Porous nanocomposites for sorptive elimination of ibuprofen from synthetic wastewater and its molecular docking studies.

Pharmaceuticals are a new developing pollutant that is threatening aquatic ecosystems and impacting numerous species in the ecosystem. The aim of this study is the green synthesis of TiO2-Fe2O3-Chitosan nanocomposites in conjunction with Moringa olifera leaves extract and its applicability for ibuprofen removal. Various characterization studies were performed for the synthesized nanocomposites. Box-Behnken design (BBD) is employed to optimize pH, agitation speed, and composite dosage. Equilibrium results show that adsorption process matches with Langmuir isotherm, demonstrating adsorption on the nanocomposite's homogenous surface and follows pseudo-first-order kinetics. Using the BBD, pH, adsorbent dose, and agitation speed were examined as adsorption parameters. Ibuprofen elimination was demonstrated to be most successful at a pH of 7.3, using 0.05 g of nanocomposites at a rotational speed of 200 rpm. Thermodynamic parameters for ibuprofen sorption were carried out and the ΔH and ΔS was found to be 76.23 & 0.233. Molecular Docking was performed to find the interaction between the pollutant and the nanocomposite. UV-vis spectra confirm the 243 nm absorption band corresponding to the nanocomposite's surface plasmon resonances. Fourier transform infrared spectroscopy spectra relate this band to a group of nanocomposites. The findings of this work emphasize the importance of TiO2-Fe2O3-Chitosan nanocomposites for removing ibuprofen from wastewater.

Green synthesis of bio-functionalized nano-particles for the application of copper removal - characterization and modeling studies.

Green technology for the synthesis of nanoparticles has gained momentum due to its cost-effectiveness and eco-friendly nature. In this research study, silver nanoparticles (AgNps) were synthesized using an eco-friendly biological method involving the use of marine algae, Halimeda gracilis. The surface properties of the synthesized silver nanoparticles were studied using UV-visible spectroscopy, Fourier transform infrared spectroscopy and scanning electron microscopy methods. During the synthesis of nano particles, the parameters namely temperature (30 °C to 90 °C), pH (6-10), silver nitrate (AgNO3) concentration (1-3 mg/ml) and quantity of algal extract (1-3 ml) were optimized to improve the production of AgNPs. The application of the synthesized silver nanoparticles for the adsorptive removal of copper from aqueous and industrial wastewater was investigated. Intra-particle diffusion mechanism was identified to be controlling step in metal removal. Regeneration of sorbent was carried out using 2.0 M HCl and the reusability was verified for 6 cycles. A removal efficiency of copper (64.8%) from electroplating wastewater demonstrated the industrial application potential of the synthesized silver nanoparticles.

Pharmacognosy, Phytochemistry and Pharmacological Properties of Achillea millefolium L.: A Review.

Achillea millefoilum L. (Yarrow) is an important species of Asteraceae family with common utilization in traditional medicine of several cultures from Europe to Asia for the treatment of spasmodic gastrointestinal disorders, hepatobiliary, gynecological disorders, against inflammation and for wound healing. An extensive review of literature was made on A. millefoilum L. using ethno botanical text books, published articles in peer-reviewed journals, unpublished materials and scientific databases. The Plant List, International Plant Name Index and Kew Botanical Garden databases were used to authenticate the scientific names. Monoterpenes are the most representative metabolites constituting 90% of the essential oils in relation to the sesquiterpenes, and a wide range of chemical compounds have also been reported. Different pharmacological experiments in many in-vitro and in-vivo models have proved the potential of A. millefoilum with antiinflammatory, antiulcer, anticancer activities etc. lending support to the rationale behind numerous of its traditional uses. Due to the noteworthy pharmacological activities, A. millefoilum will be a better option for new drug discovery. The present review will comprehensively summarize the pharmacognosy, phytochemistry and ethnopharmacology of A. millefoilum reported to date, with emphasis on more in vitro, clinical and pathological studies needed to investigate the unexploited potential of this plant. Copyright © 2017 John Wiley & Sons, Ltd.

Phytochemical screening of ethanolic extracts of Cuminum cyminum L. seeds along with the evaluation of antidiabetic properties by molecular docking approach.

In this contribution, ethanolic extracts of Cuminum cyminum (C. cyminum) seeds were evaluated in terms of phytochemical content, total phenol and flavonoid contents. As far as the analytical techniques are concerned, UV-Vis, FTIR, HPLC, NMR (1H and 13C) and ESI-MS were performed. The binding capacity of five different antidiabetic enzymes was tested by in silico molecular docking studies. The HPLC, UV-Vis, FTIR, NMR and ESI-MS data highlighted the presence of seven biologically active molecules e.g. α-pinene, ß-pinene, Δ3-carene, ρ-cymene, α-terpineol, cuminaldehyde and linalool. The results coming from the in silico molecular docking studies showed that such phytochemicals present in the cumin seed extracts play an important role in the activity of key enzymes involved in carbohydrate metabolism. Therefore, C. cyminum is proven to be useful for the treatment of diabetes mellitus and its major secondary complications.

Synthesis of metal-based functional nanocomposite material and its application for the elimination of paracetamol from synthetic wastewater.

Non-steroidal anti-inflammatory medicines (NSAIDs) like paracetamol and other substances released into the water system pose serious environmental issues. The current work examines the synthesis of a nanocomposite combined with Moringa olifera aqueous leaf extract as a reducing and stabilizing agent for the green synthesis of nanocomposites. Fourier Transform Infrared Spectroscopy (FTIR), X-ray Diffraction (XRD), Thermogravimetric analysis (TGA), Scanning Electron Microscope (SEM), Transmission Electron Microscope (TEM) were used to investigate metal based functional nanocomposites. The absorption band centered at a wavelength of 243 nm, which corresponds to the surface plasmon resonances of the produced nanocomposite, is confirmed in UV-vis spectra. The distinctive band at this particular wavelength is attributed to a particular group of nanocomposites based on the result from the Fourier transform infrared spectroscopy spectra. The spherical with irregularly shaped aggregates was confirmed by transmission electron microscopy, and the average size of nanoparticles was found to be 1 nm. For the elimination of pharmaceutical contaminants such as paracetamol from aqueous solutions, the adsorptive characteristics of nanocomposites were examined. Temperature, pH, adsorbent dosage, and agitation speed were investigated as adsorption parameters using Box-Behnken Design (BBD). The best removal outcomes were found under the following circumstances: temperature at 303.15 K, pH = 7.5, 0.05 g of nanocomposites at 200 rpm. Based on the adsorption study, the kinetics was found to be pseudo first order (R2 > 0.9481) which was validated and fitted by Langmuir isotherm (R2 > 0.9973). The adsorption study confirms that it was adsorbed onto the synthesized nanocomposite and found to be present on the homogeneous surface.

Larvicidal potential of Juglans regia male flower against Anopheles stephensi, Aedes aegypti and Culex quinquefasciatus.

The diseases vectored by mosquitoes continue to be a main cause of illnesses and death throughout the world. The methanol extract of Juglans regia male flower was screened for larvicidal activity against three therapeutically important mosquito vectors viz., malarial vector, Anopheles stephensi; dengue vector, Aedes aegypti and the filarial vector, Culex quinquefasciatus. The larvicidal activity was assayed against the early fourth-instar larvae of tested mosquito species at a concentration ranging from 12.5 to 200 ppm under laboratory conditions. The methanol extract recorded significant mortality against the early fourth-instar larvae of the tested species. After 12 and 24 h of exposure period, the highest effect was recorded in An. stephensi with LC50 values of 139.87 and 59.80 ppm and LC90 values of 288.96 and 166.73 ppm, respectively, followed by Ae. aegypti and Cx. quinquefasciatus. The results could be useful in search for newer, safer and more effective natural larvicidal agents.

Chicory (Cichorium intybus) and wormwood (Artemisia absinthium) extracts exhibit strong larvicidal activity against mosquito vectors of malaria, dengue fever, and filariasis.

Vector-borne diseases transmitted by mosquitoes cause globally important diseases such as malaria, dengue fever, and filariasis. The incidence of these diseases can be reduced through mosquito control programs but these control programs currently rely on synthetic insecticides that can impact the environment, and has selected widespread mosquito resistance. Environment friendly and biodegradable natural insecticides discovered in plants offer an alternative approach to mosquito control. Here, we investigated extracts from root or aerial parts of Chicory (Cichorium intybus) and wormwood (Artemisia absinthium) against the early 4th instar larvae of Anopheles stephensi (malaria vector), Aedes aegypti (dengue fever vector), and Culex quinquefasciatus (filariasis vector). The root and aerial parts extracts of A. absinthium and C. intybus at 200, 100, 50, 25 and 12.5 ppm caused significant mortality of the tested mosquito species. Root extracts exhibited higher larvicidal activity that aerial part extracts. The highest larvicidal activity was recorded in methanol extract of roots of C. intybus with LC50 = 66.16, 18.88 and LC¬90 = 197.56, 107.16 ppm for An. stephensi; LC50 = 78.51, 40.15 and LC90 = 277.31, 231.28 ppm for Ae. aegypti and LC50 = 103.99, 64.56 and LC¬90 = 314.04, 247.54 ppm for Cx. quinquefasciatus. These results reveal potent mosquito larvicidal activity against vectors of malaria, dengue fever, and filariasis is present in extracts of chicory and wormwood.

Insights into ligand selectivity in nitric oxide synthase isoforms: a molecular dynamics study.

Molecular dynamics (MD) simulations were carried out for inducible nitric oxide synthase (iNOS) and endothelial nitric oxide synthase (eNOS) isoforms complexed with substrate (L-arginine) and the iNOS specific inhibitor GW 273629, 2 for a time period of 1.2ns. The simulations were compared both within and across the isoforms. iNOS specificity of inhibitor 2 is attributed to water mediated interactions and cooperative hydrogen bond networks. Juxtaposition of the carboxylic and ammonium groups in the substrate and inhibitor serve as a modulating key in binding to the isoforms. Based on these investigations, molecules 3 and 4 were rationally designed to attain specificity among the isoforms. The capability of the designed ligands was theoretically tested through MD simulations to envisage binding patterns with both isoforms. A detailed analysis of the molecular recognition pattern shows molecule 4 to be more selective to iNOS when compared to eNOS.

Inhibition of sperm glutathione S-transferase leads to functional impairment due to membrane damage.

The role of glutathione S-transferase (GST) in the defense mechanisms of sperm is not known. We report here interference with normal motility, acrosome reaction and fertilizing ability of the goat sperm as a consequence of inhibition of GST activity. That these functional impairments were due to membrane changes was evident from the alteration in the lipid peroxidation status of these cells after GST inhibitor treatment. Increased reactive oxygen species production by the cell which occurred when GST activity was suppressed may be the mediator for membrane damage. The data argue for a role of GST in maintaining sperm membrane status.

Do antigenic peptides have a unique sense of direction inside the MHC binding groove? A molecular modelling study.

In the models suggested recently for antigenic peptides binding in the alpha 1, alpha 2 groove of MHC class I molecules, the orientation of the peptide has been shown uniquely as: the N----C vector of the peptide being parallel to the N----C vector of the alpha 1 helix of MHC. Here, we demonstrate that the reverse orientation of the peptide is equally probable. This hypothesis is supported by molecular modelling calculations and computer graphic analyses on a murine class I MHC molecule H-2Kd and its complexes with a restricted peptide RYLENGKETLQ. Analysis of the complementary interactions between the peptide residues and the amino acid side chains lining the MHC groove shows that the binding orientation of the peptide may be allele-specific and could depend on the sequence and structure of the antigenic epitope.

Carbohydrate binding specificity of the Tn-antigen binding lectin from Vicia villosa seeds (VVLB4).

2-Dansylamino-2-deoxy-D-galactose (GalNDns) is a useful fluorescent probe to study the interaction of non-fluorescent sugars with the B4 lectin from Vicia villosa seeds (VVLB4). Binding of the lectin to GalNDns leads to a 5.2-fold increase in Dansyl fluorescence with a concomitant 10 nm blue shift in its emission maximum. The strong binding of GalNDns (Ka = 7.33 x 10(4) M-1 at 20 degrees C) is due to a favourable entropic contribution to the association process. Among the other sugars studied, GalNAc alpha 1-O-Ser followed by Me alpha GalNAc are the best ligands. 2-Deoxygalactose, galactosamine and galactose are 2013, 469 and 130 times weaker ligands, respectively, as compared to GalNAc, whereas GalNDns is about 2.44 times more potent than GalNAc, indicating that substitutions at the C-2 position of GalNAc have a considerable influence on the binding affinities. Equatorial orientation of the hydroxyl group at C-3 and axial orientation at C-4 as in galactose are important for the interaction with VVLB4. The C-6 hydroxyl group is not indispensable. The binding site of the lectin is directed exclusively towards monosaccharides alone. Interestingly enough, despite its preference for Me alpha GalNAc over Me beta GalNAc, in oligosaccharides, the lectin prefers terminal beta-linked GalNAc as compared to the alpha-linked one.

Computer-aided design of selective COX-2 inhibitors: comparative molecular field analysis, comparative molecular similarity indices analysis, and docking studies of some 1,2-diarylimidazole derivatives.

Comparative molecular field analysis and comparative molecular similarity indices analysis were performed on 114 analogues of 1,2-diarylimidazole to optimize their cyclooxygenase-2 (COX-2) selective antiinflammatory activities. These studies produced models with high correlation coefficients and good predictive abilities. Docking studies were also carried out wherein these analogues were docked into the active sites of both COX-1 and COX-2 to analyze the receptor ligand interactions that confer selectivity for COX-2. The most active molecule in the series (53) adopts an orientation similar to that of SC-558 (4-[5-(4-bromophenyl)-3-trifluoromethyl-1H-1-pyrozolyl]-1-benzenesulfonamide) inside the COX-2 active site while the least active molecule (101) optimizes in a different orientation. In the active site, there are some strong hydrogen-bonding interactions observed between residues His90, Arg513, and Phe518 and the ligands. Additionally, a correlation of the quantitative structure-activity relationship data and the docking results is found to validate each other and suggests the importance of the binding step in overall drug action.

Synthesis and cyclooxygenase-2 inhibiting property of 1,5-diarylpyrazoles with substituted benzenesulfonamide moiety as pharmacophore: Preparation of sodium salt for injectable formulation.

A series of 1,5-diarylpyrazoles having a substituted benzenesulfonamide moiety as pharmacophore was synthesized and evaluated for cyclooxygenase (COX-1/COX-2) inhibitory activities. Through SAR and molecular modeling, it was found that fluorine substitution on the benzenesulfonamide moiety along with an electron-donating group at the 4-position of the 5-aryl ring yielded selectivity as well as potency for COX-2 inhibition in vitro. Among such compounds 3-fluoro-4-[5-(4-methoxyphenyl)-3-trifluoromethyl-1H-1-pyrazolyl]-1-benzenesulfonamide 3 displayed interesting pharmacokinetic properties along with antiinflammatory activity in vivo. Among the sodium salts tested in vivo, 10, the propionyl analogue of 3, showed excellent antiinflammatory activity and therefore represents a new lead structure for the development of injectable COX-2 specific inhibitors.

Theoretical studies on alpha-helix--DNA interactions.

The interaction energies between (Ala)10 and alpha-helix fragment and different nucleotide sequences in right-handed B-form have been optimized using semi-empirical potential energy functions. The energies are calculated for two different orientations of the alpha-helix, viz., when the alpha-helix axis taken in the N----C direction is (i) parallel and (ii) antiparallel to the 5'-3' ascending strand of DNA, proximal to it. When both the DNA molecule as well as the alpha-helix are treated as rigid molecules it is found that a polyalanine alpha-helix has slightly more favourable contacts when it is in the proximity of a four nucleotide sequence of 5'-(N-A-T-N)-3' type, where N is either a purine or a pyrimidine. However, when the two interacting molecules are allowed to undergo local structural variations then the interaction energy appears to be independent of the base sequence confirming the non-specific nature of these interactions.

3D-QSAR studies of indole derivatives as phosphodiesterase IV inhibitors.

The 3D-QSAR studies of some indole derivatives as phosphodiesterase (PDE) type IV inhibitors was performed by Comparative Molecular Field Analysis (CoMFA) and Comparative Molecular Similarity Indices Analysis (CoMSIA) methods to determine the factors required for the activity of these compounds. The global minimum energy conformer of the template molecule, 3 the most active molecule of the series, was obtained by simulated annealing method and used to build the structures of the molecules in the dataset. The CoMFA model produced statistically significant results with cross-validated and conventional correlation coefficients of 0.494 and 0.986 respectively. The combination of steric, electrostatic and hydrophobic fields in CoMSIA gave the best results with cross-validated and conventional correlation coefficients of 0.541 and 0.967 respectively. The predictive ability of CoMFA and CoMSIA were determined using a test set of seven indole derivatives giving predictive correlation coefficients of 0.56 and 0.59 respectively indicating good predictive power. Further, the robustness of the models was verified by bootstrapping analysis. Based upon the information derived from CoMFA and CoMSIA, we have identified some key features that may be used to design new indole derivatives and predict their PDE IV affinities prior to synthesis.

3D-QSAR studies on antitubercular thymidine monophosphate kinase inhibitors based on different alignment methods.

Three dimensional quantitative structure-activity relationship (3D-QSAR) studies were carried out on deoxythymidine monophosphate (dTMP) derivatives inhibiting thymidine monophosphate kinase (TMPK) in Mycobacterium tuberculosis. Molecular field analysis (MFA) models with three different alignment techniques, namely, least squares, pharmacophore based and receptor based methods were developed. Receptor based MFA model showed better results when compared with least squares and pharmacophore based models. The results help us to understand the nature of substituents required for activity and thereby provide guidelines to design novel and potent inhibitors as antitubercular agents.

FREE RADICAL SCAVENGING ACTIVITY OF FLAVONOID CONTAINING LEAF EXTRACTS OF Stevia rebaudiana Bert.

To evaluate the free radical scavenging activity of flavonoids containing extracts of Stevia leaf. Alcoholic. Successive butanolic and alcoholic extracts of leaves were examined for free radical scavenging activity using BHT (tert-butylhydroxytolune) as a positive control by in vitro models. Successive alcoholic extract showed remarkable free radical scavenging activity. The IC(50) was found to be 140 µg and 76 ig of successive alcoholic and BHT respectively in DPPH (2,2-diphenyl-1-picrylhydrazyl) assay method. The Dot-Blot test on silica layers also showed thescavenging activity of free radical of flavonoids containing extracts. The successive alcoholic extract shown significant antioxidant activity.

A virtual screening approach for thymidine monophosphate kinase inhibitors as antitubercular agents based on docking and pharmacophore models.

Docking and pharmacophore screening tools were used to examine the binding of ligands in the active site of thymidine monophosphate kinase of Mycobacterium tuberculosis. Docking analysis of deoxythymidine monophosphate (dTMP) analogues suggests the role of hydrogen bonding and other weak interactions in enzyme selectivity. Water-mediated hydrogen-bond networks and a halogen-bond interaction seem to stabilize the molecular recognition. A pharmacophore model was developed using 20 dTMP analogues. The pharmacophoric features were complementary to the active site residues involved in the ligand recognition. On the basis of these studies, a composite screening model that combines the features from both the docking analysis and the pharmacophore model was developed. The composite model was validated by screening a database spiked with 47 known inhibitors. The model picked up 42 of these, giving an enrichment factor of 17. The validated model was used to successfully screen an in-house database of about 500,000 compounds. Subsequent screening with other filters gave 186 hit molecules.

Barley aleurone layer cell protoplasts as a transient expression system.

Protoplasts were prepared from barley aleurone layers using 'Onozuka' cellulase digestion and purification through a Percoll gradient. Protoplasts prepared by this procedure had a viability ranging from 60% to 80% during the first two days of culture. They were responsive to gibberellic acid (GA) as measured by the stimulation of alpha-amylase synthesis. The GA stimulation was counteracted by abscisic acid (ABA). In the presence of polyethylene glycol (PEG), the protoplasts took up exogenously added plasmid DNA containing the reporter gene coding for chloramphenicol acetyl transferase (CAT) linked to a 35S promoter from cauliflower mosaic virus (CaMV) or to barley alpha-amylase gene promoters and expressed CAT activity. Therefore, barley aleurone layer protoplasts are suitable for analysis of hormone-responsive elements in hydrolase genes.