DESENVOLVIMENTO ATRAVÉS DA SÍNTESE, ELUCIDAÇÃO ESTRUTURAL E AVALIAÇÃO BIOLÓGICA DE DERIVADOS 2-AMINO-TIOFÊNICOS-SUBSTITUÍDOS COMO POTENCIAIS FÁRMACOS ANTIFÚNGICOS

A resistência fúngica a agentes terapêuticos disponíveis no mercado tem aumentando significativamente, principalmente devido ao crescimento da população imunocomprometida e do uso indiscriminado de agentes Antifúngicos. O presente trabalho teve por objetivo realizar o desenvolvimento de entidades químicas sintéticas derivados do heterocíclico tiofeno associado a diferentes aldeídos substituídos diclorados, que possam ser utilizadas como potenciais agentes antifúngicos mais seguros, eficazes, potentes e menos tóxicos. O método utilizado para a obtenção dos núcleos partiu da reação de Gewald, já descrita na literatura, onde os núcleos são obtidos inicialmente depois condensados com aldeídos aromáticos em meio acido e etanólico. Os compostos tiveram suas estruturas comprovadas através de RMN1H e apresentaram rendimentos entre 55 e 83%. Os compostos serão avaliados frete a diferentes cepas fúgicas ATCC, e aqueles que se apresentarem mais ativos, serão avaliados frente a isolados clínicos

Cytotoxic and Schistosomidal Activities of Extract, Fractions and Isolated Compounds from Zanthoxylum Leprieurii (Rutaceae)

Schistosomiasis is a major and chronic neglected tropical disease. The existing treatment does not kill immature schistosomes and have serious adverse side effect.  It is well known that some parasites are responsible for causing specific cancers in humans including bladder cancer from Schistosoma haematobium infection. So, novel drugs discovery is an urgent need. In this study, were evaluated in vitro the cytotoxic on human hepatocarcinoma (HepG2) and normal cells (Chang liver), and the schistosomicidal properties of crude extract, fractions and isolated compounds (1-Hydroxy-3-methoxy-N-methylacridone (1) described in this species from Cameroon for the first time, Scoparone (2), and Arborinine (3)) from powdered fruits of Zanthoxylum leprieurii (Rutaceae). All fractions: hexanic (FH), methylene chloride (FC), ethyl acetate (FA) and methanolic (FM) killed all the cercariae within 2 hours exposure and presents LC50 values between 2 and 3 μg/ml; Compounds 1 and 3 also displayed a good in vitro schistosomicidal activity against cercariae with LC50 values of 78.78 and 6.98 μg/mL, respectively. For antitumor activity compounds 1-3 and fraction FC presents good activity with IC50 values range 18.27 - 74.61 μg/mL on HepG2 cells, however most of these were more toxic on Chang cells than to HepG2 cells, with only exception for compound 2. The acridone Arborinine (3) can constitute a good lead for the research of schistosomiasis alternative therapy, and the coumarin Scoparone (2) can be used in drug design as scaffold for design new potential anticancer agents

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear un derstanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5–7 vast areas of the tropics remain understudied.8–11 In the American tropics, Amazonia stands out as the world’s most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepre sented in biodiversity databases.13–15 To worsen this situation, human-induced modifications16,17 may elim inate pieces of the Amazon’s biodiversity puzzle before we can use them to understand how ecological com munities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple or ganism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region’s vulnerability to environmental change. 15%–18% of the most ne glected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lostinfo:eu-repo/semantics/publishedVersio

Pervasive gaps in Amazonian ecological research

Biodiversity loss is one of the main challenges of our time,1,2 and attempts to address it require a clear understanding of how ecological communities respond to environmental change across time and space.3,4 While the increasing availability of global databases on ecological communities has advanced our knowledge of biodiversity sensitivity to environmental changes,5,6,7 vast areas of the tropics remain understudied.8,9,10,11 In the American tropics, Amazonia stands out as the world's most diverse rainforest and the primary source of Neotropical biodiversity,12 but it remains among the least known forests in America and is often underrepresented in biodiversity databases.13,14,15 To worsen this situation, human-induced modifications16,17 may eliminate pieces of the Amazon's biodiversity puzzle before we can use them to understand how ecological communities are responding. To increase generalization and applicability of biodiversity knowledge,18,19 it is thus crucial to reduce biases in ecological research, particularly in regions projected to face the most pronounced environmental changes. We integrate ecological community metadata of 7,694 sampling sites for multiple organism groups in a machine learning model framework to map the research probability across the Brazilian Amazonia, while identifying the region's vulnerability to environmental change. 15%–18% of the most neglected areas in ecological research are expected to experience severe climate or land use changes by 2050. This means that unless we take immediate action, we will not be able to establish their current status, much less monitor how it is changing and what is being lost

Special Issue “Drug Discovery of Antiprotozoal Agents”

Protozoal diseases, such as leishmaniasis, malaria, African sleeping sickness, Chagas disease, amoebiasis, giardiasis, cryptococcosis, and toxoplasmosis (among others), affect and/or have the potential to infect more than one billion people worldwide [...

Síntese de Glicopiranosídeos 2,3 - insaturados acoplados a heterociclos em C-4. Funcionalização da posição C-5 de glicoheterociclos 4 (5 halo uracil l il) através de reações catalisadas por Pd (0)

Reações catalíticas promovidas por paládio(0) têm sido utilizadas nos últimos anos com sucesso para diversas reações de acoplamento entre carboidratos e bases nitrogenadas como nucleófilos para síntese de nucleosídeos e nucleotídeos com pronunciadas propriedades antivirais e anticancerígenas. Nos últimos 20 anos, paládio(0) também têm se mostrado versáteis ferramentas para a funcionalização de bases pirimidínicas de nucleosídeos, em especial através das reações de Heck, Suzuki, Stille e Sonogashira, resultando também em compostos biologicamente ativos. Essas reações, hoje, devidamente incorporadas aos procedimentos de síntese orgânica são amplamente utilizadas devido as alta regio- e estereosseletividade e amplo espectro de aplicações. O reação de acoplamento entre varios heterociclos e piranosídeos 2,3-insaturados mediado por Pd(0) como catalisador (reação de Tsuji-Trost) forneceu a formação de ligações C-N na posição alílica (C-4) da molécula do açúcar, gerando glicosídeos 2,3-insaturados acoplados a um núcelo heterocíclico nessa posição (105a-h). Os glicosídeos 105d (X = I) e 105e (X = Br) tiveram suas reatividades testados com uma variedade de compostos apresentando funções acetilênicas terminais, vinílicas e arila mediadas por Pd(0) como catalisador (reações de Heck, Stille, Suzuki e Sonogashira) com intuito de promover a funcionalização da posição C-5 do heterociclo uracila. Com esse intuito, a reação de Heck forneceu uma nova substância (106) em baixo rendimento (18%) com configuração E do grupo inserido. O acoplamento de Stille utilizando CuI como cocatalisador forneceu o composto desejado 108 em 86% de rendimento. Em contrapartida, o acoplamento de Suzuki forneceu três novos produtos (107a-c), em baixos rendimentos (∼5%). Acoplamento de Sonogashira produziu os glicoheterociclos (109a-l, 111) em rendimentos de bons a excelentes (41-98%). A reação de 105d com 1-hexino e dietino-1,4-benzeno gerou os esperados 109b e 111, e como produtos secundários 100 e 112, respectivamente. Os ensaios de atividade biológica desses novos compostos estão em andamento e deverão ter seus resultados apresentados brevemente

SAR, QSAR and Docking of Anticancer Flavonoids and Variants: A Review

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-04-04T13:34:32Z No. of bitstreams: 1 Scotti L SAR, QSAR and Docking of Anticancer Flavonoids....pdf: 545154 bytes, checksum: 71393247ab290fc268c1fd811528fcff (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-04-04T13:45:16Z (GMT) No. of bitstreams: 1 Scotti L SAR, QSAR and Docking of Anticancer Flavonoids....pdf: 545154 bytes, checksum: 71393247ab290fc268c1fd811528fcff (MD5)Made available in DSpace on 2018-04-04T13:45:16Z (GMT). No. of bitstreams: 1 Scotti L SAR, QSAR and Docking of Anticancer Flavonoids....pdf: 545154 bytes, checksum: 71393247ab290fc268c1fd811528fcff (MD5) Previous issue date: 2012CNPq, CAPES and FAPESQ. I. R. P. is thankful to the INCT_if; D.R.M.M. holds a FAPESBFederal University of Paraíba. Centre for Biotechnology. João Pessoa, PB, BrazilState University of Paraiba. Laboratory of Synthesis and Drug Delivery. Biological Science Department. João Pessoa, PB, BrazilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilFederal University of Paraíba. Centre for Biotechnology. João Pessoa, PB, BrazilFederal University of Pernambuco. Departamento de Antibióticos. Recife, PE, BrazilFederal University of Paraíba. Department of Engineering and the Environment. Rio Tinto, PB, BrazilFlavonoids are phenolic compounds, secondary metabolites of plants that cause several benefits to our health, including helping the treatment against cancer. These pharmacological properties are associated with the ability of flavonoids in attenuating the generation of reactive oxygen species, acting as chelate compounds or affecting the oxi-redox cycle. In spite of the large number of information in term of SAR and QSAR, no recent review has tabulated and discussed in detail these data. In view of this, we bring here a detailed discussion of the structure-activity relationships (SAR) and quantitative structure-activity relationships (QSAR) models. We have also analyzed the correlation between the chemical structure of flavonoids and analogues to their anticancer activities. A large number of methodologies have been used to identify the characteristics of these compounds with their potential anticancer: multiple linear regression, principal components analysis, comparative molecular field analysis, comparative molecular similarity indices analysis, partial least squares, neural networks, configuration of classification and regression trees, Free-Wilson, docking; using topological, structural and enthalpies’ descriptors. We also discussed the use of docking models, together with QSAR models, for the virtual screening of anticancer flavonoids. The importance of docking models to the medicinal chemistry of anticancer flavonoids has increased in the last decade, especially to help in identifying the structural determinants responsible for the activity. We tabulated here the most important examples of virtual screening determined for anticancer flavonoids and we highlighted the structural determinants. The mode of action, the most potent anticancer flavonoids and hints for the structural design of anticancer flavonoids are revised in details and provided here