An approach to zwitterionic peptide design for colorimetric detection of the Southampton norovirus SV3CP protease.

Noroviruses are highly contagious and are one of the leading causes of acute gastroenteritis worldwide. Due to a lack of effective antiviral therapies, there is a need to diagnose and surveil norovirus infections to implement quarantine protocols and prevent large outbreaks. Currently, the gold standard of diagnosis uses reverse transcription polymerase chain reaction (RT-PCR), but PCR can have limited availability. Here, we propose a combination of a tunable peptide substrate and gold nanoparticles (AuNPs) to colorimetrically detect the Southampton norovirus 3C-like protease (SV3CP), a key protease in viral replication. Careful design of the substrate employs a zwitterionic peptide with opposite charged moieties on the C- and N- termini to induce a rapid color change visible to the naked eye; thus, this color change is indicative of SV3CP activity. This work expands on existing zwitterionic peptide strategies for protease detection by systematically evaluating the effects of lysine and arginine on nanoparticle charge screening. We also determine a limit of detection for SV3CP of 28.0 nM with comparable results in external breath condensate, urine, and fecal matter for 100 nM of SV3CP. The key advantage of this system is its simplicity and accessibility, thus making it an attractive tool for qualitative point-of-care diagnostics

Correlação entre o transporte manual de material e lombalgia em trabalhadores / Correlation between manual transport of material and lombalgia in workers

Os equipamentos para o transporte de material vêm sendo cada vez mais utilizados, no entanto, o transporte manual de materiais (TMM) ainda é bastante usado e mostra ser eficaz. Essas tarefas exercidas diariamente com carga e movimentos de torção e flexão, podem gerar uma compressão da coluna vertebral desencadeando um fator de risco para lombalgia. Esta pesquisa é de natureza transversal, do tipo observacional, com abordagem quantitativa e propósito exploratório. Onde os critérios de inclusão foram empresas que trabalham com o transporte de ração animal, que contenham no mínimo três funcionários, sendo do sexo masculino, maiores de 18 anos e que exercem a função por pelo menos quatro vezes na semana. Foram incluídos na pesquisa 22 participantes e aplicado o Questionário Nórdico de Sintomas Osteomusculares (QNSO), voltado para avaliar a prevalência da lombalgia. Nos últimos sete dias, apenas 18% da amostra, sentiram dor lombar. Entretanto, nos últimos 12 meses 59% dos participantes foram acometidos. O estudo mostrou que quem sentiu dor lombar nos últimos sete dias, tem idade média 38,25±16,8, tempo de trabalho e IMC elevados comparado a quem não sentiu dor. Nos últimos 12 meses, os trabalhadores que apresentaram lombalgia, tem o tempo de trabalho e o IMC elevados, apresentando menor idade média 32,3±4,7. O presente estudo pode contribuir para a realização de estudos futuros, e assim traçar um perfil epidemiológico nessa população

2-Pyridyl thiazoles as novel anti-Trypanosoma cruzi agents: structural design, synthesis and pharmacological evaluation

The present work reports on the synthesis, anti-Trypanosoma cruzi activities and docking studies of a novel series of 2-(pyridin-2-yl)-1,3- thiazoles derived from 2-pyridine thiosemicarbazone. The majority of these compounds are potent cruzain inhibitors and showed excellent inhibition on the trypomastigote form of the parasite, and the resulting structure-activity relationships are discussed. Together, these data present a novel series of thiazolyl hydrazones with potential effects against Chagas disease and they could be important leads in continuing development against Chagas disease

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Antitumor and immunomodulatory activities of thiosemicarbazones and 1,3-Thiazoles in Jurkat and HT-29 cells

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2016-12-29T13:13:53Z No. of bitstreams: 1 Santos TAR Antitumor and immunomodulatory....pdf: 770132 bytes, checksum: b6d055670f9e6f1821da4d2895ab7c0d (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2016-12-29T13:24:03Z (GMT) No. of bitstreams: 1 Santos TAR Antitumor and immunomodulatory....pdf: 770132 bytes, checksum: b6d055670f9e6f1821da4d2895ab7c0d (MD5)Made available in DSpace on 2016-12-29T13:24:03Z (GMT). No. of bitstreams: 1 Santos TAR Antitumor and immunomodulatory....pdf: 770132 bytes, checksum: b6d055670f9e6f1821da4d2895ab7c0d (MD5) Previous issue date: 2016Brazilian National Research Council (CNPq), Research Foundation of Pernambuco State (FACEPE) and FIOCRUZ.Fundação Oswaldo Cruz. Centro de Pesquisa Aggeu Magalhães. Laboratório de Imunogenética. Recife, PE, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Aggeu Magalhães. Laboratório de Imunogenética. Recife, PE, BrasilUniversidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Recife, PE, BrasilUniversidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Recife, PE, BrasilUniversidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Recife, PE, BrasilUniversidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Recife, PE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilUniversidade Federal de Pernambuco. Departamento de Ciências Farmacêuticas. Recife, PE, BrasilFundação Oswaldo Cruz. Centro de Pesquisa Aggeu Magalhães. Laboratório de Imunogenética. Recife, PE, BrasilCancer remains a high incidence and mortality disease, causing around 8.2 million of deaths in the last year. Current chemotherapy needs to be expanded, making research for new drugs a necessary task. Immune system modulation is an emerging concept in cancer cell proliferation control. In fact, there are a number of mechanisms underlying the role immune system plays in tumor cells. In this work, we describe the structural design, synthesis, antitumor and immunomodulatory potential of 31 new 1,3-thiazole and thiosemicarbazone compounds. Cisplatin was used as anticancer drug control. Cytotoxicity against J774A.1 macrophages and antitumor activity against HT-29 and Jurkat cells was determined. These 1,3-thiazole and thiosemicarbazone compounds not only exhibited cytotoxicity in cancer cells, but were able to cause irreversible cancer cell damage by inducing necrosis and apoptosis. In addition, these compounds, especially pyridyl-thiazoles compounds, regulated immune factors such as interleukin 10 and tumor necrosis factor, possible by directing immune system in favor of modulating cancer cell proliferation. By examining their pharmacological activity, we were able to identify new potent and selective anticancer compounds

Small molecule in situ resin capture provides a compound first approach to natural product discovery

Culture-based microbial natural product discovery strategies fail to realize the extraordinary biosynthetic potential detected across earth's microbiomes. Here we introduce Small Molecule In situ Resin Capture (SMIRC), a culture-independent method to obtain natural products directly from the environments in which they are produced. We use SMIRC to capture numerous compounds including two new carbon skeletons that were characterized using NMR and contain structural features that are, to the best of our knowledge, unprecedented among natural products. Applications across diverse marine habitats reveal biome-specific metabolomic signatures and levels of chemical diversity in concordance with sequence-based predictions. Expanded deployments, in situ cultivation, and metagenomics facilitate compound discovery, enhance yields, and link compounds to candidate producing organisms, although microbial community complexity creates challenges for the later. This compound-first approach to natural product discovery provides access to poorly explored chemical space and has implications for drug discovery and the detection of chemically mediated biotic interactions

Desing and synthesis of potent anti-Trypanosoma cruzi agents new thiazoles derivatives which induce apoptotic parasite death

Submitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-04-04T17:27:48Z No. of bitstreams: 1 Silva EB Desing and synthesis of potent....pdf: 1101357 bytes, checksum: 05dda8ac2e41eb232464eae9599dab02 (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-04-04T17:42:18Z (GMT) No. of bitstreams: 1 Silva EB Desing and synthesis of potent....pdf: 1101357 bytes, checksum: 05dda8ac2e41eb232464eae9599dab02 (MD5)Made available in DSpace on 2018-04-04T17:42:18Z (GMT). No. of bitstreams: 1 Silva EB Desing and synthesis of potent....pdf: 1101357 bytes, checksum: 05dda8ac2e41eb232464eae9599dab02 (MD5) Previous issue date: 2017Conselho Nacional de Desenvolvimento Científico e Tecnol ogico, Fundaç~ao de Amparo a Ci^encia e Tecnologia de Pernambuco (FACEPE).Universidade Federal de Pernambuco. Centro de Ciências da Saúde. Departamento de Ciências Farmacêuticas. Recife, PE, Brasil / Universidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, BrasilUniversidade Federal de Pernambuco. Centro de Ciências da Saúde. Departamento de Ciências Farmacêuticas. Recife, PE, BrasilUniversidade Federal de Pernambuco. Centro de Ciências da Saúde. Departamento de Ciências Farmacêuticas. Recife, PE, BrasilUniversidade Federal de Pernambuco. Centro de Ciências da Saúde. Departamento de Ciências Farmacêuticas. Recife, PE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, Brasil / Universidade Federal de Pernambuco. Centro Acadêmico de Vit oria. Laborat orio de Parasitologia. Vit oria de Santo Antão, PE, BrasilUniversidade Federal de Minas Gerais. Departamento de Bioquímica e Imunologia. Belo Horizonte, MG, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Gonçalo Moniz. Salvador, BA, BrasilUniversidade de Pernambuco. Colegiado de Nutrição. Petrolina, PE, BrasilUniversidade de São Paulo. Instituto de Física. Departamento de Física e Inform atica. São Carlos, SP, BrasilFundação Oswaldo Cruz. Centro de Pesquisas Aggeu Magalhães. Recife, PE, BrasilUniversidade Federal de Pernambuco. Centro de Ciências da Saúde. Departamento de Ciências Farmacêuticas. Recife, PE, BrasilChagas disease, caused by the kinetoplastid protozoan parasite Trypanosoma cruzi, remains a relevant cause of illness and premature death and it is estimated that 6 million to 7 million people are infected worldwide. Although chemotherapy options are limited presenting serious problems, such as low efficacy and high toxicity. T. cruzi is susceptible to thiazoles, making this class of compounds appealing for drug development. Previously, thiazoles resulted in an increase in anti-T. cruzi activity in comparison to thiosemicarbazones. Here, we report the structural planning, synthesis and anti-T. cruzi evaluation of new thiazoles derivatives (3a-m and 4a-m), designed from molecular hybridization associated with non-classical bioisosterism. By varying substituents attached to the phenyl and thiazole rings, substituents were observed to retain, enhance or greatly increase their anti-T. cruzi activity, in comparison to the corresponding thiosemicarbazones. In most cases, electron-withdrawing substituents, such as bromine, 3,4-dichloro and nitro groups, greatly increased antiparasitic activity. Specifically, new thiazoles were identified that inhibit the epimastigote proliferation and were toxic for trypomastigotes without affecting macrophages viability. These compounds were also evaluated against cruzain. However, inhibition of this enzyme was not observed, suggesting that the compounds work through another mechanism. In addition, examination of T. cruzi cell death showed that these molecules induce apoptosis. In conclusion, except for compounds 3h and 3k, all thiazoles derivatives evaluated exhibited higher cytotoxic activity against the trypomastigote forms than the reference medicament benznidazole, without affecting macrophages viability. Compounds 4d and 4k were highlights, CC50 = 1.2 e 1.6 μM, respectively. Mechanistically, these compounds do not inhibit the cruzain, but induce T. cruzi cell death by an apoptotic process, being considered a good starting point for the development of new anti-Chagas drug candidates

Phthaloyl amino acids as anti-inflammatory and immunomodulatory prototypes

Moreira, Diogo Rodrigo de Magalhães. Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Brasil. “Documento produzido em parceria ou por autor vinculado à Fiocruz, mas não consta à informação no documento”. A. C. L. Leite (&) F. F. Barbosa M. V. O. Cardoso D. R. M. Moreira L. C. D. Coêlho E. B. da Silva G. B. O. Filho V. M. O. de Souza Departamento de Ciências Farmacêuticas, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, Recife, PE 50740-520, Brazil e-mail: [email protected] V. R. A. Pereira L. de C. Reis Departamento de Imunologia, Centro de Pesquisas Ageu Magalhães-FIOCRUZ, Recife, PE, Brazil P. M. P. Ferreira Departamento de Ciências Biológicas, Universidade Federal do Piauí, Picos, Piauí 64607-670, Brazil C. Pessoa Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal do Ceará, Fortaleza, CE 60430-270, Brazil A. G. Wanderley Departamento de Fisiologia e Farmacologia, Centro de Ciências da Saúde, Universidade Federal de Pernambuco, Recife, PE 50740-520, Brazil F. V. B. Mota T. G. da Silva Departamento de Antibio´ticos, Universidade Federal de Pernambuco, Recife, PE 50740-520, BrazilSubmitted by Ana Maria Fiscina Sampaio ([email protected]) on 2018-06-13T16:17:18Z No. of bitstreams: 1 Leite ACL Phthaloyl amino....pdf: 345295 bytes, checksum: 14d3393083d9e023a78131372f340ade (MD5)Approved for entry into archive by Ana Maria Fiscina Sampaio ([email protected]) on 2018-06-13T16:30:02Z (GMT) No. of bitstreams: 1 Leite ACL Phthaloyl amino....pdf: 345295 bytes, checksum: 14d3393083d9e023a78131372f340ade (MD5)Made available in DSpace on 2018-06-13T16:30:02Z (GMT). No. of bitstreams: 1 Leite ACL Phthaloyl amino....pdf: 345295 bytes, checksum: 14d3393083d9e023a78131372f340ade (MD5) Previous issue date: 2014Brazilian National Research Council (CNPq), FACEPE, and FIOCRUZMúltipla – ver em NotasAbstract A series of phthalimide analogs were synthesized by derivatization of phthalic anhydride, a highly toxic substance, using a ‘‘one pot’’ condensation reaction to a-amino acids. All phthaloyl amino acid derivatives presented anti-oral inflammatory activity, but compounds 2e and 2g were found to possess the best activities comparable to thalidomide.Most of the compounds effectively suppressed nitric oxide production inmurine cells stimulatedwith lipopolysaccharide.Nphthaloyl amino acids did not exhibit any significant cytotoxicity in vitro when tested against tumor cells as well as a spleen cell culture of BALB/c mice. Compounds 2a, 2g, and 2h were able to inhibit TNF-a and IL-1b production by macrophages. At the same concentration, thalidomide did not exhibit significant inhibitory activity