This study aimed to isolate, purify and characterize secondary metabolites present in Amburana acreana leaves, native to the state of Rondônia, using classical chromatographic methods and 1D, 2D nuclear magnetic resonance spectroscopy. From the hydroethanolic leaves extract of A. acreana, p-hydroxybenzoic acid, vanillic acid, coumarin, campesterol 3-β-D-glucoside and amburoside B, all known compounds, were identified. To the best of our knowledge, this is the first report of isolation and chemical characterization of secondary metabolites in A. acreana. In addition, in vitro assays indicated that amburoside B does not have inhibitory potential on the growth of gram-negative bacteria. The presence of these compounds suggests that, thus far, amburosides (A and B) could be chemotaxonomic markers of the genus Amburana. isolate Rondônia 1D D spectroscopy A phydroxybenzoic p hydroxybenzoic acid coumarin 3βDglucoside βDglucoside 3 β glucoside identified knowledge addition gramnegative gram negative bacteria far

Durante as últimas décadas as infecções fúngicas têm se tornado um crescente problema de saúde, especialmente para pacientes imunocomprometidos. Infelizmente, o padrão-ouro de terapia profilática para tal doença é baseada em derivados azólicos, que são mais fungistáticos do que fungicidas contra C. neoformans e causam hepatotoxicidade. Objetivando contornar estes problemas, inibidores não-azólicos de CYP51 foram planejados. Aqui, um abrangente estudo de relação estrutura-atividade foi executado para uma série de 110 moléculas através de um estudo de QSAR baseado em hologramas e descritores moleculares. O melhor modelo de QSAR baseado em descritores (r² = 0,92, q² = 0,90, 6 LVs e r²pred =0,86) sugere que o efeito de ressonância (ESpm08r) desempenha um papel principal para a atividade antifúngica. O modelo de QSAR baseado em hologramas (r² = 0,87, q² = 0,81, 6 LVs e r²pred = 0,84) sustenta esta hipótese. Estas percepções obtidas pelas análises integradas dos modelos de QSAR, juntamente com o bom poder preditivo comprovam sua utilidade para futuros esforços em planejamento de fármacos.

Over the last decades fungal infections have become an increasing health problem, especially for immunocompromised patients. Unfortunately, the gold standard prophylactic therapy for such ailment is based on azole derivatives, which are fungistatic rather than fungicidal against C. neoformans and cause hepatotoxicity. Aiming at circumvent these problems, non-azole CYP51 inhibitors were designed. Herein a comprehensive structure-activity relationships study was carried out for a dataset of 110 molecules by means of hologram- and descriptor-based QSAR studies. The best descriptor-based QSAR model (r² = 0.92, q² = 0.90, 6 LVs and r²pred =0.86) suggests that resonance effects (ESpm08r) play a major role for antifungal activity. The hologram-based QSAR (r² = 0.87, q² = 0.81, 6 LVs and r²pred = 0.84) supports this hypothesis and hints at steric properties that should also contribute to non-azole inhibitors potency. The insights provided by the integrated analysis of QSAR models, along with their good predictive power prove their usefulness to future drug design efforts.

Apesar dos avanços no desenvolvimento de antifúngicos, tem ocorrido um aumento de casos de criptococose que não respondem de forma adequada a fluconazol (fármaco de primeira escolha). Portanto, é de suma importância investigar as propriedades químicas de derivados azólicos que sejam ativos contra cepas de Cryptococcus neoformans resistentes a fluconazol. Visando alcançar esse objetivo, o perfil de suscetibilidade de um isolado clínico de C. neoformans resistente contra 33 derivados azólicos comerciais foi avaliado junto com as suas respectivas concentrações inibitórias mínimas (MIC). Esses dados foram utilizados para construir modelos SIMCA (modelagem independente flexível por analogias de classes) que destacam a importância de propriedades eletrônicas (JGI10) para separar as moléculas ativas das inativas e para construir modelos de holograma-QSAR que apresentam bom ajuste, mas capacidade preditiva baixa (HQSAR, r² = 0.85, q² = 0.35 e r²pred = 0.38). Por outro lado, modelos de QSAR 2D desenvolvidos a partir de descritores topológicos apresentaramm boa qualidade estatística (r² = 0.95, q² = 0.86, r²pred = 0.72) e destacam que a distribuição de cargas (GGI1) e a eletronegatividade topológica (GATS1e e MATS2e) devem ser modulados para contornar a resistência de C. neoformans.

Despite advances in the development of antifungal drugs, there has been an upsurge of cryptococosis infections that poorly respond to fluconazole (first choice drug). Hence, it is paramount to investigate the chemical properties of azole derivatives that are active against resistant C. neoformans. In order to achieve this goal, the susceptibility profile of a clinical isolate of resistant C. neoformans against 33 commercial azole derivatives was evaluated along with their potency (minimum inhibitory concentration, MIC). These data were employed to build SIMCA (soft independent modeling of class analogies) models that pinpoint the importance of electronic features (JGI10) to separate active from inactive compounds and hologram-QSAR models that have good fit but insufficient predictive power (HQSAR, r² = 0.85, q² = 0.35 and r²pred = 0.38). Conversely, 2D QSAR models built from topological descriptors improved the statistical quality (r² = 0.95, q² = 0.86, r²pred = 0.72) and highlight that charge distribution (GGI1) and topological electronegativity (GATS1e and MATS2e) should be modulated to overcome the C. neoformans resistance.

Em pacientes com insuficiência coronariana aguda e choque cardiogênico, a mortalidade é alta. O dispositivo mais utilizado para suporte hemodinâmico é o balão intra-aórtico que, no entanto, pode ser insuficiente em pacientes com choque cardiogênico refratário. Relato de caso com dois dias de dor precordial opressiva e intensa, irradiada para membro superior esquerdo. ECG com supradesnivelamento anterior. Realizado angioplastia e implante de stent na artéria descendente anterior. Evolução com choque cardiogênico refratário ao uso de drogas vasoativas e balão intra-aórtico. Foram realizadas medidas hemodinâmicas e decidiu-se pela colocação do Impella® 2,5 por via percutânea para assistência circulatória.

Mortality is high in patients with acute coronary failure and cardiogenic shock. The most commonly used device for hemodynamic support is the intra-aortic balloon, which, however, may be insufficient in patients with refractory cardiogenic shock. This is a case report of a patient complaining of two days of intense and oppressive chest pain, radiating to the left arm. The ECG showed ST elevation. The patient was submitted to angioplasty and stent implant in the anterior descending artery and developed cardiogenic shock refractory to vasoactive drugs and intra-aortic balloon. Hemodynamic measures were carried out and we chose to use an Impella 2.5 device, by percutaneous route, for circulatory support.

Azole derivatives are the main therapeutical resource against Candida albicans infection in immunocompromised patients. Nevertheless, the widespread use of azoles has led to reduced effectiveness and selection of resistant strains. In order to guide the development of novel antifungal drugs, 2D-QSAR models based on topological descriptors or molecular fragments were developed for a dataset of 74 molecules. The optimal fragment-based model (r² = 0.88, q² = 0.73 and r²pred = 0.62 with 6PCs) and descriptor-based model (r² = 0.82, q² = 0.79 and r²pred = 0.70 with 2 PCs), when analysed synergically, suggested that the triazolone ring and lipophilic properties are both important to antifungal activity.

A enzima purina nucleosídeo fosforilase de Schistosoma mansoni (SmPNP) é um alvo molecular atrativo para o tratamento de importantes doenças infecciosas parasitárias, com especial ênfase para o seu papel na descoberta de novos fármacos contra a esquistossomose, uma doença tropical que afeta cerca de 200 milhões de pessoas em 74 áreas endêmicas no mundo todo. No presente trabalho, a potência inibitória foi determinada e estudos das relações quantitativas entre a estrutura e atividade (QSAR), baseados em descritores e fragmentos, foram desenvolvidos para uma série de 9-deazaguaninas que atuam como inibidores da SmPNP. Parâmetros estatísticos significantes (modelo baseado em descritor: r² = 0,79; q² = 0,62, r²pred = 0,52; e modelo baseado em fragmento: r² = 0,95; q² = 0,81; r²pred = 0,80) foram obtidos, indicando o potencial dos modelos para compostos ainda não testados. O modelo baseado em fragmento foi então usado para predizer a potência inibitória de um conjunto teste de compostos, e os valores preditos estão em boa concordância com os resultados experimentais.

The enzyme purine nucleoside phosphorylase from Schistosoma mansoni (SmPNP) is an attractive molecular target for the treatment of major parasitic infectious diseases, with special emphasis on its role in the discovery of new drugs against schistosomiasis, a tropical disease that affects millions of people worldwide. In the present work, we have determined the inhibitory potency and developed descriptor- and fragment-based quantitative structure-activity relationships (QSAR) for a series of 9-deazaguanine analogs as inhibitors of SmPNP. Significant statistical parameters (descriptor-based model: r² = 0.79, q² = 0.62, r²pred = 0.52; and fragment-based model: r² = 0.95, q² = 0.81, r²pred = 0.80) were obtained, indicating the potential of the models for untested compounds. The fragment-based model was then used to predict the inhibitory potency of a test set of compounds, and the predicted values are in good agreement with the experimental results

Paciente de 35 anos de idade foi atendido em Serviço de Emergência com seis horas de dor em fossa ilíaca direita e febre. Feita hipótese diagnóstica de apendicite aguda e realizada laparotomia exploradora. com apendicectomia. O paciente retornou ao hospital três dias após alta hospitalar. prostrado. febril. com alteração de fala. diminuição de nível de consciência e com hemiparesia completa à esquerda. CT scan de crânio e punção de líquor normal. RMN de encéfalo revelou aspectos compatíveis com AVC isquêmico vertebro-basilar. Ecocardiograma transesofágico demonstrou vegetação em valva aórtica e insuficiência aórtica moderada e hemoculturas foram positivas para Enterococcus bovis.

A 35-year-old patient was seen in an Emergency Department. with six hours of pain in the right iliac fossa and fever. The hypothesis diagnosis was acute appendicitis and an exploring laparotomy for appendectomy was carried out. The patient returned to the hospital three days after having been discharged. debilitated. feverish. having alterations in speech. reduction in the level of consciousness and complete hemiparesis to the left. The computed tomography scan of the skull and the liquor puncture were normal. Cerebral magnetic resonance image showed aspects compatible with vertebrobasilar ischemic stroke. Transesphofagic echocardiogram showed vegetation of the aortic valve and moderate aortic insufficiency. Blood cultures were positive for Enterococcus bovis.

Paciente de 35 años de edad ingresó en el servicio de emergencia con seis horas de dolor en fosa ilíaca derecha y fiebre. Se llevó a cabo la hipótesis diagnóstica de apendicitis aguda y realizada laparotomía exploradora, con apendicectomía. El paciente regresó al hospital tres días tras alta hospitalaria, prostrado, febril, con alteración de habla, disminución de nivel de conciencia y con hemiparesia izquierda completa. Scanner de cráneo y punción de líquido cefalorraquídeo (LCR) normal. RMN de encéfalo reveló aspectos compatibles con ACV isquémico vertebrobasilar. El ecocardiograma transesofágico demostró vegetación en válvula aórtica y insuficiencia aórtica moderada y hemocultivos fueron positivas para Enterococcus bovis.

Alzheimer's disease (AD) is considered the main cause of cognitive decline in adults. The available therapies for AD treatment seek to maintain the activity of cholinergic system through the inhibition of the enzyme acetylcholinesterase. However, butyrylcholinesterase (BuChE) can be considered an alternative target for AD treatment. Aiming at developing new BuChE inhibitors, robust QSAR 3D models with high predictive power were developed. The best model presents a good fit (r²=0.82, q²=0.76, with two PCs) and high predictive power (r²predict=0.88). Analysis of regression vector shows that steric properties have considerable importance to the inhibition of the BuChE.