UTILIZAÇÃO DE FERRAMENTAS IN SILICO PARA A IDENTIFICAÇÃO DE INIBIDORES DA TIROSINA FOSFATASE A DO Mycobacterium tuberculosis

A tuberculose (TB) é uma doença infectocontagiosa causada pela Mycobacterium tuberculosis que afeta principalmente os pulmões, mas, também pode ocorrer em outros órgãos do corpo (tuberculose extrapulmonar). Mesmo sendo uma das doenças infecciosas mais antigas, bem conhecida e há mais de meio século vulnerável ao tratamento medicamentoso, a TB permanece como um dos principais agravos à saúde a ser enfrentado em âmbito global (GENGENBACHER et al., 2008)

Effect of probiotics on the intestinal microbiota of preterm and low birth weight infants: systematic review

Premature infants have an immature intestinal microbiota when compared to a full-term baby, colonized with a reduced number of beneficial bacterial species and, therefore, are more likely to have their microbiota populated by pathogenic species. The administration of probiotics can positively influence the intestinal colonization of premature babies. Thus, this study aimed to systematically review evidences of the effect of administering probiotics on the microbiota of premature newborns and their safety. It was designed as follows: population (premature newborns), intervention (probiotics), comparison (placebo or no treatment), outcome (changes in the microbiota of premature newborns), study type (randomized clinical trials). The studies were searched in the Cochrane Library, Medline via PubMed and Embase databases and, in a complementary way, through manual searches on Google Scholar and the Brazilian CAPES journal portal (www.periodicos.capes.gov.br). We included 23 studies involving 3,670 preterm infants, of which 65.2% (n=15) were classified as having a low risk of bias, 17.4% (n=4) with some risk of bias and 17.4% (n= 4) with high risk of bias. Probiotics have been used in order to colonize the intestinal microbiota. Finally, some Lactobacillus and Bifidobacterium strains tested seem to have benefits and safety for the microbiota and health of premature newborns

Ocotea daphnifolia: phytochemical investigation, in vitro dual cholinesterase inhibition, and molecular docking studies

This study aimed to evaluate the anticholinesterase activities of extracts and fractions of Ocotea daphnifolia in vitro and characterize its constituents. The effects of hexane, ethyl acetate, and ethanolic extracts on acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) activity were determined with a spectrophotometry assay. All extracts inhibited cholinesterase activity, and the ethanolic extract (2 mg/mL) exhibited the highest inhibition of both enzymes (99.7% for BuChE and 82.4% for AChE). The ethanolic extract was fractionated by column chromatography resulting in 14 fractions that were also screened for their anticholinesterase effects. Fraction 9 (2 mg/mL) showed the highest activity, inhibiting AChE and BuChE by 71.8% and 90.2%, respectively. This fraction was analyzed by high-performance liquid chromatography high-resolution mass spectrometry which allowed the characterization of seven glycosylated flavonoids (containing kaempferol and quercetin nucleus) and one alkaloid (reticuline). In order to better understand the enzyme-inhibitor interaction of the reticuline toward cholinesterase, molecular modeling studies were performed. Reticuline targeted the catalytic activity site of the enzymes. Ocotea daphnifolia exhibits a dual cholinesterase inhibitory activity and displays the same pattern of intermolecular interactions as described in the literature. The alkaloid reticuline can be considered as an important bioactive constituent of this plant

Pharmacological treatment for osteoporosis

The increase of life expectancy has led several concerns about people's quality of life, especially in the health area. In this context, there is an increase in the incidence of chronic degenerative diseases, as such as osteoporosis. This research aims to conduct a theoretical study about the pharmacological and non-pharmacological therapies available for the preventation and treatment of this disease. This study becomes important as it intends to show the main pharmacological and non-pharmacological drugs used in the treatment and mainly in the prevention of this disease, so prevalent nowadays. The methodology used for this study was a literature review and it aimed to compile the main available information about the theme of the study. Osteoporosis is a bone metabolic disease, characterized by a decrease in bone mass and deterioration of the microarchitecture of bone tissue, resulting in a raise of fracture susceptibility, and it is mainly related to age, affecting men and women. The therapeutic agents used in the treatment of osteoporosis can be divided into two classes: compounds with an anti-reabsorptive action (bisphosphonates, calcitonin, estrogens and selective estrogen receptor modulators) and bone-forming agents (fluoride, parathyroid hormone, teriparatide). Some newer drugs, as strontium ranelate, are also available for the use in the treatment of this disease.</p

8-Methoxypsoralen is a competitive inhibitor of glutathioneS-transferase P1-1

The blood-brain barrier (BBB) is known to protect healthy brain cells from potentially dangerous chemical agents, but there are many evidences supporting the idea that this protective action is extended to tumor cells. Since the process of angiogenesis in brain tumors leads to BBB breakdown, biochemical characteristics of the BBB seem to be more relevant than physical barriers to protect tumor cells from chemotherapy. In fact, a number of resistance related factors were already demonstrated to be component of both BBB and tumor cells. The enzyme glutathione S-transferases (GST) detoxify electrophilic xenobiotics and endogenous secondary metabolites formed during oxidative stress. A role has been attributed to GST in the resistance of cancer cells to chemotherapeutic agents. This study characterized 8-methoxypsoralen (8-MOP) as a human GST P1-1 (hGST P1-1) inhibitor. To identify and characterize the potential inhibitory activity of 8-MOP, we studied the enzyme kinetics of the conjugation of 1-chloro-2,4-dinitrobenzene (CDNB) with GSH catalyzed by hGST P1-1. We report here that 8-MOP competitively inhibited hGST P1-1 relative to CDNB, but there was an uncompetitive inhibition relative to GSH. Chromatographic analyses suggest that 8-MOP is not a substrate. Molecular docking simulations suggest that 8-MOP binds to the active site, but its position prevents the GSH conjugation. Thus, we conclude that 8-MOP is a promising prototype for new GST inhibitors pharmacologically useful in the treatment of neurodegenerative disorders and the resistance of cancer to chemotherapy.CNPq/BN

8-Methoxypsoralen is a competitive inhibitor of glutathioneS-transferase P1-1

The blood-brain barrier (BBB) is known to protect healthy brain cells from potentially dangerous chemical agents, but there are many evidences supporting the idea that this protective action is extended to tumor cells. Since the process of angiogenesis in brain tumors leads to BBB breakdown, biochemical characteristics of the BBB seem to be more relevant than physical barriers to protect tumor cells from chemotherapy. In fact, a number of resistance related factors were already demonstrated to be component of both BBB and tumor cells. The enzyme glutathione S-transferases (GST) detoxify electrophilic xenobiotics and endogenous secondary metabolites formed during oxidative stress. A role has been attributed to GST in the resistance of cancer cells to chemotherapeutic agents. This study characterized 8-methoxypsoralen (8-MOP) as a human GST P1-1 (hGST P1-1) inhibitor. To identify and characterize the potential inhibitory activity of 8-MOP, we studied the enzyme kinetics of the conjugation of 1-chloro-2,4-dinitrobenzene (CDNB) with GSH catalyzed by hGST P1-1. We report here that 8-MOP competitively inhibited hGST P1-1 relative to CDNB, but there was an uncompetitive inhibition relative to GSH. Chromatographic analyses suggest that 8-MOP is not a substrate. Molecular docking simulations suggest that 8-MOP binds to the active site, but its position prevents the GSH conjugation. Thus, we conclude that 8-MOP is a promising prototype for new GST inhibitors pharmacologically useful in the treatment of neurodegenerative disorders and the resistance of cancer to chemotherapy