A series of 2-amino-1,4-naphthoquinone derivatives (NQA-NQF) was synthesized by alternative methods (ultrasonication and microwave irradiation), with yields ranging from 40 to 71%, and without the need of further recrystallization. Each compound was evaluated against four Gram-positive (Bacillus subtilis, Enterococcus faecalis, Staphylococcus aureus and Bacillus cereus) and five Gram-negative (Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, Acinetobacter baumannii and Klebsiella pneumoniae positive β-lactamase) bacteria strains. The NQF was the most active amino-naphthoquinone derivative with minimum inhibitory concentration (MIC) of 31.2 µg mL-1 against K. pneumoniae positive β-lactamase (a common intestinal bacteria which can cause life-threatening infections). On the other hand, NQA and NQC showed good activity as a potential antibiotic for the bacteria strains assayed, except for K. pneumoniae. In addition, the affinity of these three most active compounds (NQA, NQC, and NQF) for human serum albumin (HSA) was evaluated employing multiple spectroscopic techniques (steady-state, time-resolved, and synchronous fluorescence, as well as circular dichroism), combined with theoretical calculations (molecular docking). The interaction HSA:2-amino-1,4-naphthoquinones occurs spontaneously and moderately inside the subdomain IIA (Sudlow’s site I) via hydrogen bonding and van der Waals forces.

A series of α-acetyloxy-N-cyclohexylamides was efficiently obtained via Passerini reaction of cyclohexyl isocyanide, acetic acid, and different aromatic and aliphatic aldehydes using refluxing dichloromethane or dimethylcarbonate (DMC). Reactions performed with DMC led to desired products in moderate to good yields, corroborating this solvent as a eco-friendly alternative to the chlorinated solvents commonly used in this transformation. The α-acetyloxy-N-cyclohexylamides thus obtained were tested against Escherichia coli, Bacillus cereus, Pseudomonas aeruginosa, and Staphylococcus aureus, as well as promastigote forms of L.(L.) amazonensis. The α-(Acetyloxy)-N-cyclohexyl-pentanamide showed low antibacterial activity against Gram-positive (S. aureus and B. cereus) and Gram negative (E. coli and P. aeruginosa) bacteria (MIC = 8,3-16,5 mmol L-1), while α-(acetyloxy)-N-cyclohexyl-4-bromo-benzeneacetamide showed leishmanicidal activitity (IC50 = 0,099 mmol L-1).

OBJETIVO: Avaliar o comportamento de biomarcadores de formação e reabsorção óssea em adolescentes brasileiros em função da sua maturação biológica. MÉTODOS: Oitenta e sete voluntários foram divididos em grupos segundo a idade óssea (IO): 10-12 anos (n = 25), 13-15 anos (n = 36) e 16-18 anos (n = 26). Foram analisados peso (kg), estatura (m), índice de massa corporal (kg/m2), ingestão de cálcio de 3 dias (mg/dia), avaliação dos eventos pubertários pelos critérios de Tanner, níveis dos biomarcadores [osteocalcina (OC) (ng/mL), fosfatase alcalina óssea (FAO) (U/L), telopeptídeo carboxiterminal sérico (S-CTx) (ng/mL)] e sua correlação com a densidade mineral óssea (DMO) (g/cm2) por atenuação de raios X de dupla energia da coluna lombar, do fêmur proximal e de corpo total. RESULTADOS: Os biomarcadores mostraram comportamento semelhante, apresentando medianas elevadas dos 13 aos 15 anos (FAO = 154,71 U/L, OC = 43,0 ng/mL, S-CTx = 2,09 ng/mL; p < 0,01) e no estágio puberal G4. As medianas decresceram com o avançar da IO e da maturação sexual. Os níveis dos biomarcadores mostraram paralelismo com pico de velocidade em estatura, e, curiosamente, os biomarcadores de formação indicaram correlação negativa com a DMO, isto é, valores de DMO elevados se correlacionaram com valores baixos dos biomarcadores. CONCLUSÕES: Este é o primeiro estudo em adolescentes brasileiros com critérios de inclusão e exclusão rígidos e cuidadosos a avaliar a correlação entre marcadores ósseos e DMO frente a indicadores da maturação biológica. Os resultados ajudam a compreender o turnover ósseo e o monitoramento do metabolismo ósseo.

OBJECTIVE: To evaluate the behavior of biomarkers of bone formation and resorption in healthy male Brazilian adolescents according to their biological maturation. METHODS: Eighty-seven volunteers were divided into age groups according to bone age (BA): 10-12 years (n = 25), 13-15 years (n = 36), and 16-18 years (n = 26). Weight (kg), height (m), body mass index (kg/m2), calcium intake from 3 days assessed by 24-h food recall (mg/day), pubertal event evaluation by Tanner criteria, and serum biomarker levels (osteocalcin [OC] [ng/mL], bone alkaline phosphatase [BAP] [U/L], and serum carboxyterminal telopeptide [S-CTx] [ng/mL]) were recorded and correlated to bone mineral density (BMD) (g/cm2) measured by dual energy X-ray absorptiometry of the lumbar spine, proximal femur, and whole body. RESULTS: Biomarkers showed similar behaviors, presenting higher median values in the 13-15 year group (BAP = 154.71 U/L, OC = 43.0 ng/mL, S-CTx = 2.09 ng/mL; p < 0.01) and when adolescents were in the pubertal stage G4. Median biomarker values decreased with advancing BA and sexual maturation. Biomarker values showed parallelism with peak height velocity, and, interestingly, bone formation biomarkers indicated significant negative correlation with BMD in the different evaluated locations, i.e., higher BMD values correlated with lower bone biomarker values. CONCLUSIONS: This is the first study of healthy Brazilian adolescents with rigid and careful inclusion and exclusion criteria to assess the correlation of bone markers and BMD with biological maturation indicators. Our results can help understand bone turnover and monitor bone metabolism.

Mating-type genes control the entry into the sexual cycle, mating identity and sexual development in fungi. The mat A-2 and mat A-3 genes, present in the mat A idiomorph of the filamentous fungus Neurospora crassa, are required for post-fertilization functions but are not essential for mating identity. Their putative roles as transcription factors are based on the similarity of mat A-2 with the Podospora anserina SMR1 gene and an HMG motif present in the mat A-3 gene. In this work the yeast two-hybrid system was used to identify transcriptional activity and protein-protein interaction of N. crassa mat A-2 and mat A-3 genes. We observed that the mat A-3 protein alone is capable of weakly activating transcription of yeast reporter genes; it also binds with low specificity to the GAL1 promoter sequence, possibly due to its HMG domain. Our results also indicate that mat A-3 is capable to form homodimers, and interact with mat A-2. Interference on yeast growth was observed on some transformants suggesting a toxic action of the mat A-2 protein. Our data on pattern of interactions of mat proteins contributes towards understanding the control of vegetative and sexual cycles in filamentous fungi.

Mineralización ósea en adolescentes brasileños: años de máxima incorporación de masa ósea. La pubertad es un momento fundamental para la adquisición de la masa ósea (MO). En este período, la mineralización se encuentra en aumento en los niveles de formación ósea. Los años críticos de intenso anabolismo óseo necesitan de atención, porque el adecuado aumento de la masa ósea podría minimizar el riesgo de fracturas en los años posteriores. El objetivo de esta investigación fue estudiar el contenido mineral óseo (CMO) y la densidad mineral ósea (DMO) en adolescentes según el grupo de edad y el nível de maduración. Sesenta y un adolescentes saludables de 10 a 19 años fueron evaluados cuanto a la ingesta de calcio, peso, estatura, índice de masa corpórea (IMC), etapa puberal, CMO y DMO en la columna lumbar y en el fémur. La MO fue medida por densitometría ósea (DEXA). La ingesta de calcio fue calculada mediante un recordatorio de ingesta de tres días. La etapa puberal fue definida por los criterios de Tanner. Estadística descriptiva fue utilizada con media y desviación estándar, correlación linear y análisis de varianza para comparar los grupos y test de Tukey (p<0,05). Correlación linear fue positiva e indicó que el peso corporal fue la principal variable correlacionada con la DMO en los dos sitios estudiados (p<0,01). CMO y DMO aumentaron con la edad y las diferencias fueron considerables de los 14 a los 15 años, cuando los adolescentes alcanzaban la etapa G4 de Tanner. Estos resultados muestran un aumento pronunciado en la mineralización ósea; entre los 14 y 15 años fueron críticos para la adquisición de MO en adolescentes brasileños

Puberty is the fundamental period for bone mass (BM) acquisition. In this period mineralization is found to increase with levels of high bone formation. The critical years of intense bone anabolism deserve special attention, as adequate gain could minimize fracture risk in later years. The objective of this work was to study bone mineral content (BMC) and bone mineral density (BMD) in male adolescents with age bracket and maturation level. Sixty-one healthy male 10 to 19 year-olds were evaluated for calcium intake, weight, stature, BMI, puberty stage and BMC and BMD in the lumbar spine and femur. BM was measured by bone densitometry (DXA). Calcium intake was calculated by recording 3 days diet. Puberty stage was defined as per Tanner. Descriptive statistics was used with means and standard deviations, linear correlation, and analysis of variance for comparison between age groups, and the Tukey test (p<0.05). Linear correlation was positive and indicated body weight as the main correlation variable with BMD in both studied locations (p<0.01). BMC and BMD increased with age, differences were significant from 14 to 15 years, and when adolescents reached Tanner stage G4. These results showed a pronounced increase in bone mineralization, with the years after 14 to 15 being critical for BM acquisition in Brazilian adolescents

Considerada um grave problema de saúde pública, estudos indicam que a osteoporose é uma doença pediátrica com manifestações clínicas apresentadas na senilidade. O diagnóstico de osteopenia/ osteoporose é normalmente feito na prática clínica através da densitometria óssea por atenuação de raio-x de dupla energia (DXA). O exame é de alto custo e de difícil aplicação em populações pediátricas em virtude do emprego de aparelhagem específica e software especial. O presente estudo propõe equações preditivas para avaliação da densidade mineral óssea (DMO) em adolescentes do sexo masculino. Foram recrutados 61 adolescentes saudáveis na faixa de 10 a 19 anos e obtidos a idade óssea (através do raio-x de mão e punho esquerdo), maturação sexual, o peso, a estatura, a DMO na coluna lombar e no fêmur proximal total. A estruturação dos modelos de predição foi realizada pela análise de regressão múltipla "stepwise". Os resultados indicaram modelos de predição para DMO com coeficientes de correlação de 0,87 para região da coluna e 0,80 para região femoral. Esses resultados confirmam que a DMO depende da idade esquelética e do crescimento físico durante a adolescência. As equações propostas são de fácil aplicação, baixo custo operacional e com poder explicativo superior a 75% e 65%, respectivamente para a DMO da coluna lombar e fêmur proximal total.

Osteoporosis is considered one of the most serious public health diseases and studies show that it is a pediatric disease that manifests during senility. It is usually diagnosed in clinical practice by dual-energy x-ray absorptiometry (DXA). This exam has a high cost and it is difficult to apply to a pediatric population because specific equipment and special software are required. This study presents predictive equations to evaluate the bone mineral density (BMD) among male adolescents. To better predict the equations, some parameters were used as the bone age (by left hand and wrist x-ray), pubertal stages, weight, height and the lumbar spine and femur BMD from 61 healthy adolescents, ages 10 through 19 years. The prediction models were carried through analysis of multiple regressions stepwise. The results have indicated a prediction model for BMD with a coefficient of 0.87 and 0.80, respectively for the spine and the femoral regions. In conclusion, the results have confirmed that BMD depends on the skeletal age and the physical growth during adolescence. The proposed equations are easy to use, has a low operational cost, and the clarification rate is 75% and 65% for lumbar spine and femoral BMD, respectively.

OBJETIVO: Verificar o comportamento do conteúdo mineral ósseo e da densidade mineral óssea em adolescentes do sexo masculino em função da faixa etária e do nível maturacional dos caracteres sexuais secundários. MÉTODOS: 47 adolescentes saudáveis na faixa etária de 10 a 19 anos foram avaliados quanto a ingestão de cálcio, peso, estatura, índice de massa corporal, estágio puberal, densidade mineral óssea e conteúdo mineral ósseo na coluna e no fêmur proximal. A massa óssea foi mensurada através de densitometria óssea. A ingestão de cálcio foi calculada através de registro dietético de 3 dias. O índice de massa corporal foi calculado pelo Índice de Quetelet, e o estágio puberal foi definido segundo os critérios de Tanner. Foi utilizada estatística descritiva, média e desvio padrão, análise de variância para comparação entre os grupos etários e teste de Tukey para localizar as diferenças significativas. RESULTADOS: A ingestão de cálcio não alcançou o valor mínimo de 800 mg em várias faixas etárias estudadas. A densidade mineral óssea e o conteúdo mineral ósseo demonstraram incrementos com o avançar da idade, indicando diferenças significativas a partir dos 14 anos, bem como quando os adolescentes atingiam os estágios de maturação sexual G4. Os parâmetros de mineralização revelaram aumento pronunciado quando os adolescentes atingiam G3, porém sem significado estatístico. CONCLUSÃO: Os resultados apontam um aumento importante na mineralização óssea durante a adolescência. A evidência de aumento na mineralização dos adolescentes foi percebida em níveis maturacionais superiores a G3. Os anos críticos para a aquisição da massa óssea neste estudo evidenciaram-se a partir dos 14-15 anos de idade.

OBJECTIVE: To verify the behavior of the mineral bone content and density in male adolescents according to age and secondary sexual characters. METHODS: 47 healthy adolescents between 10 and 19 years old were assessed according to weight, height, body mass index, puberty stage, calcium intake, bone mineral density and content in the lumbar spine and in the proximal femur. The bone mass was measured through bone densitometries. The intake of calcium was calculated through a 3-day diet. The BMI (body mass index) was calculated with the Quetelet Index and the puberty stage was defined according to Tanner's criteria. The analysis used descriptive statistics such as average and standard deviation, and variance estimates to compare the different age groups. Moreover, the Tukey test was used to determine the significant differences. RESULTS: It was evident that the calcium intake in the different ages assessed has not reached the minimum value of 800 mg. The bone mineral density and content showed an increase after the age of 14, as well as when the teenagers reached the sexual maturation stage G4. The mineralization parameters showed a high level when the teenagers were in the G3 stage, however, without statistical significance. CONCLUSION: The results indicate an important level of bone mineralization during adolescence. Maturation levels superior to G3 have shown more mineralization. This study proves that the critical years for bone mass gain start after the 14-15 years old or older.