Development of Computational Approaches with a Fragment-Based Drug Design Strategy: In Silico Hsp90 Inhibitors Discovery.

A semi-exhaustive approach and a heuristic search algorithm use a fragment-based drug design (FBDD) strategy for designing new inhibitors in an in silico process. A deconstruction reconstruction process uses a set of known Hsp90 ligands for generating new ones. The deconstruction process consists of cutting off a known ligand in fragments. The reconstruction process consists of coupling fragments to develop a new set of ligands. For evaluating the approaches, we compare the binding energy of the new ligands with the known ligands.

Update on drug transporter proteins in acute myeloid leukemia: Pathological implication and clinical setting.

Acute myeloid leukemia (AML) is one of the most common hematological neoplasia causing death worldwide. The long-term overall survival is unsatisfactory due to many factors including older age, genetic heterogeneity and molecular characteristics comprising additional mutations, and resistance to chemotherapeutic drugs. The expression of ABCB1/P-glycoprotein, ABCC1/MRP1, ABCG2/BCRP and LRP transporter proteins is considered the major reason for multidrug resistance (MDR) in AML, however conflicting data have been reported. Here, we review the main issues about drug transporter proteins in AML clinical scenario, and highlight the clinicopathological significance of MDR phenotype associated with ABCB1 polymorphisms and FLT3 mutation.

Recent Advances in the Development of "Curcumin Inspired" Compounds as New Therapeutic Agents.

Despite a huge body of research in the past two decades investigating the antioxidant, antiinflammatory, anti-microbial, and anti-carcinogenic properties of curcumin (CUR), a CUR-based antitumor drug is yet to be developed. Lack of success in achieving this goal stems from CUR's unfavorable biophysicochemical features, particularly poor solubility, low bioavailability, and rapid metabolism, coupled with a complex biological profile making it difficult to determine its mechanism of action. A significant body of literature aimed at improving its physicochemical properties through synthesis or by designing delivery methods has been published, and the progress in these areas has been reviewed. The present review aims to summarize recent progress in the synthesis of structurally diverse "curcumin-inspired" compounds along with computational docking and bioassay studies, through which a number of promising analogs have been identified that warrant further study.

Exploring the chemical space of peptides for drug discovery: a focus on linear and cyclic penta-peptides.

Peptide and peptide-like structures are regaining attention in drug discovery. Previous studies suggest that bioactive peptides have diverse structures and may have physicochemical properties attractive to become hit and lead compounds. However, chemoinformatic studies that characterize such diversity are limited. Herein, we report the physicochemical property profile and chemical space of four synthetic linear and cyclic combinatorial peptide libraries. As a case study, the analysis was focused on penta-peptides. The chemical space of the peptide and N-methylated peptides libraries was compared to compound data sets of pharmaceutical relevance. Results indicated that there is a major overlap in the chemical space of N-methylated cyclic peptides with inhibitors of protein-protein interactions and macrocyclic natural products available for screening. Also, there is an overlap between the chemical space of the synthetic peptides with peptides approved for clinical use (or in clinical trials), and to other approved drugs that are outside the traditional chemical space. Results further support that synthetic penta-peptides are suitable compounds to be used in drug discovery projects.

Baixa digestibilidade proteica e presença de antinutricionais em produtos tipo mix de cereais / Low protein digestibility and anti-nutritional factors in cereal mix like products

Products composed of cereal mixes and other ingredients such as guarana, gelatin and cocoa powders; yeast; and soybean, flaxseed and sesame extracts have presented increased sales while receiving ever-growing criticism. Amongst the ingredients that could compose this cereal mix, most are of vegetable origin, wholegrain and not thermally processed. Therefore, they may present anti-nutritional factors, which are recognized to harm the bioavailability of nutrients, such as proteins. In this study, we aimed to evaluate the protein quality of these products, sold in the municipality of Uberaba, Brazil. The protein digestibility, tannins and trypsin inhibitors of the 14 samples were assessed. All samples showed trypsin inhibition activity and tannins. These results suggest that those products present low potential for nutrient utilization, especially with regards to proteins.

Productos compuestos por mezclas de cereales y otros ingredientes, como guaraná en polvo, gelatina en polvo, cacao en polvo, levadura de cerveza, extracto de soja, linaza y ajonjolí, presentan creciente comercialización, al mismo tiempo que aumentan los cuestionamientos al respecto. Estos productos están compuestos de variados ingredientes, la mayoría de origen vegetal, integral y sin procesamiento térmico previo, y podrían presentar antinutricionales, reconocidamente capaces de perjudicar la biodisponibilidad de nutrientes, tales como las proteínas. Este estudio evaluó la calidad proteica de productos listos para el consumo, compuestos por mezclas de cereales y otros componentes, comercializados en la ciudad de Uberaba-MG, determinando sus niveles antinutricionales y su digestibilidad proteica in vitro. Todas las muestras analizadas presentaron inhibición en la actividad de tripsina y de taninos. Las muestras presentaron muy claramente bajos valores de digestibilidad proteica in vitro. Los resultados sugieren que estos productos presentan bajo potencial de utilización de sus nutrientes, muy especialmente con respecto a sus proteínas.

Misturas de cereais e outros ingredientes, como guaraná em pó, gelatina em pó, cacau em pó, levedo de cerveja, extrato de soja, linhaça e gergelim, vêm apresentando crescente comercialização, concomitantemente com crescentes questionamentos a seu respeito. Dentre os ingredientes variados que podem compor estes produtos, a maioria é de origem vegetal, integral e sem processamento térmico prévio, e poderiam apresentar antinutricionais, reconhecidamente capazes de prejudicar a biodisponibilidade de nutrientes, como proteínas. Este trabalho buscou avaliar a qualidade proteica de produtos prontos para o consumo, compostos por misturas de cereais e outros componentes, comercializados no município de Uberaba-MG, determinando seus teores de antinutricionais e sua digestibilidade proteica in vitro. Todas as amostras analisadas apresentaram atividade de inibição de tripsina e teores de taninos, e baixa digestibilidade in vitro.