A novel nano-bio composite polypyrrole (PPy)/kappa-carrageenan(KC) was fabricated and characterized for application as a cathode catalyst in a microbial fuel cell (MFC). High resolution SEM and TEM verified the bud-like shape and uniform distribution of the PPy in the KC matrix. X-ray diffraction (XRD) has approved the amorphous structure of the PPy/KC as well. The PPy/KC nano-bio composites were then studied as an electrode material, due to their oxygen reduction reaction (ORR) ability as the cathode catalyst in the MFC and the results were compared with platinum (Pt) as the most common cathode catalyst. The produced power density of the PPy/KC was 72.1 mW/m(2) while it was 46.8 mW/m(2) and 28.8 mW/m(2) for KC and PPy individually. The efficiency of the PPy/KC electrode system is slightly lower than a Pt electrode (79.9 mW/m(2)) but due to the high cost of Pt electrodes, the PPy/KC electrode system has potential to be an alternative electrode system for MFCs.
Cyanotoxins, microcystins and cylindrospermopsin, are potent toxins produced by cyanobacteria in potable water supplies. This study investigated the removal of cyanotoxins from aqueous media by magnetophoretic nanoparticle of polypyrrole adsorbent. The adsorption process was pH dependent with maximum adsorption occurring at pH 7 for microcystin-LA, LR, and YR and at pH 9 for microcystin-RR and cylindrospermopsin (CYN). Kinetic studies and adsorption isotherms reflected better fit for pseudo-second-order rate and Langmuir isotherm model, respectively. Thermodynamic calculations showed that the cyanotoxin adsorption process is endothermic and spontaneous in nature. The regenerated adsorbent can be successfully reused without appreciable loss of its original capacity.
The influence of human salivary enzymes on palm wines' odorant concentrations were investigated by the application of aroma extracts dilution analysis (AEDA) and by the calculation of odour activity values (OAVs), respectively. The odorants were quantified by means of stable isotope dilution assays (SIDA), and the degradation profiles of odorants by human saliva were also studied. Results revealed 46 odour-active compounds in the flavour dilution (FD) factor range of 4-256, and all were subsequently identified. Of the 46 odorants, 41 were identified in the Elaeis guineensis wine, 36 in Raphia hookeri wine and 29 in Borassus flabellifer wine. Among the odorants, the highest FD-factors were obtained from acetoin, 2-acetyl-1-pyrroline and 3-isobutyl-2-methoxypyrazine. Among the 13 potent odorants identified, five aroma compounds are reported here as important contributors to palm wine aroma, namely 3-isobutyl-2-methoxy-pyrazine, acetoin, 2-acetyl-1-pyrroline, 3-methylbutylacetate and ethyl hexanoate. Meanwhile, salivary enzymic degradation of odorants was more pronounced among the aldehydes, esters and thiols.
The effects of multi-walled carbon nanotube (MWNT) concentration on the structural, optical and electrical properties of conjugated polymer-carbon nanotube composite are discussed. Multi-walled carbon nanotube-polypyrrole nanocomposites were synthesized by electrochemical polymerization of monomers in the presence of different amounts of MWNTs using sodium dodecylbenzensulfonate (SDBS) as surfactant at room temperature and normal pressure. Field emission scanning electron microscopy (FESEM) indicates that the polymer is wrapped around the nanotubes. Measurement of the nonlinear refractive indices (n(2)) and the nonlinear absorption (β) of the samples with different MWNT concentrations measurements were performed by a single Z-scan method using continuous wave (CW) laser beam excitation wavelength of λ = 532 nm. The results show that both nonlinear optical parameters increased with increasing the concentration of MWNTs. The third order nonlinear susceptibilities were also calculated and found to follow the same trend as n(2) and β. In addition, the conductivity of the composite film was found to increase rapidly with the increase in the MWNT concentration.
Some novel 2,3-dioxo-5-(substituted)-arylpyrroles have been synthesized. Among these, pyrrolidine compound 1b was converted to 2,3-dioxo-5-aryl pyrrolidine 2b. Finally a set of hydrazone derivatives was obtained from the reaction of 2b with various hydrazine salts. The structures of all the new synthesized compounds were confirmed by elemental analyses, IR and 1H-NMR spectra.
One hundred and fifty-five extracts from 93 terrestrial species of plants in Peninsula Malaysia were screened for in vitro photo-cytotoxic activity by means of a cell viability test using a human leukaemia cell-line HL60. These plants which can be classified into 43 plant families are diverse in their type of vegetation and their natural habitat in the wild, and may therefore harbour equally diverse metabolites with potential pharmaceutical properties. Of these, 29 plants, namely three from each of the Clusiaceae, Leguminosae, Rutaceae and Verbenaceae families, two from the Piperaceae family and the remaining 15 are from Acanthaceae, Apocynaceae, Bignoniaceae, Celastraceae, Chrysobalanaceae, Irvingiaceae, Lauraceae, Lythraceae, Malvaceae, Meliaceae, Moraceae, Myristicaceae, Myrsinaceae, Olacaceae and Sapindaceae. Hibiscus cannabinus (Malvaceae), Ficus deltoidea (Moraceae), Maranthes corymbosa (Chrysobalanaceae), Micromelum sp., Micromelum minutum and Citrus hystrix (Rutaceae), Cryptocarya griffithiana (Lauraceae), Litchi chinensis (Sapindaceae), Scorodocarpus bornensis (Olacaceae), Kokoona reflexa (Celastraceae), Irvingia malayana (Irvingiaceae), Knema curtisii (Myristicaceae), Dysoxylum sericeum (Meliaceae), Garcinia atroviridis, Garcinia mangostana and Calophyllum inophyllum (Clusiaceae), Ervatamia hirta (Apocynaceae), Cassia alata, Entada phaseoloides and Leucaena leucocephala (Leguminosae), Oroxylum indicum (Bignoniaceae), Peronema canescens,Vitex pubescens and Premna odorata (Verbenaceae), Piper mucronatum and Piper sp. (Piperaceae), Ardisia crenata (Myrsinaceae), Lawsonia inermis (Lythraceae), Strobilanthes sp. (Acanthaceae) were able to reduce the in vitro cell viability by more than 50% when exposed to 9.6J/cm(2) of a broad spectrum light when tested at a concentration of 20 microg/mL. Six of these active extracts were further fractionated and bio-assayed to yield four photosensitisers, all of which are based on the pheophorbide-a and -b core structures. Our results suggest that the main photosensitisers from terrestrial plants are likely based on the cyclic tetrapyrrole structure and photosensitisers with other structures, if present, are present in minor amounts or are not as active as those with the cyclic tetrapyrrole structure.
Integrating polypyrrole-cellulose nanocrystal-based composites with glucose oxidase (GOx) as a new sensing regime was investigated. Polypyrrole-cellulose nanocrystal (PPy-CNC)-based composite as a novel immobilization membrane with unique physicochemical properties was found to enhance biosensor performance. Field emission scanning electron microscopy (FESEM) images showed that fibers were nanosized and porous, which is appropriate for accommodating enzymes and increasing electron transfer kinetics. The voltammetric results showed that the native structure and biocatalytic activity of GOx immobilized on the PPy-CNC nanocomposite remained and exhibited a high sensitivity (ca. 0.73 μA·mM(-1)), with a high dynamic response ranging from 1.0 to 20 mM glucose. The modified glucose biosensor exhibits a limit of detection (LOD) of (50 ± 10) µM and also excludes interfering species, such as ascorbic acid, uric acid, and cholesterol, which makes this sensor suitable for glucose determination in real samples. This sensor displays an acceptable reproducibility and stability over time. The current response was maintained over 95% of the initial value after 17 days, and the current difference measurement obtained using different electrodes provided a relative standard deviation (RSD) of 4.47%.
When a phenotype of interest is associated with an external/internal covariate, covariate inclusion in quantitative trait loci (QTL) analyses can diminish residual variation and subsequently enhance the ability of QTL detection. In the in vitro synthesis of 2-acetyl-1-pyrroline (2AP), the main fragrance compound in rice, the thermal processing during the Maillard-type reaction between proline and carbohydrate reduction produces a roasted, popcorn-like aroma. Hence, for the first time, we included the proline amino acid, an important precursor of 2AP, as a covariate in our QTL mapping analyses to precisely explore the genetic factors affecting natural variation for rice scent. Consequently, two QTLs were traced on chromosomes 4 and 8. They explained from 20% to 49% of the total aroma phenotypic variance. Additionally, by saturating the interval harboring the major QTL using gene-based primers, a putative allele of fgr (major genetic determinant of fragrance) was mapped in the QTL on the 8th chromosome in the interval RM223-SCU015RM (1.63 cM). These loci supported previous studies of different accessions. Such QTLs can be widely used by breeders in crop improvement programs and for further fine mapping. Moreover, no previous studies and findings were found on simultaneous assessment of the relationship among 2AP, proline and fragrance QTLs. Therefore, our findings can help further our understanding of the metabolomic and genetic basis of 2AP biosynthesis in aromatic rice.
Binding studies between a multi-targeted anticancer drug, sunitinib (SU) and human serum albumin (HSA) were made using fluorescence, UV-vis absorption, circular dichroism (CD) and molecular docking analysis. Both fluorescence quenching data and UV-vis absorption results suggested formation of SU-HSA complex. Moderate binding affinity between SU and HSA was evident from the value of the binding constant (3.04×104M-1), obtained at 298K. Involvement of hydrophobic interactions and hydrogen bonds as the leading intermolecular forces in the formation of SU-HSA complex was predicted from the thermodynamic data of the binding reaction. These results were in good agreement with the molecular docking analysis. Microenvironmental perturbations around Tyr and Trp residues as well as secondary and tertiary structural changes in HSA upon SU binding were evident from the three-dimensional fluorescence and circular dichroism results. SU binding to HSA also improved the thermal stability of the protein. Competitive displacement results and molecular docking analysis revealed the binding locus of SU to HSA in subdomain IIA (Sudlow's site I). The influence of a few common ions on the binding constant of SU-HSA complex was also noticed.
Magnetic solid phase extraction (MSPE) employing oil-palm fiber activated carbon (OPAC) modified with magnetite (Fe3O4) and polypyrrole (OPAC-Fe3O4-PPy) was successfully used for the determination of two organochlorine pesticides (OCPs), namely endosulfan and dieldrin in environmental water samples. Analysis was performed using gas chromatography with micro-electron capture detection (GC-μECD). The effects of three preparation variables, namely Fe3O4:OPAC ratio, amount of pyrrole monomer, and amount of FeCl3 oxidant were optimized using Box-Behnken design (BBD) (R2 < 0.99, p-value < 0.001%). The optimum conditions were as follows: Fe3O4:OPAC ratio of 2:1 w/w, 1 g of FeCl3 and 100 μL of pyrrole monomer. The experimental results obtained agreed satisfactorily with the model prediction (> 90% agreement). Optimized OPAC-Fe3O4-PPy composite was characterized using field emission scanning electron microscope, vibrating sample magnetometer and Fourier transform infrared spectroscopy. Four numerical parameters of MSPE procedure was optimized using BBD. The significance of the MSPE parameters were salt addition > sample solution pH > extraction time and desorption time. Under the optimized conditions (extraction time: 90 s, desorption time: 10 min, salt: 0%, and pH: 5.8), the method demonstrated good linearity (25-1000 ng L-1) with coefficients of determination, R2 > 0.991, and low detection limits for both endosulfan (7.3 ng L-1) and dieldrin (8.6 ng L-1). The method showed high analyte recoveries in the range of 98.6-103.5% for environmental water samples. The proposed OPAC-Fe3O4-PPy MSPE method offered good features such as sustainability, simplicity, and rapid extraction.
Bacterial infections are regarded as one of the leading causes of fatal morbidity and death in patients infected with diseases. The ability of microorganisms, particularly methicillin-resistant Staphylococcus aureus (MRSA), to develop resistance to current drugs has evoked the need for a continuous search for new drugs with better efficacies. Hence, a series of non-PAINS associated pyrrolylated-chalcones (1-15) were synthesized and evaluated for their potency against MRSA. The hydroxyl-containing compounds (8, 9, and 10) showed the most significant anti-MRSA efficiency, with the MIC and MBC values ranging from 0.08 to 0.70 mg/mL and 0.16 to 1.88 mg/mL, respectively. The time-kill curve and SEM analyses exhibited bacterial cell death within four hours after exposure to 9, suggesting its bactericidal properties. Furthermore, the docking simulation between 9 and penicillin-binding protein 2a (PBP2a, PDB ID: 6Q9N) suggests a relatively similar bonding interaction to the standard drug with a binding affinity score of -7.0 kcal/mol. Moreover, the zebrafish model showed no toxic effects in the normal embryonic development, blood vessel formation, and apoptosis when exposed to up to 40 µM of compound 9. The overall results suggest that the pyrrolylated-chalcones may be considered as a potential inhibitor in the design of new anti-MRSA agents.
Polypyrrole multi-walled carbon nanotube composite layers were used to modify the gold layer to measure heavy metal ions using the surface plasmon resonance technique. The new sensor was fabricated to detect trace amounts of mercury (Hg), lead (Pb), and iron (Fe) ions. In the present research, the sensitivity of a polypyrrole multi-walled carbon nanotube composite layer and a polypyrrole layer were compared. The application of polypyrrole multi-walled carbon nanotubes enhanced the sensitivity and accuracy of the sensor for detecting ions in an aqueous solution due to the binding of mercury, lead, and iron ions to the sensing layer. The Hg ion bonded to the sensing layer more strongly than did the Pb and Fe ions. The limitation of the sensor was calculated to be about 0.1 ppm, which produced an angle shift in the region of 0.3° to 0.6°.
Three-component reaction of a series of 1-acryloyl-3,5-bisbenzylidenepiperidin-4-ones with isatin and L-proline in 1:1:1 and 1:2:2 molar ratios in methanol afforded, respectively the piperidone-grafted novel mono- and bisspiro heterocyclic hybrids comprising functionalized piperidine, pyrrolizine and oxindole ring systems in good yields. The in vitro evaluation of cholinesterase enzymes inhibitory activity of these cycloadducts disclosed that monospiripyrrolizines (8a-k), are more active with IC50 ranging from 3.36 to 20.07 μM than either the dipolarophiles (5a-k) or bisspiropyrrolizines (9a-k). The compounds, 8i and 8e with IC50 values of 3.36 and 3.50 μM, respectively showed the maximum inhibition of acethylcholinesterase (AChE) and butrylylcholinestrase (BuChE). Molecular modeling simulation, disclosed the binding interactions of the most active compounds to the active site residues of their respective enzymes. The docking results were in accordance with the IC50 values obtained from in vitro cholinesterase assay.
Successful activation of the pyranonigrin biosynthetic gene cluster and gene knockout in Aspergillus niger plus in vivo and in vitro assays led to isolation of six new products, including a spiro cyclobutane-containing dimeric compound, which served as the basis for the proposed comprehensive pyranonigrin biosynthetic pathway. Two redox enzymes are key to forming the characteristic fused γ-pyrone core, and a protease homologue performs the exo-methylene formation.
The development of free and total cholesterol nanobiosensors based on a single step electrochemical integration of gold nanoparticles (AuNPs), cholesterol oxidase (COx), cholesterol esterase (CE) and a mediator with polypyrrole (PPy) films is described. The incorporation of the various components in the PPy films was confirmed by chronopotentiometry, cyclic voltammetry (CV), scanning electron microscopy, energy dispersive X-ray analysis (SEM-EDX), and Fourier transformed infrared (FTIR) spectroscopy. The free cholesterol, PPy-NO3--Fe(CN)64--AuNPs-COx, nanobiosensor achieved a minimum detectable concentration of 5 μM, a linear concentration range of 5-25 μM and a sensitivity of 1.6 µA cm-2 µM-1 in 0.05 M phosphate buffer (pH 7.00). For the total cholesterol, PPy-NO3--Fe(CN)64--AuNPs-COx-CE, nanobiosensor which also involved the co-incorporation of cholesterol esterase (CE) with the other components, the achieved performances include a minimum detectable total cholesterol concentration of 25 μM, a broader linear concentration range of 25-170 μM and a lower sensitivity of 0.1 µA µM-1 cm-2. Owing to its high selectivity, the presence of common interferants did not affect the total cholesterol measurement with the PPy-NO3--Fe(CN)64--AuNPs-COx-CE nanobiosensor. Both nanobiosensors were successfully used for direct and indirect determination of total cholesterol in human blood serum samples.
An efficient one-pot microwave assisted stereoselective synthesis of novel dihydro-2'H-spiro[indene-2,1'-pyrrolo[3,4-c]pyrrole]-tetraone derivatives through three-component 1,3-dipolar cycloaddition of azomethine ylides generated in situ from ninhydrin and sarcosine with a series of 1-aryl-1H-pyrrole-2,5-diones is described. The synthesised compounds were screened for their antimycobacterial and AChE inhibition activities. Compound 4b (IC50 1.30µM) has been found to display twelve fold antimycobacterial activity compared to cycloserine and it is thirty seven times more active than pyrimethamine. Compound 4h displays maximum AchE inhibitory activity with IC50 value of 0.78±0.01µmol/L.
A series of novel hybrid spiro heterocycles comprising pyrrolizine, spiroxindole and piperidine moieties was synthesized chemo-, regio- and stereoselectively in good yields from 1,3-dipolar cycloaddition reaction of a series of 1-acryloyl-3,5-bisarylmethylidenepiperidin-4-ones with azomethine ylides generated in situ from 5-choloroisatin and l-proline in methanol. These cycloadducts displayed significant cholinesterase inhibitory activity. Among the compounds screened, 8g and 8e, showed maximum inhibitory activity against acetylcholinesterase (AChE) and butyrylcholinestrase (BChE) with IC50 values of 3.33 and 3.13μM, respectively.
In search of potent anti-inflammatory agents, twenty-four chalcone derivatives including seven new compounds (13 - 17, 21 and 23) containing pyrrole moiety were designed, synthesized, and assessed for their nitric oxide (NO) and prostaglandin E2 (PGE2) suppression ability on IFN-γ/LPS-induced RAW 264.7 macrophage cells. Results showed that none of the synthesized compounds were PAINS-associated molecules, with 3-(2,5-dimethoxyphenyl)-1-(1H-pyrrol-2-yl)-prop-2-en-1-one (compound 16) exhibiting remarkable inhibition activity towards PGE2 and NO production with IC50 values of 0.5 ± 1.5 µM and 12.1 ± 1.5 µM, respectively. Physicochemical and ADMET studies showed that majority of the compounds obey to Lipinski's rule of five (RO5) having high blood brain barrier (BBB) penetration, human intestinal absorption (HIA), P- glycoprotein (PgP) inhibition and plasma binding protein (PPB) inhibition. The obtained atomic coordinates for the single-crystal XRD of 16 were then applied in a molecular docking simulation, and compound 16 was found to participate in a number of important binding interactions in the binding sites of ERK and mPGES-1. Based on these results, we have observed the potential of compound 16 as a new hit anti-inflammatory agent, and these findings could serve as a basis for further studies on its mechanism of action.
Annona muricata Linn or usually identified as soursop is a potential anticancer plant that has been widely reported to contain valuable chemopreventive agents known as annonaceous acetogenins. The antiproliferative and anticancer activities of this tropical and subtropical plant have been demonstrated in cell culture and animal studies. A. muricata L. exerts inhibition against numerous types of cancer cells, involving multiple mechanism of actions such as apoptosis, a programmed cell death that are mainly regulated by Bcl-2 family of proteins. Nonetheless, the binding mode and the molecular interactions of the plant's bioactive constituents have not yet been unveiled for most of these mechanisms. In the current study, we aim to elucidate the binding interaction of ten bioactive phytochemicals of A. muricata L. to three Bcl-2 family of antiapoptotic proteins viz. Bcl-2, Bcl-w and Mcl-1 using an in silico molecular docking analysis software, Autodock 4.2. The stability of the complex with highest affinity was evaluated using MD simulation. We compared the docking analysis of these substances with pre-clinical Bcl-2 inhibitor namely obatoclax. The study identified the potential chemopreventive agent among the bioactive compounds. We also characterized the important interacting residues of protein targets which involve in the binding interaction. Results displayed that anonaine, a benzylisoquinoline alkaloid, showed a high affinity towards the Bcl-2, thus indicating that this compound is a potent inhibitor of the Bcl-2 antiapoptotic family of proteins.