Benzimidazol-1-yl-1-phenylpropanone Analogs as Potent Antimicrobial Agents: Rational Design and Synthesis

Designed, synthesized a sequence of novel benzimidazol-1-yl-1-phenylpropanone hybrids and assessed for in vitro antimicrobial potential counter to several bacterial strains. Computational Methodology was carried out for designing of the target molecules and structures were confirmed by spectroscopic analysis. Amid the 12 integrated derivatives, (3-(2-((3-fluorobenzylidene)amino)-1H-benzo[d]imidazol-1-yl)-1-phenylpropan-1-one ( 6g ) and 3-(2-((4-fluorobenzylidene)amino)-1H-benzo[d]imidazol-1-yl)-1-phenylpropan-1-one ( 6k ) were found to acquire excellent antibacterial activity against all bacterial strains (Escherichia coli, Pseudomonas aeruginosa, Bacillus subtilis, Staphylococcus aureus), whereas derivative 3-(2-((2-fluorobenzylidene)amino)-1H-benzo[d]imidazol-1-yl)-1-phenylpropan-1-one ( 6c ), was potent against Escherichia coli, Bacillus subtilis, Staphylococcus aureus and displayed moderate action against P. aeruginosa. Derivatives with NO₂ substituent at 3^rd and 4^th position, 3-(2-((3-nitroobenzylidene)amino)-1H-benzo[d]imidazol-1-yl)-1-phenylpropan-1-one ( 6h ) and 3-(2-((4-nitroobenzylidene)amino)-1H-benzo[d]imidazol-1-yl)-1-phenylpropan-1-one ( 6 l ) respectively declared good to moderate results against all bacterial strains. Further, 3-(2-((3-chlorobenzylidene)amino)-1H-benzo[d]imidazol-1-yl)-1-phenylpropan-1-one ( 6f ) and 3-(2-((4-chlorobenzylidene)amino)-1H-benzo[d]imidazol-1-yl)-1-phenylpropan-1-one ( 6j ) were found to be more competent against both fungal strains (C. albicans, A. niger). Serial two-fold dilution method was used for the entire study and standard drugs utilized were ciprofloxacin and clotrimazole. MIC values (μg/ml) of novel synthesized analogs were reported in comparison to standard drugs for antibacterial and antifungal actions. Molecular docking studies showed that designed molecules dynamically bound with effective area of the receptor (DNA gyrase B, Clotrimazole complex of cytochrome P 45046A1) and in vitro results were in accord with in silico studies.     

Modulation of antioxidant enzymes,SIRT1 and NF‐κB by resveratrol and nicotinamide in alcohol‐aflatoxin B1‐induced hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is the fifth most commonly diagnosed cancer worldwide and is associated with poor prognosis. The current study aimed to assess the therapeutic efficacy of resveratrol when administered alone and in combination with nicotinamide against alcohol‐aflatoxin B1‐induced HCC. Results reveal that during the development and progression of cancer, there was a decline in the level of antioxidant enzymes catalase, glutathione peroxidase, glutathione reductase (GR), antioxidant glutathione, and glutathione S‐transferase, which is an enzyme of detoxification pathways. Treatment of resveratrol restored the level of catalase and glutathione peroxidase toward normal in alcohol‐aflatoxin B1‐induced HCC; however, nicotinamide worked in concert with resveratrol only in upregulating the activity of glutathione reductase, glutathione level, and glutathione S‐transferase. SIRT1 agonist resveratrol was observed to modulate the activity of antioxidant enzymes by negatively regulating the expression of nuclear factor‐κB (NF‐κB) in alcohol‐aflatoxin B1‐induced HCC, thereby suggesting a cross‐talk between antioxidant enzymes SIRT1 and NF‐κB during the development and progression of HCC and its therapeutics by resveratrol and nicotinamide.     

Trace Elements Contents in <Emphasis Type=Italic>Asparagus curillus</Emphasis> (Buch.-Ham.) ex Roxb.

Concentration level of nine elements viz. Zn, Cu, Mn, Fe, Co, Na, K, Ca, and Li were determined in leaves and roots of Asparagus curillus (Buch.-Ham.) ex Roxb. collected from four different altitudes in three seasons by atomic absorption spectroscopy. The overall concentration of K was found to be highest, whereas the level of Cu was lowest. The maximum concentrations of Zn, Cu, Mn, Fe, Co, Na, K, Ca, and Li were found to be 97.0 ± 1.5, 28.0 ± 7.0, 44.0 ± 7.3, 1138.0 ± 18.5, 91.0 ± 6.2, 381.0 ± 7.8, 9508.0 ± 7.8, 3076.0 ± 6.4, and 78.0 ± 4.6 mg/kg, respectively.     

Body Fat Patterning,Hepatic Fat and Pancreatic Volume of Non-Obese Asian Indians with Type 2 Diabetes in North India: A Case-Control Study

ObjectiveTo evaluate body fat patterning and phenotype including hepatic fat and pancreatic volume of non-obese (BMI: < 25 kg/m²) Asian Indians with type 2 diabetes residing in North India.MethodsNon-obese patients with type 2 diabetes (n = 93) and non-obese, normo-glycemic subjects (n = 40) were recruited. BMI, waist & hip circumferences, skinfold thickness at 8 sites, body fat, lean mass and detailed abdominal fat evaluation [total abdominal fat, total subcutaneous fat (superficial, deep, anterior, and posterior), total intra-abdominal fat (intra-peritoneal, retroperitoneal)], liver span, grades of fatty liver and pancreatic volume were compared.ResultsWaist circumference, subscapular skinfolds and total truncal fat (on DEXA) were higher whereas calf, total peripheral skinfolds and total leg fat (on DEXA) lower in patients. Specifically, the following volumes were higher in cases as compared to controls; total abdominal fat (19.4%), total intra-abdominal fat (49.7%), intra-peritoneal fat (47.7%), retroperitoneal fat (70.7%), pancreatic volume (26.6%), pancreatic volume index (21.3%) and liver span (10.8%). In cases, significant positive correlations were observed for pancreatic volume with BMI, waist and hip circumferences, W-HR, subscapular, abdominal and total truncal skinfolds, truncal, total subcutaneous, total intra-abdominal, intra-peritoneal, retroperitoneal fat depots, liver span and fatty liver.ConclusionsIn non-obese Asian Indians with type 2 diabetes, subcutaneous and intra-abdominal obesity, including fatty liver, and pancreatic volume were higher and peripheral subcutaneous adiposity was lower than BMI matched non-diabetic subjects. Importantly, increased pancreatic volume in patients was highly correlated with multiple measures of abdominal obesity and liver fat.     

Ontology-Based Meta-Analysis of Global Collections of High-Throughput Public Data

Background

The investigation of the interconnections between the molecular and genetic events that govern biological systems is essential if we are to understand the development of disease and design effective novel treatments. Microarray and next-generation sequencing technologies have the potential to provide this information. However, taking full advantage of these approaches requires that biological connections be made across large quantities of highly heterogeneous genomic datasets. Leveraging the increasingly huge quantities of genomic data in the public domain is fast becoming one of the key challenges in the research community today.

Methodology/Results

We have developed a novel data mining framework that enables researchers to use this growing collection of public high-throughput data to investigate any set of genes or proteins. The connectivity between molecular states across thousands of heterogeneous datasets from microarrays and other genomic platforms is determined through a combination of rank-based enrichment statistics, meta-analyses, and biomedical ontologies. We address data quality concerns through dataset replication and meta-analysis and ensure that the majority of the findings are derived using multiple lines of evidence. As an example of our strategy and the utility of this framework, we apply our data mining approach to explore the biology of brown fat within the context of the thousands of publicly available gene expression datasets.

Conclusions

Our work presents a practical strategy for organizing, mining, and correlating global collections of large-scale genomic data to explore normal and disease biology. Using a hypothesis-free approach, we demonstrate how a data-driven analysis across very large collections of genomic data can reveal novel discoveries and evidence to support existing hypothesis.     

Antidyslipidemic activity of polyprenol from Coccinia grandis in high-fat diet-fed hamster model

Ethanol extract of Coccinia grandis (L.) Voigt showed significant triglyceride (TG) and cholesterol-lowering effects in dyslipidemic hamster model. Ethanolic extract was fractionated into chloroform, n-butanol and water-soluble fractions and were evaluated. Activity was proved to be concentrated in chloroform-soluble fraction. Chloroform-soluble fraction containing active component was subjected to repeated column chromatography, furnished a polyprenol characterized as C₆₀-polyprenol (1) isolated for the first time from this plant. It significantly decreased serum TG by 42%, total cholesterol (TC) 25% and glycerol (Gly) 12%, accompanied HDL-C/TC ratio 26% in high-fat diet (HFD)-fed dyslipidemic hamsters at the dose of 50 mg/kg body weight. Results are comparable to standard drug fenofibrate at the dose of 108 mg/kg. Based on these investigations, it was concluded that the compound polyprenol (1) isolated from leaves of C. grandis possess marked antidyslipidemic activity.     

The glycosyltransferase gene encoding the enzyme catalyzing the first step of mycothiol biosynthesis (mshA)

Mycothiol is the major thiol present in most actinomycetes and is produced from the pseudodisaccharide 1D-myo-inosityl 2-acetamido-2-deoxy-alpha-D-glucopyranoside (GlcNAc-Ins). A transposon mutant of Mycobacterium smegmatis shown to be GlcNAc-Ins and mycothiol deficient was sequenced to identify a putative glycosyltransferase gene designated mshA. The ortholog in Mycobacterium tuberculosis, Rv0486, was used to complement the mutant phenotype.