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Alzheimer’s disease has about 9.9 million new cases annually, according to World Health Organization. Due to the increasing incidence of people affected by AD and the absence of an efficient treatment or cure so far, many researchers worldwide are involved in the search for novel promising drugs candidates, through several targets, exploring distinct structural patterns. In this context, we describe herein, focusing the last 20 years, strategic examples of substances with targets related to Alzheimer’s disease derived from natural products, such as alkaloids, chalcones, coumarins and flavonoids, in addition to carbamates and heterocyclic compounds. Furthermore, some cases are discussed where computational chemistry is used to better understand protein-ligand interactions.

Submitted by SUELY DA SILVA null (suelysilva0712@hotmail.com) on 2018-03-22T21:58:38Z No. of bitstreams: 1 Dissertação.pdf: 2325490 bytes, checksum: 74f21e908a95b780f73762e52893f2f5 (MD5) Rejected by Elza Mitiko Sato null (elzasato@ibilce.unesp.br), reason: Solicitamos que realize correções na submissão seguindo as orientações abaixo: Problema 01) Falta a FICHA CATALOGRÁFICA (Obrigatório pela ABNT NBR14724) Problema 0) O arquivo contém página em branco (PAG. 50), a mesma deve retirada; o arquivo não pode conter páginas em branco. Problema 03) A ordem das páginas pré-textuais estão incorretas, páginas pré-textuais (capa, folha de rosto, ficha catalográfica, folha de aprovação, dedicatória, agradecimentos, epígrafe, resumo na língua vernácula, resumo em língua estrangeira, listas de ilustrações, de tabelas, de abreviaturas, de siglas e de símbolos e sumário). Na página da Seção de pós-graduação, em Instruções para Qualificação e Defesas de Dissertação e Tese, você pode acessar o modelo das páginas pré-textuais. Lembramos que o arquivo depositado no repositório deve ser igual ao impresso. Agradecemos a compreensão. on 2018-03-23T14:49:52Z (GMT) Submitted by SUELY DA SILVA null (suelysilva0712@hotmail.com) on 2018-03-26T00:08:35Z No. of bitstreams: 1 Dissertação Versão para submissão.pdf: 2149985 bytes, checksum: 858e89c783eb406628e3751220daa809 (MD5) Approved for entry into archive by Elza Mitiko Sato null (elzasato@ibilce.unesp.br) on 2018-03-28T18:33:08Z (GMT) No. of bitstreams: 1 silva_s_me_sjrp_par.pdf: 939698 bytes, checksum: 953944463e92d4975844a37b93e04f6e (MD5) Made available in DSpace on 2018-03-28T18:33:08Z (GMT). No. of bitstreams: 1 silva_s_me_sjrp_par.pdf: 939698 bytes, checksum: 953944463e92d4975844a37b93e04f6e (MD5) Previous issue date: 2018-03-05 Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) A febre Zika é uma arbovirose resultante da infecção pelo vírus Zika (ZIKV). Em 2016 o ZIKV foi considerado pela Organização Mundial da Saúde um grave problema da saúde pública, devido ao número de casos de má formação congênita e distúrbios neurológicos vinculados à infecção, como microcefalia e síndrome de Guillain-Barré. Não existe atualmente antiviral específico contra o ZIKV. Neste contexto, torna-se necessário a busca por um antiviral seguro e que trate a infecção. Compostos naturais e seus derivados sintéticos vêm contribuindo significativamente para desenvolvimento de novos fármacos e têm ganhado destaque como potenciais antivirais, tornando-se uma possibilidade para o tratamento de infecções causadas pelo ZIKV. Sendo assim, o presente trabalho teve como objetivo avaliar os efeitos de compostos naturais e análogos sintéticos obtidos com base em estruturas químicas naturais no ciclo replicativo do ZIKV in vitro. Um total de 166 compostos dentre eles, flavonoides, alcaloides (naturais e sintéticos) e derivados do ácido antranílico foram analisados quanto à atividade antiviral pela infecção e tratamento de células Vero. Os dados obtidos mostraram que o composto sintético FAM E3, da classe diarilaminas derivadas do ácido antranílico (FAMs), inibiu um mínimo de 99.92% a etapa de replicação viral. Ensaios adicionais mostraram que o potencial de inibição é dose-dependente e este composto não apresenta ação antiviral na etapa de entrada do ciclo viral. Para elucidar o mecanismo de ação, investigamos a capacidade de FAM E3 em intercalar em dsRNA e inibir a polimerase viral. Os resultados mostraram que o composto não atua nessas vias. Ensaio de docking molecular sugerem que FAM E3 apresenta alta afinidade com a helicase NS3 e o complexo NS2B3NS3, sugerindo estas proteínas como possíveis alvos do composto. Outras análises são necessárias para estabelecer o mecanismo de ação do FAM E3, contudo este composto apresenta potencial terapêutico para o tratamento da febre Zika. Zika fever is an arboviruses resulting from infection cause by Zika virus (ZIKV). In 2016 the ZIKV was considered by the World Health Organization a serious public health problem due to the number of cases of congenital malformation and neurological disorders linked to infection, such as microcephaly and Guillain-Barré syndrome. There is no specific antiviral against infection ZIKV. In this context, it becomes necessary to search for a safe antiviral to treat this infection. Therefore molecules derived from natural sources and their synthetic analogues are a potential alternative for the investigation of active compounds to treat the infection. Natural compounds and their synthetic derivatives have contributed significantly to the development of new drugs and have been acquiring a high profile as potential antivirals, becoming a possibility for the treatment of infections caused by ZIKV. Thus, the present work had as objective to evaluate the effects of natural compounds and synthetic analogues obtained based on natural chemical structures in the replicative cycle of ZIKV in vitro. A total of 166 compounds among them, flavonoids, alkaloids (natural and synthetic) and anthranilic acid derivatives were analyzed for antiviral activity by infection and treatment of Vero cells. The data obtained showed that the synthetic compound FAM E3, from the class diarylamines derived from anthranilic acid (FAMs), inhibited a minimum of 99.92% of the viral infection. Additional assays have shown that the inhibition potential is dose-dependent and this compound does not present antiviral action at the entry stage of the viral cycle. To elucidate the mechanism of action, we investigated the ability of FAM E3 to intercalate into dsRNA and inhibit viral polymerase. The results showed that the compound does not act in these pathways. Molecular docking assay suggests that FAM E3 exhibits high affinity with the NS3 helicase and the NS2B3-NS3 complex, suggesting these proteins as possible targets of the compound. Other analyzes are needed to establish the mechanism of action of FAM E3, however this compound has therapeutic potential for the treatment of Zika fever.

Submitted by Guilherme Lemeszenski (guilherme@nead.unesp.br) on 2013-08-22T18:48:30Z No. of bitstreams: 1 S0100-40422003000300017.pdf: 1235353 bytes, checksum: 513c5a0ee8b7bfde18670b97d46b04d2 (MD5) Made available in DSpace on 2013-08-22T18:48:30Z (GMT). No. of bitstreams: 1 S0100-40422003000300017.pdf: 1235353 bytes, checksum: 513c5a0ee8b7bfde18670b97d46b04d2 (MD5) Previous issue date: 2003-05-01 Made available in DSpace on 2013-09-30T19:38:27Z (GMT). No. of bitstreams: 2 S0100-40422003000300017.pdf: 1235353 bytes, checksum: 513c5a0ee8b7bfde18670b97d46b04d2 (MD5) S0100-40422003000300017.pdf.txt: 48210 bytes, checksum: 3e67fd5abbd61573874a7446f3c79476 (MD5) Previous issue date: 2003-05-01 Submitted by Vitor Silverio Rodrigues (vitorsrodrigues@reitoria.unesp.br) on 2014-05-20T15:10:19Z No. of bitstreams: 2 S0100-40422003000300017.pdf: 1235353 bytes, checksum: 513c5a0ee8b7bfde18670b97d46b04d2 (MD5) S0100-40422003000300017.pdf.txt: 48210 bytes, checksum: 3e67fd5abbd61573874a7446f3c79476 (MD5) Made available in DSpace on 2014-05-20T15:10:19Z (GMT). No. of bitstreams: 2 S0100-40422003000300017.pdf: 1235353 bytes, checksum: 513c5a0ee8b7bfde18670b97d46b04d2 (MD5) S0100-40422003000300017.pdf.txt: 48210 bytes, checksum: 3e67fd5abbd61573874a7446f3c79476 (MD5) Previous issue date: 2003-05-01 Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Many substances from different sources have been used by men for decades to control insects. After the 2nd World War, the use of inorganic compounds have declined drastically and natural products, as well as synthetic derivatives, have been widely used instead. The search for natural alternatives have improved the development of bench top bioassays and an array of synthetic approaches for known and novel natural products that shows relevant activities as feeding supressors and deterrents. The studies concerning mode of action and environmental impact of these substances, that may be biodegradable and selective for undesired insects, had led to the evaluation and discovery of a number of molecules, mostly terpenoids and alkaloids, that are well reported as candidates for inseticidal compounds that could be an effective alternative for insects control with a lower impact on human health, household animals and the environment. Universidade Estadual Paulista Júlio de Mesquita Filho Instituto de Química Universidade Estadual Paulista Júlio de Mesquita Filho Instituto de Química