Analysis of phase stability,elastic, electronic,thermal, and optical properties of Sc1-xYxN via ab initio methods

Journal of Molecular Modeling - The recent advances in the application of machine learning to drug discovery have made it a ‘hot topic’ for research, with hundreds of academic groups...     

Molecular docking analysis of fluoroquinolones and other natural and synthetic compounds with the HCV NS3 helicase

It is of an interest to document the molecular docking analysis of fluoroquinolones and other natural and synthetic compounds with the HCV NS3 helicase. Data shows that three fluoroquinolones interacted with the NS3 helicase in the catalytic region, targeting some of the amino acids known to play a crucial role in NS3 helicase activity. Similarly, binding energy shows that the fluoroquinolones were comparable to the thiazolpiperazinyl derivatives, while superior to several of the synthetic and natural derivatives. The results show three fluoroquinolones to be potent helicase inhibitors that can be repurposed as supplemental therapy against HCV especially in cases non-responsive to DAAAs.     

Molecular dynamics simulation studies for DNA sequence recognition by reactive metabolites of anticancer compounds

The discovery of novel anticancer molecules 5F‐203 (NSC703786) and 5‐aminoflavone (5‐AMF, NSC686288) has addressed the issues of toxicity and reduced efficacy by targeting over expressed Cytochrome P450 1A1 (CYP1A1) in cancer cells. CYP1A1 metabolizes these compounds into their reactive metabolites, which are proven to mediate their anticancer effect through DNA adduct formation. However, the drug metabolite–DNA binding has not been explored so far. Hence, understanding the binding characteristics and molecular recognition for drug metabolites with DNA is of practical and fundamental interest. The present study is aimed to model binding preference shown by reactive metabolites of 5F‐203 and 5‐AMF with DNA in forming DNA adducts. To perform this, three different DNA crystal structures covering sequence diversity were selected, and 12 DNA‐reactive metabolite complexes were generated. Molecular dynamics simulations for all complexes were performed using AMBER 11 software after development of protocol for DNA‐reactive metabolite system. Furthermore, the MM‐PBSA/GBSA energy calculation, per‐nucleotide energy decomposition, and Molecular Electrostatic Surface Potential analysis were performed. The results obtained from present study clearly indicate that minor groove in DNA is preferable for binding of reactive metabolites of anticancer compounds. The binding preferences shown by reactive metabolites were also governed by specific nucleotide sequence and distribution of electrostatic charges in major and minor groove of DNA structure. Overall, our study provides useful insights into the initial step of mechanism of reactive metabolite binding to the DNA and the guidelines for designing of sequence specific DNA interacting anticancer agents. Copyright © 2014 John Wiley & Sons, Ltd.     

Elucidating Cd-mediated distinct rhizospheric and in planta ionomic and physio-biochemical responses of two contrasting Zea mays L. cultivars

Cadmium (Cd) in soil–plant system can abridge plant growth by initiating alterations in root zones. Hydroponics and rhizoboxes are useful techniques to monitor plant responses against various natural and/or induced metal stresses. However, soil based studies are considered more appropriate in order to devise efficient food safety and remediation strategies. The present research evaluated the Cd-mediated variations in elemental dynamics of rhizospheric soil together with in planta ionomics and morpho-physio-biochemical traits of two differentially Cd responsive maize cultivars. Cd-sensitive (31P41) and Cd-tolerant (3062) cultivars were grown in pots filled with 0, 20, 40, 60 and 80 µg/kg CdCl₂ supplemented soil. The results depicted that the maize cultivars significantly influenced the elemental dynamics of rhizosphere as well as in planta mineral accumulation under applied Cd stress. The uptake and translocation of N, P, K, Ca, Mg, Zn and Fe from rhizosphere and root cell sap was significantly higher in Cd stressed cv. 3062 as compared to cv. 31P41. In sensitive cultivar (31P41), Cd toxicity resulted in significantly prominent reduction of biomass, leaf area, chlorophyll, carotenoids, protein contents as well as catalase activity in comparison to tolerant one (3062). Analysis of tolerance indexes (TIs) validated that cv. 3062 exhibited advantageous growth and efficient Cd tolerance due to elevated proline, phenolics and activity of antioxidative machinery as compared to cv. 31P41. The cv. 3062 exhibited 54% and 37% less Cd bio-concentration (BCF) and translocation factors (TF), respectively in comparison to cv. 31P41 under highest Cd stress regime. Lower BCF and TF designated a higher Cd stabilization by tolerant cultivar (3062) in rhizospheric zone and its potential use in future remediation plans.     

Determination of sulpiride in pharmaceutical preparations and biological fluids using a Cr (III) enhanced chemiluminescence method

A highly sensitive and simple method for identifying sulpiride in pharmaceutical formulations and biological fluids is presented. The method is based on increased chemiluminescence (CL) intensity of a luminol–H₂O₂ system in response to the addition of Cr (III) under alkaline conditions. The CL intensity of the luminol–H₂O₂–Cr (III) system was greatly enhanced by the addition of sulpiride and the CL intensity was proportional to the concentration of sulpiride in a sample solution. Various parameters affecting the CL intensity were systematically investigated and optimized for determination of the sulpiride in a sample. Under the optimum conditions, the CL intensity was proportional to the concentration of sulpiride in the range of 0.068–4.0 µg/mL, with a good correlation coefficient of 0.997. The limit of detection (LOD) and limit of quantification (LOQ) were found to be 8.50 × 10^‐6 µg/mL and 2.83 × 10^‐5 µg/mL, respectively. The method presented here produced good reproducibility with a relative standard deviation (RSD) of 2.70% (n = 7). The effects of common excipients and metal ions were studied for their interference effect. The method was validated statistically through recovery studies and successfully applied for the determination of sulpiride in pure form, pharmaceutical preparations and spiked human plasma samples. The percentage recoveries were found to range from 99.10 to 100.05% for pure form, 98.12 to 100.18% for pharmaceutical preparations and 97.9 to 101.4% for spiked human plasma. Copyright © 2012 John Wiley & Sons, Ltd.     

Identification of chloroplast genome loci suitable for high‐resolution phylogeographic studies of Colocasia esculenta (L.) Schott (Araceae) and closely related taxa

Recently, we reported the chloroplast genome‐wide association of oligonucleotide repeats, indels and nucleotide substitutions in aroid chloroplast genomes. We hypothesized that the distribution of oligonucleotide repeat sequences in a single representative genome can be used to identify mutational hotspots and loci suitable for population genetic, phylogenetic and phylogeographic studies. Using information on the location of oligonucleotide repeats in the chloroplast genome of taro (Colocasia esculenta), we designed 30 primer pairs to amplify and sequence polymorphic loci. The primers have been tested in a range of intra‐specific to intergeneric comparisons, including ten taro samples (Colocasia esculenta) from diverse geographical locations, four other Colocasia species (C. affinis, C. fallax, C. formosana, C. gigantea) and three other aroid genera (represented by Remusatia vivipara, Alocasia brisbanensis and Amorphophallus konjac). Multiple sequence alignments for the intra‐specific comparison revealed nucleotide substitutions (point mutations) at all 30 loci and microsatellite polymorphisms at 14 loci. The primer pairs reported here reveal levels of genetic variation suitable for high‐resolution phylogeographic and evolutionary studies of taro and other closely related aroids. Our results confirm that information on repeat distribution can be used to identify loci suitable for such studies, and we expect that this approach can be used in other plant groups.     

Molten Globule of Hemoglobin Proceeds into Aggregates and Advanced Glycated End Products

Conformational alterations of bovine hemoglobin (Hb) upon sequential addition of glyoxal over a range of 0–90% v/v were investigated. At 20% v/v glyoxal, molten globule (MG) state of Hb was observed by altered tryptophan fluorescence, high ANS binding, existence of intact heme, native-like secondary structure as depicted by far-UV circular dichroism (CD) and ATR-FTIR spectra as well as loss in tertiary structure as confirmed by near-UV CD spectra. In addition, size exclusion chromatography analysis depicted that MG state at 20% v/v glyoxal corresponded to expanded pre-dissociated dimers. Aggregates of Hb were detected at 70% v/v glyoxal. These aggregates of Hb had altered tryptophan environment, low ANS binding, exposed heme, increased β-sheet secondary structure, loss in tertiary structure, enhanced thioflavin T (ThT) fluorescence and red shifted Congo Red (CR) absorbance. On incubating Hb with 30% v/v glyoxal for 0–20 days, advanced glycation end products (AGEs) were detected on day 20. These AGEs were characterised by enhanced tryptophan fluorescence at 450 nm, exposure of heme, increase in intermolecular β-sheets, enhanced ThT fluorescence and red shift in CR absorbance. Comet assay revealed aggregates and AGEs to be genotoxic in nature. Scanning electron microscopy confirmed the amorphous structure of aggregates and branched fibrils of AGEs. The transformation of α-helix to β-sheet usually alters the normal protein to amyloidogenic resulting in a variety of protein conformational disorders such as diabetes, prion and Huntington''s.     

Antioxidant,antibacterial, and catalytic performance of biosynthesized silver nanoparticles of Rhus javanica,Rumex hastatus,and Callistemon viminalis

Rhus javanica (Anacardiaceae) containing abundant glucopyranosidal constituents, is traditionally used to treat gastric and duodenal ulcer, dysentery, and diarrhea. Rumex hastatus (Polygonaceae) widely distributed in Pakistan, has traditional importance in treating wound healing, jaundice, rheumatism, and skin diseases. Callistemon viminalis (Myrtaceae), a rich source of essential oils, saponins, triterpenoids, phloroglucinols, and flavonoids is used in industries, perfumes, nutrition, and cosmetics. Taking the importance of the subject plants, this study is designed to synthesize silver nanoparticles via aqueous extracts of R. javanica (RJAgNPs), R. hastatus (RHAgNPs), and C. viminalis (CVAgNPs). Synthesis, surface, and sizes of silver nanoparticles (AgNPs) were confirmed using spectroscopic techniques including ultraviolet–visible (UV–Vis), Fourier transform-infrared (FT-IR), and scanning electron microscopy (SEM). AgNPs were produced in ratios 1:15, 1:16, and 1:9 and inferred via appearance of a sharp surface plasmon resonance (SPR) absorption peak (400–435 nm), which represented well-defined, stable, and spherical AgNPs. From SEM analysis, the sizes of RJAgNPs, RHAgNPs, and CVAgNPs were found to be 67 nm, 61 nm, and 55 nm, respectively. The synthesized AgNPs exhibited potential free radical scavenging, antibacterial, and catalytic properties in degradation of dyes including Congo red, methylene blue, methyl orange, rhodamine B, ortho and para-nitrophenols, and several food colours. Hence, the subject AgNPs in the current study might display promising role in drug development and remediation of environmental/industrial effluents.     

Role of Organic Amendments to Mitigate Cd Toxicity and Its Assimilation in <i>Triticum aestivum</i> L.

In soil biota, higher and enduring concentration of heavy metals like cadmium (Cd) is hazardous and associated with great loss in growth, yield, and quality parameters of most of the crop plants. Recently, in-situ applications of eco-friendly stabilizing agents in the form of organic modifications have been utilized to mitigate the adverse effects of Cd-toxicity. This controlled experiment was laid down to appraise the imprints of various applied organic amendments namely poultry manure (PM), farmyard manure (FYM), and sugarcane press mud (PS) to immobilize Cd in polluted soil. Moreover, phytoavailability of Cd in wheat was also accessed under an alkaline environment. Results revealed that the addition of FYM (5–10 ton ha^-1 ) in Cd-contaminated soil significantly increased germination rate, leaf chlorophyll content, plant height, spike length, biological and grain yield amongst all applied organic amendments. Moreover, the addition of FYM (5–10 ton ha^-1 ) also reduced the phytoavailability of Cd by 73–85% in the roots, 57–83% in the shoots, and 81–90% in grains of wheat crop. Thus, it is affirmed that incorporation of FYM (5–10 ton ha^-1 ) performed better to enhance wheat growth and yield by remediating Cd. Thus, the application of FYM (5–10 ton ha^-1 ) reduced the toxicity induced by Cd to plants by declining its uptake and translocation as compared to all other applied organic amendments to immobilize Cd under sandy alkaline polluted soil.