Crystallography-based exploration of non-covalent interactions for the design and synthesis of coumarin for stronger protein binding.

Protein molecules are a good target for the inhibition or promotion of biological processes. Different methods like QSAR and molecular docking have been developed to accurately design small binder molecules for target proteins. An alternative model has been developed wherein a statistical method is used to find the propensity of different non-covalent interactions between small molecules and amino acid residues of the protein. The results give hints as to the choice of substituents required at the SM to strongly bind to a protein. In this case, 75 different types of proteins bound with coumarin derivatives have been investigated and the non-covalent interactions observed between the basic coumarin moiety and amino acids have been analyzed. Density functional theory (DFT) calculations were used to identify the electronic features of coumarin to understand the feasibility of the observed non-covalent interactions and to find appropriate groups that can modulate these interactions. The binding affinity towards a protein (ß-lactoglobulin (BLG)) and the stability of the protein complex have been investigated through docking and molecular dynamics of 100 ns, respectively. The modeled compounds were synthesized and investigated with regards to their interactions with the model carrier protein. The thermodynamics of the interactions were also investigated and the binding is governed by the Le Chatelier principle.

Surface modification minimizes the toxicity of silver nanoparticles: an in vitro and in vivo study.

Currently toxicological research in Silver nanoparticle is a leading issue in medical science. The surface chemistry and physical dimensions of silver nanoparticles (Ag-NPs) play an important role in toxicity. The aim of this present study was to evaluate the in vitro and in vivo toxicity of Ag-NPs as well as the alteration of toxicity profile due to surface functionalization (PEG and BSA) and the intracellular signaling pathways involved in nanoparticles mediated oxidative stress and apoptosis in vitro and in vivo system. Ag-NPs released excess Ag+ ions leads to activation of NADPH oxidase and helps in generating the reactive oxygen species (ROS). Silver nanoparticles elicit the production of excess amount of ROS results activation of TNF-α. Ag-NPs activates caspase-3 and 9 which are the signature of mitochondrial pathway. Ag-NPs are responsible to decrease the antioxidant enzymes and imbalance the oxidative status into the cells but functionalization with BSA and PEG helps to protect the adverse effect of Ag-NPs on the cells. This study suggested that Ag-NPs are toxic to normal cells which directly lead with human health. Surface functionalization may open the gateway for further use of Ag-NPs in different area such as antimicrobial and anticancer therapy, industrial use or in biomedical sciences.

Eugenol Provokes ROS-Mediated Membrane Damage-Associated Antibacterial Activity Against Clinically Isolated Multidrug-Resistant Staphylococcus aureus Strains.

Due to the indiscriminate use of antibiotics, resistance to antibiotics has increased remarkably in Staphylococcus aureus. Vancomycin is the final drug to treat the S. aureus infection, but nowadays, resistance to this antibiotic is also increasing. So, the investigation of antibiotic resistance pattern is important. As there is already resistance to vancomycin, there is an urgent need to develop a new kind of antimicrobial to treat S. aureus infection. Eugenol may be the new drug of choice. This study was conducted to evaluate the antibacterial activity of eugenol against vancomycin-resistant S. aureus isolated from clinical pus samples. Thirty six pus samples were included in the study. Samples were isolated, identified and antimicrobial susceptibility tests were performed as per routine laboratory protocol. The antimicrobial activity and mechanisms of killing of eugenol were studied. Out of 36 pus samples, only 20 isolates were confirmed as S. aureus strains and 6 isolates exhibited vancomycin resistance. Eugenol successfully destroyed the vancomycin-resistant strains via reactive oxygen species generation and membrane damage. The prevalence of vancomycin resistance is increased day by day in different countries, and necessary steps to prevent the spread and emergence of resistance should be taken. The findings of the study suggested that eugenol might be used to treat vancomycin-resistant S. aureus.

A novel tool for capture and detection of typhoid fever using Ag-labeled nanocomposites.

This work investigated a simple and versatile modification to a solid substrate to develop antibody recognition using nanoparticles. The new immobilized metal ion affinity adsorbent containing nanoparticles and hydrophilic resins is proposed here to improve the binding of antigen on its surface. The light-scattering properties of submicroscopic metal particles ranging from 100 to 120 nm in diameter were confirmed by scanning electron microscopy. We found that synthesized nanoparticles have an inherent enzyme mimetic activity similar to that found in natural peroxidases. The synthesized nanoparticles were coated with Salmonella typhi and Salmonella paratyphi antigens and were allowed to react with Salmonella-infected serum. Positive reactions were detected visually with the naked eye. The color changes of substrate (TMB) were observed even in 1:800 dilutions. This report helps in developing a specific immunoassay using nano-conjugated antigen for the rapid detection of S. typhi and S. paratyphi antibodies in infected serum.

Dereplication coupled with in vitro antioxidant assay of two flavonoid glycosides from Diospyros peregrina fruit.

Diospyros peregrina is an edible seasonal fruit found in coastal West Bengal, India. The fruits have been reported to possess a significant antioxidant activity. In this study, the aim was to isolate the lead compound responsible for the above-mentioned activity. The aqueous extract of D. peregrina fruit was subjected to dereplication coupled with an in vitro 1,1-diphenyl-2-picryl-hydrazyl (DPPH) radical scavenging assay. The n-butanol fraction of the aqueous extract of D. peregrina fruit exhibited significant antioxidant activity (IC(50), 131.10 µg mL(-1)) as compared with the parent extract (IC(50), 285.15 µg mL(-1)). The n-butanol fraction was subjected to silica gel column chromatographic separation coupled with a chemo-autographic study of column eluents, employing ethanolic DPPH as a spraying reagent. Two bioactive flavonoid glycosides, namely luteoline-4'-methyl-ether-7-O-glucoside and quercetin-3-O-(glucosyl)-glucoside, were identified to exhibit IC(50) values of 74.04 and 65.78 µg mL(-1), respectively in the DPPH assay.

Effect of bergapten from Heracleum nepalense root on production of proinflammatory cytokines.

In the present investigation, the anti-inflammatory activity of isolated bergapten from hydroalcoholic extract of Heracleum nepalense root was evaluated in vitro using human peripheral blood mononuclear cells (PBMCs). Bergapten exhibited significant inhibition of the production of pro-inflammatory cytokines, namely tumour necrotic factor-α (TNF-α) and interleukin-6 (IL-6) by PBMCs stimulated with lipopolysaccharide in a concentration-dependent manner.

Status of groundwater arsenic contamination in Bangladesh: a 14-year study report.

Since 1996, 52,202 water samples from hand tubewells were analyzed for arsenic (As) by flow injection hydride generation atomic absorption spectrometry (FI-HG-AAS) from all 64 districts of Bangladesh; 27.2% and 42.1% of the tubewells had As above 50 and 10 µg/l, respectively; 7.5% contained As above 300 µg/l, the concentration predicting overt arsenical skin lesions. The groundwater of 50 districts contained As above the Bangladesh standard for As in drinking water (50 µg/l), and 59 districts had As above the WHO guideline value (10 µg/l). Water analyses from the four principal geomorphological regions of Bangladesh showed that hand tubewells of the Tableland and Hill tract regions are primarily free from As contamination, while the Flood plain and Deltaic region, including the Coastal region, are highly As-contaminated. Arsenic concentration was usually observed to decrease with increasing tubewell depth; however, 16% of tubewells deeper than 100 m, which is often considered to be a safe depth, contained As above 50 µg/l. In tubewells deeper than 350 m, As >50 µg/l has not been found. The estimated number of tubewells in 50 As-affected districts was 4.3 million. Based on the analysis of 52,202 hand tubewell water samples during the last 14 years, we estimate that around 36 million and 22 million people could be drinking As-contaminated water above 10 and 50 µg/l, respectively. However for roughly the last 5 years due to mitigation efforts by the government, non-governmental organizations and international aid agencies, many individuals living in these contaminated areas have been drinking As-safe water. From 50 contaminated districts with tubewell As concentrations >50 µg/l, 52% of sampled hand tubewells contained As <10 µg/l, and these tubewells could be utilized immediately as a source of safe water in these affected regions provided regular monitoring for temporal variation in As concentration. Even in the As-affected Flood plain, sampled tubewells from 22 thanas in 4 districts were almost entirely As-safe. In Bangladesh and West Bengal, India the crisis is not having too little water to satisfy our needs, it is the challenge of managing available water resources. The development of community-specific safe water sources coupled with local participation and education are required to slow the current effects of widespread As poisoning and to prevent this disaster from continuing to plague individuals in the future.

Oxidative stress in the brain of nicotine-induced toxicity: protective role of Andrographis paniculata Nees and vitamin E.

Mitochondria are the crossroads of several crucial cellular activities; they produce considerable quantities of superoxide radical and hydrogen peroxide, which can damage important macromolecules. Nicotine affects a variety of cellular processes, from induction of gene expression to modulation of enzymatic activities. The aim of this study was to elucidate the protective effects of andrographolide (ANDRO) aqueous extract (AE-Ap) of Andrographis paniculata, and vitamin E on nicotine-induced brain mitochondria. In this investigation, nicotine (1 mg.kg body mass-1.day-1) was treated, for the period of 7 days, simultaneously with 2 A. paniculata products, ANDRO and AE-Ap (250 mg.kg body mass-1.day-1); and vitamin E (50 mg.kg body mass-1.day-1) was supplemented in different group of male Wistar rats. The activities of mitochondrial electron transport chain (Mito-ETC) complexes (I, II, III), nitric oxide production, superoxide anion, catalase, glutathione reductase, glutathione peroxidase, glutathione-S-transferase, and concentrations of reduced glutathione and oxidized glutathione were measured in discrete regions of brain (the cerebral hemisphere, cerebellum, diencephalons, and brain stem). The study revealed that nicotine inhibits the Mito-ETC complexes and produces nitric oxide, which suppressed the mitochondrial oxidative stress scavenger system in different brain regions. In these circumstances, lipid peroxidation and protein oxidation were noted in different discrete regions of brain mitochondria. ANDRO, AE-Ap, and vitamin E showed the protective potentiality against nicotine toxicity. The analysis of such alterations is important in determining the basis of normal dysfunction in the brain associated with nicotine toxicity, which could be ameliorated by A. paniculata and vitamin E, and may help to develop therapeutic means against nicotine-induced disorders.

Swietenine: a potential oral hypoglycemic from Swietenia macrophylla seed.

Swietenine, a tetranortriterpenoid, was isolated from the Swietenia macrophylla seeds. The in vivo hypoglycemic activity was evaluated against neonatal-streptozotocin induced type 2 diabetic rats. Oral administration of swietenine at 25 and 50 mg/kg body weight per day to diabetic rats was found to possess significant dose dependant hypoglycemic and hypolipidemic activity in type 2 diabetic rats.

Alpha-tocopherol supplementation on chromium toxicity: a study on rat liver and kidney cell membrane.

Membrane damage is one of the important consequence of chromium, an environmental toxicant, to produce cytotoxicity, alpha-tocopherol, a membrane protectant can be used to reduce the chromium-induced membrane damage. In the present study, the impact of chromium in presence and absence of alpha-tocopherol was studied on plasma membrane of liver and kidney in male Wistar rats (80-100 g body weight). Significant increase in membrane cholesterol level as well as significant decrease in membrane phospholipid level in chromium exposed (0.8 mg/100 g body weight/d, i.p., for 4 weeks) animals suggest structural alteration of both liver and kidney plasma membrane. The alkaline phosphatase, total ATPase and Na(+)-K(+)-ATPase activities of plasma membrane were significantly decreased in both liver and kidney after chromium treatment. However, alpha-tocopherol (30 mg/100 g diet) supplementation can restrict the changes in these membrane-bound enzyme activities. Thus, the usefulness of dietary supplementation of alpha-tocopherol to restrain the chromium-induced membrane damage is suggested.

6-(2-Hydroxybenzoyl)-5-(pyrrol-2-yl)-3H-pyrrolizine.

The title compound, 2-hydroxyphenyl 5-(pyrrol-2-yl)-3H-pyrrolizin-6-yl ketone, C(18)H(14)N(2)O(2), was isolated from the base-catalyzed 1:2 condensation of 2-hydroxyacetophenone with pyrrole-2-carbaldehyde. The pyrrole N-H and hydroxybenzoyl O-H groups are hydrogen bonded to the benzoyl O atom. The allylic C=C double bond of the 3H-pyrrolizine system is located between ring positions 1 and 2, the C atom at position 3 (adjacent to the N atom) being single bonded.

Effect of chromium on certain aspects of metabolic toxicities.

The impact of chromium exposure was studied in the liver, kidney, testis, spleen, cerebrum, and cerebellum of male Wistar rats (80-100 g body weight). It was observed that treatment of rats with chromium (ip, at a dose of 0.8 mg/100 g body weight/day) for a period of 28 days caused significant increase in chromium content while lowering the body weight along with the organ weight, except for the liver. It was also observed that there was a significant decrease in the DNA content of various organs tested. Also, a significant decrease in RNA content was observed in all the organs tested except for the testes. The liver, cerebrum, and cerebellum showed significant decreases in total protein content in chromium-treated animals, whereas the kidney, testes, and spleen showed insignificant alterations. The RNase activity was found to be significantly increased only in the testes and cerebrum. Pronase activity was significantly increased in the tissues, except for the liver. The glutamic-pyruvic acid transaminase activity decreased in all the tissues studied. On the other hand, glutamic-oxaloacetic acid transaminase activity increased in the liver, cerebrum, and cerebellum while decreasing in the kidney and spleen. It is suggested that chromium exposure at the present dose and duration induces metabolic toxicity in the form of depressive effects on nucleic acids and altered activities of RNase, pronase, and transaminases in tissues. The extent of such alterations varies from tissue to tissue and is in some cases diverse in nature.