativas como inibidores de acetilcolinesterase; contra B. microplus grande atividade foi apresentada por piperovatina, e os ensaios de citotoxicidade indicaram que o grupo 5,6-dihidropiridin- 2(1H)-ona é fundamental para a atividade. As plântulas de P. corcovadensis apresentaram em sua composição predominantemente piperovatina e assim foram utilizadas para estudos com incorporação de acetato de sódio-[1-14C] e L-fenilalanina - [U-14C] na mesma. As plântulas e calos obtidos para P. scutifolium não apresentaram produção significativa de metabólitos secundários. O estudo do metabolismo fenilpropanoídico de P. regnellii resultou no isolamento parcial da enzima responsável pela conversão de conocarpano em eupomatenóide-6. / Six amides were isolated from Piper scutifolium and P. corcovadensis including piperovatine, piperlonguminine, isopiperlonguminine and corcovadine, the new scutifoliamide A and scutifoliamide B and also two aristolactams (piperolactam C and stigmalactam). From P. tuberculatum the amides piplartine and pellitorine and two esters, ethyl (E)-3,4,5-trimethoxycinnamate (11) and ethyl 3,4,5- trimethoxydihydrocinnamate (12) were isolated, this last one obtained for the first time from natural sources. Due to the biological activity observed for the natural amides, 5- phenyl-pentadienamides and 3-cinnamamides having different substituents in the aromatic ring and amide moietis were synthesized. Extracts, isolated and synthetic compounds were assayed against Cladosporium cladosporioides, C. sphaerospermum, Candida albicans, C. krusei, C. parapsilosis and Cryptococcus neoformans, inhibitory of acetylcholinesterase, against the tick Boophilus microplus and citotoxic against human cell lines. A higher activity was observed against C. cladosporioides and C. sphaerospermum for N-isobutylamides and N-pentylamides having no substituents in the aromatic ring. N-isobutylamides were very active inhibitors of acetylcholinesterase; piperovatin was the most active against B. microplus and 5,6-dihydropyridin-2(1H)-one moiety was essential as the citotoxicity is concerned. Plantlets of P. corcovadensis contained piperovatine as major compound and thus were used as model for incorporation of sodium acetate-[1-14C] and L-phenylalanine-[U-14C]. The production of secondary metabolites in plantlets and callus of P. scutifolium was not significant. The studies of phenylpropanoid metabolism in P. regnellii was addressed to partial purification and characterization of the enzyme involved in the conversion of conocarpan to eupomatenoid-6.

As doenças parasitárias continuam sendo um sério desafio de saúde pública, principalmente em países subdesenvolvidos ou em desenvolvimento. Dentre as diversas parasitoses existentes, pode-se destacar a leishmaniose, endêmica em vários países localizados nas regiões tropicais e subtropicais do globo terrestre. Ainda hoje, milhões de pessoas adquirem a infecção e milhares vão a óbito devido às complicações da doença quando não diagnosticada e tratada corretamente. Pesquisas voltadas à busca de tratamentos mais efetivos e seguros de doenças consideradas de países que negligenciam tais são de suma importância, uma vez que a disponibilidade de medicamentos eficazes e seguros ainda é bastante limitada, além do setor da indústria farmacêutica não demonstrar disposição em investimentos. Diante destes fatos, o presente trabalho visou à obtenção de novos candidatos a protótipos de fármacos leishmanicidas, utilizando como modelo estrutural a piperina, uma amida natural com propriedades antileishmania. Assim, foram obtidos oito ésteres (LFQM 138-145), tendo em suas estruturas as subunidades benzodioxola e piperidínica, comuns à piperina (6). Além destes, dois carbamatos (LFQM 146 e LFQM 147) também foram obtidos. Todos os compostos foram elucidados estruturalmente por técnicas de espectrometria (IV, RMN e EM), além de avaliados biologicamente in vitro frente às formas promastigotas de Leishmania amazonensis através do IC50 em μM. As substâncias mais ativas da série dos ésteres foram LFQM 144, LFQM 145 e LFQM 139, com valores de IC50 de 41,06 μM, 42,83 μM e 51,58 μM, respectivamente. Para a série dos carbamatos, o mais ativo foi LFQM 146 com IC50 = 43,16 μM, sendo equipotente aos dois compostos ésteres mais ativos LFQM 144 e LFQM 145. Todos os compostos foram menos ativos que a anfotericina B (IC50 = 5,08 μM), utilizada como medicamento padrão nas análises. Os compostos mostraram baixo perfil de citotoxicidade ao serem avaliados pelo ensaio de MTT com monócitos humanos, sendo o éster LFQM 145 o mais seguro dentre todos os sintetizados, com relação CC50/IC50 = 40,10. Dessa forma, o perfil molecular destes compostos está sendo considerado de grande interesse, podendo levar através de otimizações estruturais futuras à descoberta de compostos mais ativos e seguros / Parasitic diseases remain a serious public health challenge, especially in underdeveloped or developing countries. Among the various existing parasitosis, we can highlight that leishmaniasis is endemic in many countries located in tropical and subtropical regions of the globe. Even today, millions of people become infected and thousands will die as result of complications of the disease if not diagnosed and treated properly. Researches aimed at seeking more effective and safer treatments for diseases considered countries that neglect these are of paramount importance, since the availability of effective and safe medicines is still quite limited and also the pharmaceutical industry sector not demonstrate willingness to investments. Given these facts, the present work aimed at obtaining new candidate prototypes antileishmanial drugs, using as structural model piperine, an amide with natural antileishmanial properties. Thus, we obtained eight piperidine-benzodioxole esters (LFQM 138-145) presenting in their structures the piperidinic and benzodioxolic subunits, common to the compound model, piperine (6). In addition, two carbamates (LFQM 146 and LFQM 147) were also obtained. All compounds had their structures elucidated by spectral techniques IR, NMR and MS. All compounds have been biologically evaluated in vitro against the Leishmania amazonensis promastigotes and values were expressed by IC50 in μM. The most active substances of the ester series were LFQM 144, LFQM 145 and LFQM 139, with IC50 values of 41.06 μM, 42.83 μM and 51.58 μM, respectively. For the carbamate series, the most active was LFQM 146 with IC50 = 43.16 μM, that was equipotent to the evaluated esters LFQM 144 and LFQM 145. All compounds were less active than amphotericin B (IC50 = 5.08 μM) that was used as standard drug in the analysis. The compounds showed low toxicity in the MTT human cell viability assay and LFQM 145 was considered the safer between all the synthetized compounds, with a relation CC50/IC50 = 40,10. Thus, the molecular profile of these compounds is being considered of great interest and may lead future structural optimizations through the discovery of compounds most active and safe / Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES

Submitted by Edisangela Bastos (edisangela@ufpa.br) on 2012-09-21T20:43:25Z No. of bitstreams: 2 license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Dissertacao_IsolamentoCaracterizacaoExpressao.pdf: 1351156 bytes, checksum: b4b77e8d0787e6b1ada62ef0472dda05 (MD5) / Approved for entry into archive by Ana Rosa Silva(arosa@ufpa.br) on 2012-09-28T17:47:55Z (GMT) No. of bitstreams: 2 license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Dissertacao_IsolamentoCaracterizacaoExpressao.pdf: 1351156 bytes, checksum: b4b77e8d0787e6b1ada62ef0472dda05 (MD5) / Made available in DSpace on 2012-09-28T17:47:55Z (GMT). No. of bitstreams: 2 license_rdf: 23898 bytes, checksum: e363e809996cf46ada20da1accfcd9c7 (MD5) Dissertacao_IsolamentoCaracterizacaoExpressao.pdf: 1351156 bytes, checksum: b4b77e8d0787e6b1ada62ef0472dda05 (MD5) Previous issue date: 2012-05 / CNPq - Conselho Nacional de Desenvolvimento Científico e Tecnológico / FAPESPA - Fundação Amazônia de Amparo a Estudos e Pesquisas / A pimenteira-do-reino (Piper nigrum L.) constitui uma das espécies de pimenta mais amplamente utilizadas no mundo, pertencendo à família Piperaceae, a qual compreende cerca de 1400 espécies distribuídas principalmente no continente americano e sudeste da Ásia, onde esta cultura originou. A pimenteira-do-reino foi introduzida no Brasil no século XVII, e tornou-se uma cultura de importância econômica desde 1933. O Estado do Pará é o principal produto brasileiro de pimenta-do-reino, contudo sua produção vem sendo afetada pela doença fusariose causada pelo fungo Fusarium solani f. sp. piperis. Estudos prévios revelaram a identificação de sequencias de cDNA diferencialmente expressas durante a interação da pimenteira-do-reino com o F. solani f. sp. piperis. Entre elas, uma sequencia de cDNA parcial que codifica para uma proteína transportadora de lipídeos (LTP), a qual é conhecida por seu importante papel na defesa de plantas contra patógenos e insetos. Desta forma, o objetivo principal deste trabalho foi isolar e caracterizar as sequencias de cDNA e genômica de uma LTP de pimenteira-do-reino, denominada PnLTP. O cDNA completo da PnLTP isolado por meio de experimentos de RACE apresentou 621 bp com 32 pb and 235 bp nas regiões não traduzidas 5‘ e 3‘, respectivamente. Este cDNA contem uma ORF de 354 bp codificando uma proteína deduzida de 117 resíduos de aminoácidos que apresentou alta identidade com LTPs de outras espécies vegetais. Análises das sequencias revelou que a PnLTP contem um potencial peptídeo sinal na extremidade amino-terminal e oito resíduos de cisteína preditos por formar quatro pontes de dissulfeto, as quais poderiam contribuir para a estabilidade desta proteína. O alinhamento entre as sequencias de cDNA e genômica revelou a ausência de introns na região codificante do gene PnLTP, o que está de acordo ao encontrado em outros genes de LTPs de plantas. Por último, a PnLTP madura foi expressa em sistema bacteriano. Experimentos adicionais serão realizados com o objetivo de avaliar a habilidade da PnLTP recombinante em inibir o crescimento do F. solani f. sp. piperis. / Black pepper (Piper nigrum L.) is one of the most widely used spices in the world belonging to the Piperaceae family, which comprises about 1400 species distributed mainly in the American tropics and Southern Asia, where this crop originated. Black pepper was introduced in Brazil in the 17th century and has been a nationally important crop since 1933. The Pará State is the main Brazilian producer of black pepper; however, the spice‘s production has been damaged by the root rot disease caused by Fusarium solani f. sp. piperis. Previous studies have revealed the identification of some cDNA sequences differentially expressed during compatible black pepper - F. solani f. sp. piperis interaction. Among them, a partial cDNA sequence coding for a putative Lipid transfer protein (LTP), which is know to play important roles in plant defense against insects and pathogens. Therefore, the aim of this work was to isolate and characterize the full-length cDNA and genomic sequences of black pepper LTP, named PnLTP. The PnLTP full-length cDNA isolated by RACE assays showed 621 bp with 32 bp and 235 bp non-coding sequences at the 5‘ and 3‘ ends, respectively. This cDNA contains a 354-bp ORF coding for a deduced protein with 117 amino acid residues that showed high identity with LTPs from different crops. Sequence analysis revealed that PnLTP contains a putative peptide signal at amino-terminal and eight cysteine residues predicted to form four disulfide bridges, which could contribute to protein stability. Alignment between genomic and cDNA sequences revealed no introns within PnLTP coding region, that is in accordance with other LTP plant genes. Finally, the mature PnLTP was expressed in bacteria system. Additional experiments will be performed in order to evaluate the ability of recombinant PnLTP in inhibit the F. solani f. sp. piperis growth.

Made available in DSpace on 2018-08-01T23:26:43Z (GMT). No. of bitstreams: 1 tese_11880_87 - Ana Carolina Lyra Brumat.pdf: 1982746 bytes, checksum: d2338d3f287ef07c150e9304247877f7 (MD5) Previous issue date: 2018-02-16 / O estudo espaço-temporal de doença de plantas analisa a interação entre o patógeno, ambiente e o hospedeiro, no qual existem diversas metodologias que podem ser utilizadas para esse fim. A fusariose é considerada a principal doença fúngica na cultura da pimenta-do-reino, no entanto ainda são poucos os estudos epidemiológicos da doença. Visto isso, objetivou-se com o trabalho estudar a distribuição espacial da fusariose em pimenta-do-reino utilizando diferentes metodologias de estudo. Foram monitoradas quatro áreas homogêneas de pimenta-do-reino, no município de São Mateus-ES, no período de dez/2015 a dez/2016. A presença ou ausência de sintomas, bem como a posição de cada planta, foram anotadas em planilhas obtendo-se o mapeamento da evolução da doença dentro das áreas. Para o estudo espacial analisou-se os dados por diferentes metodologias: Índice de Dispersão (ID), Lei de Taylor modificada, análise de dinâmica e estrutura de focos (ADEF), e a krigagem. A análise dos dados por meio Lei de Taylor modificada indicou distribuição agregada somente para a área quatro. A ADEF mostrou que, com a evolução da doença no campo, os focos se tornavam maiores e em menor número. Com a utilização de geoestatística foi possível observar que a fusariose é disseminada a curta distância, e que os focos obedecem a um padrão de alongamento. Comparando os resultados obtidos pelos diferentes métodos observa-se que a geoestatística corroborou com os resultados apresentados pelas metodologias convencionais (Lei de Taylor modificada e a ADEF), e que a mesma tem potencial para ser utilizada no estudo espacial de doença de plantas.

Submitted by Thais Lopes (th.lopes1598@gmail.com) on 2018-11-05T15:32:25Z No. of bitstreams: 3 Projeto do mestrado- oficial- Angela- 8-2.pdf: 3009718 bytes, checksum: 4c36b53edd59329e99ae4a5a353fe707 (MD5) ficha catalografica- 2.pdf: 5663 bytes, checksum: 4427a31cced13d1e8e4f0e666e047007 (MD5) CAPA -FINAL-OFICIAL-2.pdf: 785430 bytes, checksum: ee2c4bc693305e043627b35c6fd23d60 (MD5) / Approved for entry into archive by Marcos Roberto Gomes (mrobertosg@gmail.com) on 2018-11-05T17:57:52Z (GMT) No. of bitstreams: 3 Projeto do mestrado- oficial- Angela- 8-2.pdf: 3009718 bytes, checksum: 4c36b53edd59329e99ae4a5a353fe707 (MD5) ficha catalografica- 2.pdf: 5663 bytes, checksum: 4427a31cced13d1e8e4f0e666e047007 (MD5) CAPA -FINAL-OFICIAL-2.pdf: 785430 bytes, checksum: ee2c4bc693305e043627b35c6fd23d60 (MD5) / Approved for entry into archive by Divisão de Documentação/BC Biblioteca Central (ddbc@ufam.edu.br) on 2018-11-05T18:36:31Z (GMT) No. of bitstreams: 3 Projeto do mestrado- oficial- Angela- 8-2.pdf: 3009718 bytes, checksum: 4c36b53edd59329e99ae4a5a353fe707 (MD5) ficha catalografica- 2.pdf: 5663 bytes, checksum: 4427a31cced13d1e8e4f0e666e047007 (MD5) CAPA -FINAL-OFICIAL-2.pdf: 785430 bytes, checksum: ee2c4bc693305e043627b35c6fd23d60 (MD5) / Made available in DSpace on 2018-11-05T18:36:31Z (GMT). No. of bitstreams: 3 Projeto do mestrado- oficial- Angela- 8-2.pdf: 3009718 bytes, checksum: 4c36b53edd59329e99ae4a5a353fe707 (MD5) ficha catalografica- 2.pdf: 5663 bytes, checksum: 4427a31cced13d1e8e4f0e666e047007 (MD5) CAPA -FINAL-OFICIAL-2.pdf: 785430 bytes, checksum: ee2c4bc693305e043627b35c6fd23d60 (MD5) Previous issue date: 2018-08-24 / CAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível Superior / American Cutaneous Leishmaniasis (ACL) is considered a neglected disease and a public health problem. Its incidence has increased significantly in Brazil and in all continents. The current treatment is based on Glucantime®, as the first-choice drug, and Pentacarinat® and amphotericin B® as the second-choice drug. These drugs have disadvantages because they are injectable and with a high index of serious side effects, leading researchers to seek new pharmacological alternatives with more effectiveness, low cost and less invasion. Plants are promising sources of bioactive compounds and, through new technologies that allow modifications in the chemical structure of natural molecules, it is possible to synthesize new bioactive derivatives. The present study aimed to evaluate the antileishmanic effects of derivative dillapiol butyl ether (EBD), extracted from the leaves of Piper aduncum. The cytotoxic potential of EBD at serial concentrations of 500 to 15.62 μM in peritoneal macrophages of BALB/c mice for 48 h, and in RAW 264.7 macrophages for 72 h using Alamar Blue® dose-response method was evaluated. The antileishmanial activity of EBD was evidenced by the inhibition of viable forms of L. amazonensis promastigotes incubated at 25 ° C for 24, 48 and 72 hours when tested at 4.5 μM. The potential of EBD was evaluated at the concentration of 4.5 μM against amastigote forms internalized in peritoneal macrophages of mice, which were infected with promastigotes in a ratio of 5:1 and incubated for 24h to 48h. Regarding the selectivity index, this was determined by the effect of EBD on macrophages and promastigotes, according to a mathematical reason. In order to investigate the possible anthelmintic mechanism of EBD in macrophages for 24 and 48 h, a quantification of nitric oxide was performed in peritoneal macrophages and treated at different times. For the determination of reactive oxygen species (ROS), in peritoneal macrophages, a concentration of 4.5 μM was used and incubated together with DCFDA (Dichlorofluorescein Acetate) for 1, 3, 6, and 24 hours. The rate of infection in macrophages was determined by counting 100 infected cells under an optical microscope (1000x). Docking of EBD was carried out using protein of origin of the parasite (Leishmania) available in the database "Protein Data Bank" (PDB). There was no cellular cytotoxicity in peritoneal macrophages and RAW 264.7 with CC50 of 413 μM and 373.5, respectively, when exposed to EBD at the concentration of 500 μM to 15.62 μM for 24, 48 and/or 72 hours. EBD inhibited promastigote forms of L. amazonensis with an efficacy equal to Pentacarinat® for 72 hours with an IC50 of 1.6 μM and 2.2 μM, respectively. The selectivity index (SI) showed that EBD was more specific with a SI of 76.5 μM than Pentacarinat® with 8.7 μM. For the amastigote forms EBD presented an infection rate of 17% and 12%, dilapiol of 24% and 14% and Pentacarinat® of 10% and 9%. Molecular docking analysis of EBD demonstrated a binding energy of -7.8 by the site of action of U53 enzyme better than the parent compound. It is concluded that EBD derivative has antileishmania activity, being a promising dilapiol analogue for future in vivo tests. / A Leishmaniose Tegumentar Americana (LTA) é considerada uma doença negligenciada e um problema de saúde pública. Sua incidência tem aumentado significantemente no Brasil e em todos os continentes. O tratamento atual é a base de Glucantime®, tendo como fármaco de primeira escolha, a Pentacarinat® e anfotericina B® como fármaco de segunda escolha. Esses fármacos apresentam desvantagens por serem injetáveis e possuem elevados efeitos colaterais graves, levando aos pesquisadores buscar novas alternativas farmacológicas mais eficazes, de baixo custo e menos invasivos. As plantas são fontes promissoras de compostos bioativos, e por meio de novas tecnologias que permitam modificações na estrutura química de moléculas naturais pode sintetizar novos derivados bioativos. O presente estudo objetivou avaliar os efeitos antileishmania do derivado éter butil do dilapiol (EBD), extraído das folhas de Piper aduncum. Foi avaliado o potencial citotóxico do EBD nas concentrações seriadas de 500 a 15,62 μM em macrófagos peritoneais de camundongos BALB/c, por 48h e, em macrófagos RAW 264.7 por 72h, utilizando o método dose-resposta por Alamar Blue®. Para a atividade antileishmania do EBD, a 4,5 μM, evidenciou pela inibição as formas viáveis dos promastigotas de L. amazonensis, incubados a 25 ºC por 24, 48 e 72 horas. O potencial do EBD foi avaliada na concentração de 4,5 μM contra as formas amastigotas interiorizado em macrófagos peritoneais de camundongos, os quais foram infectados com promastigotas numa proporção de 5:1 e incubados por 24h a 48h. Quanto ao índice de seletividade (IS), este foi determinado pelo efeito do EBD sobre os macrófagos e promastigotas, conforme uma razão matemática. Para investigar o possível mecanismo antileshmania do EBD, em macrófagos durante 24 e 48 h, foi realizada uma quantificação de óxido nítrico em macrófagos peritoneais e tratados em tempos diferentes. Para a dosagem das espécies reativas de oxigênio (EROs), em macrófagos peritoneais, utilizou-se uma concentração de 4,5 μM, e foram incubados juntos ao DCFDA (Acetato de Diclorofluoresceína) por 1, 3, 6, e 24 horas. A taxa de infecção em macrófagos determinou-se pela contagem de 100 células infectadas em microscópio óptico (1000x). A docagem do EBD realizou-se utilizando proteína de origem do parasita (Leishmania) disponível no banco de dados “Protein Data Bank” (PDB). Não houve citotoxicidade celular em macrófagos peritoneais e RAW 264.7, com CC50 de 413 μM e 373,5 respectivamente, quando expostos ao EBD na concentração de 500 μM a 15,62 μM por 24, 48 e/ou 72 horas. O EBD, inibiu as formas promastigotas de L. amazonensis com uma eficácia igual a Pentacarinat® por 72 horas, com uma CI50 de 1,6 μM e 2,2 μM respectivamente. O índice de seletividade (IS), demonstrou que o EBD foi mais especifico, apresentando um IS de 76,5 μM do que a Pentacarinat® com 8,7μM. E, às formas amastigotas, o EBD apresentou uma taxa de infecção de 17% e 12%, dilapiol de 24% e 14% e Pentacarinat® de 10% e 9%. A análise por docagem molecular do EBD, demonstrou uma ligação de energia de -7,8 pelo sítio de ação da enzima U53, melhor do que o composto de origem. Conclui-se que o derivado EBD possui atividade antileishmania, sendo um análogo de dilapiol promissor para futuros testes in vivo.

The goal of this thesis was to understand and quantify to what extent plants are used for the treatment of mental and folk illnesses such as susto and mal aire in the Neotropics and to investigate the anxiolytic and antiepileptic potential of previously unstudied Neotropical members of the genera Piper and Peperomia. Firstly, the literature was reviewed and a regression analysis method was used in order to quantitatively determine which plant families are preferred for the treatment of mental, behavioral and neurological health disorders in the Neotropics. This analysis identified Piperaceae, among others, as an important taxonomic group for the treatment of such disorders. Following that lead, a botanical survey was conducted in Peru, where 47 species of Piperaceae and 21 plants traditionally used for folk illnesses by the Yanesha of Peru, an Amazonian ethnic group, were collected. In order to target potential anxiolytic and antiepileptic plants, two high throughput bioassays were used to evaluate the extracts’ in vitro activity on the γ-aminobutyric acid (GABA) system. Plant extracts in general demonstrated moderate to high affinity to the GABA-BZD receptor. Additionally, extracts demonstrated low to moderate activity in the inhibition of the GABA-T enzyme, with a few plants exhibiting promising activity. Plants selected by the Yanesha showed comparable activity to the other Piperaceae plants with Piper cremii being the most active plant in the GABAA assay, and Drymaria cordata in the GABA-T assay. Finally, four phytochemicals from Piper tuerckheimii, a plant regarded as one of the most effective traditional remedy for the treatment of epilepsy and susto by the Q’eqchi’ Maya of Belize presented, were isolated for the first time.

The goal of this thesis was to understand and quantify to what extent plants are used for the treatment of mental and folk illnesses such as susto and mal aire in the Neotropics and to investigate the anxiolytic and antiepileptic potential of previously unstudied Neotropical members of the genera Piper and Peperomia. Firstly, the literature was reviewed and a regression analysis method was used in order to quantitatively determine which plant families are preferred for the treatment of mental, behavioral and neurological health disorders in the Neotropics. This analysis identified Piperaceae, among others, as an important taxonomic group for the treatment of such disorders. Following that lead, a botanical survey was conducted in Peru, where 47 species of Piperaceae and 21 plants traditionally used for folk illnesses by the Yanesha of Peru, an Amazonian ethnic group, were collected. In order to target potential anxiolytic and antiepileptic plants, two high throughput bioassays were used to evaluate the extracts’ in vitro activity on the γ-aminobutyric acid (GABA) system. Plant extracts in general demonstrated moderate to high affinity to the GABA-BZD receptor. Additionally, extracts demonstrated low to moderate activity in the inhibition of the GABA-T enzyme, with a few plants exhibiting promising activity. Plants selected by the Yanesha showed comparable activity to the other Piperaceae plants with Piper cremii being the most active plant in the GABAA assay, and Drymaria cordata in the GABA-T assay. Finally, four phytochemicals from Piper tuerckheimii, a plant regarded as one of the most effective traditional remedy for the treatment of epilepsy and susto by the Q’eqchi’ Maya of Belize presented, were isolated for the first time.

The availability of complete plastid genomes has been playing an important role in resolving phylogenetic relationships among the major clades of land plants and in improving our understanding of the evolution of genomic organization. The increased availability of complete genome sequences has enabled researchers to build large multi-gene datasets for phylogenetic and molecular evolutionary studies. In chapter 2 of this thesis a web-based multiple sequence web viewer and alignment tool (MSWAT) is developed to handle large amount of data generated from complete genome sequences for phylogenetic and evolutionary analyses. We expect that MSWAT will be of general interest to biologists who are building large data matrices for evolutionary analyses. The third chapter presents the sequenced plastid genomes of three magnoliids, Drimys (Canellales), Liriodendron (Magnoliales), and Piper (Piperales). Data from these genomes, in combination with 32 other angiosperm plastid genomes, were used to assess phylogenetic relationships of magnoliids to other angiosperms and to examine patterns of variation of GC content. Evolutionary comparisons of three new magnoliid plastid genome sequences, combined with other published angiosperm genomes, confirm that GC content is unevenly distributed across the genome by location, codon position, and functional group. Furthermore, phylogenetic analyses provide the strongest support so far for the hypothesis that the magnoliids are sister to a large clade that includes both monocots and eudicots. The fourth chapter presents the Trifolium subterraneum plastid genome sequence, which is unusual in genome size and organization relative to other angiosperm plastid genomes. The Trifolium plastid genome is an excellent model system to examine mechanisms of rearrangements and the evolution of repeats and unique DNA. / text

The goal of this thesis was to understand and quantify to what extent plants are used for the treatment of mental and folk illnesses such as susto and mal aire in the Neotropics and to investigate the anxiolytic and antiepileptic potential of previously unstudied Neotropical members of the genera Piper and Peperomia. Firstly, the literature was reviewed and a regression analysis method was used in order to quantitatively determine which plant families are preferred for the treatment of mental, behavioral and neurological health disorders in the Neotropics. This analysis identified Piperaceae, among others, as an important taxonomic group for the treatment of such disorders. Following that lead, a botanical survey was conducted in Peru, where 47 species of Piperaceae and 21 plants traditionally used for folk illnesses by the Yanesha of Peru, an Amazonian ethnic group, were collected. In order to target potential anxiolytic and antiepileptic plants, two high throughput bioassays were used to evaluate the extracts’ in vitro activity on the γ-aminobutyric acid (GABA) system. Plant extracts in general demonstrated moderate to high affinity to the GABA-BZD receptor. Additionally, extracts demonstrated low to moderate activity in the inhibition of the GABA-T enzyme, with a few plants exhibiting promising activity. Plants selected by the Yanesha showed comparable activity to the other Piperaceae plants with Piper cremii being the most active plant in the GABAA assay, and Drymaria cordata in the GABA-T assay. Finally, four phytochemicals from Piper tuerckheimii, a plant regarded as one of the most effective traditional remedy for the treatment of epilepsy and susto by the Q’eqchi’ Maya of Belize presented, were isolated for the first time.

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