A common drug repositioning strategy is the re-application of an existing drug to address alternative targets. A crucial aspect to enable such repurposing is that the drug's binding site on the original target is similar to that on the alternative target. Based on the assumption that proteins with similar binding sites may bind to similar drugs, the 3D substructure similarity data can be used to identify similar sites in other proteins that are not known targets. The Drug ReposER (DRug REPOSitioning Exploration Resource) web server is designed to identify potential targets for drug repurposing based on sub-structural similarity to the binding interfaces of known drug binding sites. The application has pre-computed amino acid arrangements from protein structures in the Protein Data Bank that are similar to the 3D arrangements of known drug binding sites thus allowing users to explore them as alternative targets. Users can annotate new structures for sites that are similarly arranged to the residues found in known drug binding interfaces. The search results are presented as mappings of matched sidechain superpositions. The results of the searches can be visualized using an integrated NGL viewer. The Drug ReposER server has no access restrictions and is available at http://mfrlab.org/drugreposer/.
The present article describes the synthesis, in vitro urease inhibition and in silico molecular docking studies of a novel series of bi-heterocyclic bi-amides. The synthesis of title compounds was initiated by benzoylation, with benzoyl chloride (1), of the key starter ethyl 2-(2-amino-1,3-thiazol-4-yl)acetate (2) in weak basic aqueous medium followed by hydrazide formation, 4, and cyclization with CS2 to reach the parent bi-heterocyclic nucleophile, N-{4-[(5-sulfanyl-1,3,4-oxadiazol-2-yl)methyl]-1,3-thiazol-2-yl}benzamide (5). Various electrophiles, 8a-l, were synthesized by a two-step process and these were finally coupled with 5 to yield the targeted bi-heterocyclic bi-amide molecules, 9a-l. The structures of the newly synthesized products were corroborated by IR, 1H NMR, 13C NMR, EI-MS and elemental analysis. The in vitro screening of these molecules against urease explored that most of the compounds exhibit potent inhibitory potential against this enzyme. The compound 9j, with IC50 value of 2.58 ± 0.02 µM, exhibited most promising inhibitory activity among the series, relative to standard thiourea having IC50 value of 21.11 ± 0.12 µM. In silico studies fully augmented the experimental enzyme inhibition results. Chemo-informatics analysis showed that synthesized compounds (9a-l) mostly obeyed the Lipinski's rule. Molecular docking study suggested that ligand 9j exhibited good binding energy value (-7.10 kcal/mol) and binds within the active region of target protein. So, on the basis of present investigation, it was inferred that 9j may serve as a novel scaffold for designing more potent urease inhibitors.
Short-chain fructooligosaccharides (scFOSs) can be produced from the levan hydrolysis using levanase. Levanase from Bacillus lehensis G1 (rlevblg1) is an enzyme that specifically converts levan to scFOSs. However, the use of free levanase presents a lack of stability and reusability, thus hindering the synthesis of scFOSs for continuous reactions. Here, CLEAs for rlevblg1 were prepared and characterized. Cross-linked levanase aggregates using glutaraldehyde (CLLAs-ga) and bovine albumin serum (CLLAs-ga-bsa) showed the best activity recovery of 92.8% and 121.2%, respectively. The optimum temperature of CLLAs-ga and CLLAs-ga-bsa was increased to 35 °C and 40 °C, respectively, from its free rlevblg1 (30 °C). At high temperature (50 °C), the half-life of CLLAs-ga-bsa was higher than that of free rlevblg1 and CLLAs-ga. Both CLLAs exhibited higher stability at pH 9 and pH 10. Hyperactivation of CLLAs-ga-bsa was achieved with an effectiveness factor of more than 1 and with improved catalytic efficiency. After 3 h reaction, CLLAs-ga-bsa produced the highest total scFOSs yield of 35.4% and total sugar of 60.4% per gram levan. Finally, the reusability of CLLAs for 8 cycles with more than 50% activity retained makes them as a potential synthetic catalyst to be explored for scFOSs synthesis.
A maltogenic amylase (MAG1) from alkaliphilic Bacillus lehensis G1 was cloned, expressed in Escherichia coli, purified and characterised for its hydrolysis and transglycosylation properties. The enzyme exhibited high stability at pH values from 7.0 to 10.0. The hydrolysis of β-cyclodextrin (β-CD) produced malto-oligosaccharides of various lengths. In addition to hydrolysis, MAG1 also demonstrated transglycosylation activity for the synthesis of longer malto-oligosaccharides. The thermodynamic equilibrium of the multiple reactions was shifted towards synthesis when the reaction conditions were optimised and the water activity was suppressed, which resulted in a yield of 38% transglycosylation products consisting of malto-oligosaccharides of various lengths. Thin layer chromatography and high-performance liquid chromatography analyses revealed the presence of malto-oligosaccharides with a higher degree of polymerisation than maltoheptaose, which has never been reported for other maltogenic amylases. The addition of organic solvents into the reaction further suppressed the water activity. The increase in the transglycosylation-to-hydrolysis ratio from 1.29 to 2.15 and the increased specificity toward maltopentaose production demonstrated the enhanced synthetic property of the enzyme. The high transglycosylation activity of maltogenic amylase offers a great advantage for synthesising malto-oligosaccharides and rare carbohydrates.
The ambient sonocatalytic degradation of congo red, methyl orange, and methylene blue by titanium dioxide (TiO(2)) catalyst at initial concentrations between 10 and 50mg/L, catalyst loadings between 1.0 and 3.0mg/L and hydrogen peroxide (H(2)O(2)) concentrations up to 600 mg/L is reported. A 20 kHz ultrasonic processor at 50 W was used to accelerate the reaction. The catalysts were exposed to heat treatments between 400 and 1000 degrees C for up to 4h to induce phase change. Sonocatalysts with small amount of rutile phase showed better sonocatalytic activity but excessive rutile phase should be avoided. TiO(2) heated to 800 degrees C for 2h showed the highest sonocatalytic activity and the degradation of dyes was influenced by their chemical structures, chemical phases and characteristics of the catalysts. Congo red exhibited the highest degradation rate, attributed to multiple labile azo bonds to cause highest reactivity with the free radicals generated. An initial concentration of 10mg/L, 1.5 g/L of catalyst loading and 450 ppm of H(2)O(2) gave the best congo red removal efficiency of above 80% in 180 min. Rate coefficients for the sonocatalytic process was successfully established and the reused catalyst showed an activity drop by merely 10%.
This study explores the plausible molecular interaction between a potent hepatitis C virus inhibitor, PSI-6206 (PSI), and human serum albumin (HSA), a primary transporter in blood plasma. Results obtained from both computational viz. molecular docking and molecular dynamics (MD) simulation and wet lab techniques such as UV absorption, fluorescence, circular dichroism (CD), and atomic force microscopy (AFM) complemented each other. While docking results identified PSI binding to subdomain IIA (Site I) of HSA by forming six hydrogen bonds, MD simulations signified the complex stability throughout the 50,000 ps. A consistent cutback in the Stern-Volmer quenching constant (Ksv) along with rising temperatures supported the static mode of fluorescence quenching in response to PSI addition and implied the development of the PSI-HSA complex. This discovery was backed by the alteration of the HSA UV absorption spectrum, a larger value (>1010 M-1.s-1) of the bimolecular quenching rate constant (kq) and the AFM-guided swelling of the HSA molecule, in the presence of PSI. Moreover, the fluorescence titration results revealed a modest binding affinity (4.27-6.25×103 M-1) in the PSI-HSA system, involving hydrogen bonds, van der Waals and hydrophobic interactions, as inferred from ΔS = + 22.77 J mol-1 K-1 and ΔH = - 11.02 KJ mol-1values. CD and 3D fluorescence spectra reminded significant adjustment in the 2° and 3° structures and modification in the Tyr/Trp microenvironment of the protein in the PSI-bound state. The results obtained from drug competing experiments also advocated the binding location of PSI in HSA as Site I.
CO2 sequestration into coalbed seams is one of the practical routes for mitigating CO2 emissions. The adsorption mechanisms of CO2 onto Malaysian coals, however, are not yet investigated. In this research CO2 adsorption isotherms were first performed on dry and wet Mukah-Balingian coal samples at temperatures ranging from 300 to 348 K and pressures up to 6 MPa using volumetric technique. The dry S1 coal showed the highest CO2 adsorption capacity of 1.3 mmol g-1, at 300 K and 6 MPa among the other coal samples. The experimental results of CO2 adsorption were investigated using adsorption isotherms, thermodynamics, and kinetic models. Nonlinear analysis has been employed to investigate the data of CO2 adsorption onto coal samples via three parameter isotherm equilibrium models, namely Redlich Peterson, Koble Corrigan, Toth, Sips, and Hill, and four parameter equilibrium model, namely Jensen Seaton. The results of adsorption isotherm suggested that the Jensen Seaton model described the experimental data well. Gibb's free energy change values are negative, suggesting that CO2 adsorption onto the coal occurred randomly. Enthalpy change values in the negative range established that CO2 adsorption onto coal is an exothermic mechanism. Webber's pore-diffusion model, in particular, demonstrated that pore-diffusion was the main controlling stage in CO2 adsorption onto coal matrix. The activation energy of the coals was calculated to be below -13 kJ mol-1, indicating that adsorption of CO2 onto coals occurred through physisorption. The results demonstrate that CO2 adsorption onto coal matrix is favorable, spontaneous, and the adsorbed CO2 molecules accumulate more onto coal matrix. The observations of this investigation have significant implications for a more accurate measurement of CO2 injection into Malaysian coalbed seams.
Recent developments in the target based cancer therapies have identified HSF1 as a novel non oncogenic drug target. The present study delineates the design and molecular docking evaluation of Rohinitib (RHT) - Cantharidin (CLA) based novel HSF1 inhibitors for target-based cancer therapy. Here, we exploited the pharmacophoric features of both the parent ligands for the design of novel hybrid HSF1 inhibitors. The RHT-CLA ligands were designed and characterized for ADME/Tox features, interaction with HSF1 DNA binding domain and their pharmacophoric features essential for interaction. From the results, amino acid residues Ala17, Phe61, His63, Asn65, Ser68, Arg71 and Gln72 were found crucial for HSF1 interaction with the Heat shock elements (HSE). The hybrid ligands had better affinity towards the HSF1 DNA binding domain, in comparison to RHT or CLA and interacted with most of the active site residues. Additionally, the HSF1-ligand complex had a reduced affinity towards HSE in comparison to native HSF1. Based on the results, ligand RC15 and RC17 were non carcinogenic, non mutagenic, completely biodegradable under aerobic conditions, had better affinity for HSF1 (1.132 and 1.129 folds increase respectively) and diminished the interaction of HSF1 with HSE (1.203 and 1.239 folds decrease respectively). The simulation analysis also suggested that the ligands formed a stable complex with HSF1, restraining the movement of active site residues. In conclusion, RHT-CLA hybrid ligands can be used as a potential inhibitor of HSF1 for non-oncogene target based cancer therapy.
This work aims to apply the use of food-grade algae (FGA) composited with chitosan-benzaldehyde Schiff base biopolymer (CHA-BD) as a new adsorbent (CHA-BA/FGA) for methyl violet 2B (MV 2B) dye removal from aqueous solutions. The effect of three processing variables, including CHA-BA/FGA dosage (0.02-0.1 g/100 mL), pH solution (4-10), and contact duration (10-120 min) on the removal of MV 2B was investigated using the Box-Behnken design (BBD) model. Kinetic and equilibrium dye adsorption profiles reveal that the uptake of MV 2B dye by CHA-BA/FGA is described by the pseudo-second kinetics and the Langmuir models. The thermodynamics of the adsorption process (ΔG°, ΔH°, and ΔS°) reveal spontaneous and favorable adsorption parameters of MV 2B dye onto the CHA-BA/FGA biocomposite at ambient conditions. The CHA-BA/FGA exhibited the maximum ability to absorb MV 2B of 126.51 mg/g (operating conditions: CHA-BA/FGA dose = 0.09 g/100 mL, solution pH = 8.68, and temperature = 25 °C). Various interactions, including H-bonding, electrostatic forces, π-π stacking, and n-π stacking provide an account of the hypothesized mechanism of MV 2B adsorption onto the surface of CHA-BA/FGA. This research reveals that CHA-BA/FGA with its unique biocomposite structure and favorable adsorption properties can be used to remove harmful cationic dyes from wastewater.
The properties of fibre-reinforced composites are dependent not only on the strength of the reinforcementfibre but also on the distribution of fibre strength and the composition of the chemicals or additivesaddition within the composites. In this study, the tensile properties of abaca fibre reinforced high impactpolystyrene (HIPS) composites, which had been produced with the parameters of fibre loading (30,40,50wt.%), coupling agent maleic anhydride (MAH) (1,2,3 wt%) and impact modifier (4,5,6 wt.%) weremeasured. The optimum amount of MAH is 3% and the impact modifier is 6% and these give the besttensile properties. Meanwhile, Differential Scanning Calorimetry (DSC) was used to study the thermalbehaviour within the optimum conditions of the composites. In this research, glass transitions temperature(Tg) of neat HIPS occurred below the Tg of the optimum condition of composites as the temperature ofan amorphous state. The endothermic peak of the composites was in the range of 430-4350C, includingneat HIPS. It was observed that enthalpy of the abaca fibre reinforced HIPS composites yielded belowthe neat HIPS of 748.79 J/g.
Meranti (Philippine mahogany) sawdust, an inexpensive material, showed strong scavenging behaviour through adsorption for the removal of methylene blue (MB) from aqueous solution. Batch studies were performed to evaluate and optimize the effects of various parameters such as contact time, pH, initial dye concentrations and adsorbent dosage. Langmuir, Freundlich and Temkin isotherms were used to analyze the equilibrium data at different temperatures. The experimental data fitted well with the Langmuir adsorption isotherm, indicating thereby the mono layer adsorption of the dye. The monolayer sorption capacity of meranti sawdust for MB was found to be 120.48, 117.64, 149.25 and 158.73 mg/g at 30, 40, 50 and 60 degrees C, respectively. Thermodynamic calculations showed that the MB adsorption process is endothermic and spontaneous in nature. Kinetic studies showed that the adsorption followed a pseudo-second-order kinetic model. The results indicated that the meranti sawdust could be an alternative material in place of more costly adsorbents used for dye removal.
In this study freely suspended and Ca-alginate immobilized C. vulgaris cells were used for the biosorption of Fe(II), Mn(II), and Zn(II) ions, from the aqueous solution. Experimental data showed that biosorption capacity of algal cells was strongly dependent on the operational condition such as pH, initial metal ions concentration, dosages, contact time and temperature. The maximum biosorption of Fe(II) 43.43, Mn(II) 40.98 and Zn(II) 37.43 mg/g was achieved with Ca-alginate immobilized algal cells at optimum pH of 6.0, algal cells dosage 0.6 g/L, and contact time of 450 min at room temperature. The biosorption efficiency of freely suspended and immobilized C. vulgaris cells for heavy metals removal from the industrial wastewater was validated. Modeling of biosorption kinetics showed good agreements with pseudo-second-order. Langmuir and D-R isotherm models exhibited the best fit of experimental data. The thermodynamic parameters (ΔG°, ΔH°, and ΔS°) revealed that the biosorption of considered metal ions was feasible, spontaneous and exothermic at 25-45°C. The SEM showed porous morphology which greatly helps in the biosorption of heavy metals. The Fourier transform infrared spectrophotometer (FTIR) and X-rays Photon Spectroscopy (XPS) data spectra indicated that the functional groups predominately involved in the biosorption were C-N, -OH, COO-, -CH, C=C, C=S and -C-. These results shows that immobilized algal cells in alginate beads could potentially enhance the biosorption of considered metal ions than freely suspended cells. Furthermore, the biosorbent has significantly removed heavy metals from industrial wastewater at the optimized condition.
The adsorption of residue oil from palm oil mill effluent (POME) using chitosan powder and flake has been investigated. POME contains about 2g/l of residue oil, which has to be treated efficiently before it can be discharged. Experiments were carried out as a function of different initial concentrations of residue oil, weight dosage, contact time and pH of chitosan in powder and flake form to obtain the optimum conditions for the adsorption of residue oil from POME. The powder form of chitosan exhibited a greater rate compared to the flake type. The results obtained showed that chitosan powder, at a dosage of 0.5g/l, 15min of contact time and a pH value of 5.0, presented the most suitable conditions for the adsorption of residue oil from POME. The adsorption process performed almost 99% of residue oil removal from POME. Equilibrium studies have been carried out to determine the capacity of chitosan for the adsorption of residue oil from POME using the optimum conditions from the flocculation at different initial concentrations of residue oil. Langmuir and Freundlich adsorption models were applied to describe the experimental isotherms and isotherm constants. Equilibrium data fitted very well with the Freundlich model. The pseudo first- and second-order kinetic models and intraparticle diffusion model were used to describe the kinetic data and the rate constants were evaluated. The experimental data fitted well with the second-order kinetic model, which indicates that the chemical sorption is the rate-limiting step, i.e. chemisorption between residue oil and chitosan. The significant uptake of residue oil on chitosan was further proved by BET surface area analysis and SEM micrographs.
The biomass of Urochloa mutica was subjected to thermal degradation analyses to understand its pyrolytic behavior for bioenergy production. Thermal degradation experiments were performed at three different heating rates, 10, 30 and 50°Cmin-1 using simultaneous thermogravimetric-differential scanning calorimetric analyzer, under an inert environment. The kinetic analyses were performed using isoconversional models of Kissenger-Akahira-Sunose (KAS) and Flynn-Wall-Ozawa (FWO). The high heating value was calculated as 15.04MJmol-1. The activation energy (E) values were shown to be ranging from 103 through 233 kJmol-1. Pre-exponential factors (A) indicated the reaction to follow first order kinetics. Gibbs free energy (ΔG) was measured to be ranging from 169 to 173kJmol-1 and 168 to 172kJmol-1, calculated by KAS and FWO methods, respectively. We have shown that Para grass biomass has considerable bioenergy potential comparable to established bioenergy crops such as switchgrass and miscanthus.
The present work describes the successful functionalization/magnetization of bio-polymeric spores of Lycopodium clavatum (sporopollenin) with 1-(2-hydroxyethyl) piperazine. Analytical techniques, i.e., Fourier transform infrared (FT-IR), field emission scanning electron microscope (FESEM), energy-dispersive X-ray spectroscopy (EDS), and vibrating sample magnetometer (VSM), were used to confirm the formation of 1-(2-hydroxyethyl) piperazine-functionalized magnetic sporopollenin (MNPs-Sp-HEP). The proposed adsorbent (MNPs-Sp-HEP) was used for the removal of noxious Pb(II) and As(III) metal ions from aqueous media through a batch-wise method. Different experimental parameters were optimized for the effective removal of selected noxious metal ions. Maximum adsorption capacity (q m ) 13.36 and 69.85 mg g-1 for Pb(II) and As(III), respectively, were obtained. Thermodynamic parameters such as free energy (ΔG°), entropy (ΔS°), and enthalpy (ΔH°) were also studied from the adsorption results and were used to elaborate the mechanism of their confiscation. The obtained results indicated that newly adsorbent can be successfully applied for the decontamination of noxious Pb(II) and As(III) from the aqueous environment.
The complexation reactions between the macrocyclic ionophore, p-isopropylcalix[6]arene and Cs+ cation were studied in dimethylsulfoxide-acetonitrile (DMSO-AN) binary non-aqueous solvents at different temperatures using a conductometry method. The conductance data show that the stoichiometry of the (p-isopropylcalix[6]-arene·Cs)+ complex in all binary mixed solvents is 1:1. The stability of the complexes is affected by the composition of the binary solvent media and a non-linear behavior was observed for changes of log K(f) of the complex versus the composition of the binary mixed solvents. The thermodynamic parameters (DH°(c) and DS°(c)) for formation of (p-isopropyl-calix[6]arene·Cs)+ complex were obtained from temperature dependence of the stability constant and the obtained results show that the (p-isopropylcalix[6]arene·Cs)+ complex is enthalpy destabilized, but entropy stabilized, and the values of the mentioned parameters are affected strongly by the nature and composition of the binary mixed solvents.
Limited information is available about the thermodynamic evaluation for biomass gasification process using updraft gasifier. Therefore, to minimize errors, the gasification of dry refinery sludge (DRS) is carried out in adiabatic system at atmospheric pressure under ambient air conditions. The objectives of this paper are to investigate the physical and chemical energy and exergy of product gas at different equivalent ratios (ER). It will also be used to determine whether the cold gas, exergy, and energy efficiencies of gases may be maximized by using secondary air injected to gasification zone under various ratios (0, 0.5, 1, and 1.5) at optimum ER of 0.195. From the results obtained, it is indicated that the chemical energy and exergy of producer gas are magnified by 5 and 10 times higher than their corresponding physical values, respectively. The cold gas, energy, and exergy efficiencies of DRS gasification are in the ranges of 22.9-55.5%, 43.7-72.4%, and 42.5-50.4%, respectively. Initially, all 3 efficiencies increase until they reach a maximum at the optimum ER of 0.195; thereafter, they decline with further increase in ER values. The injection of secondary air to gasification zone is also found to increase the cold gas, energy, and exergy efficiencies. A ratio of secondary air to primary air of 0.5 is found to be the optimum ratio for all 3 efficiencies to reach the maximum values.
Lipid membranes serve as effective barriers allowing cells to maintain internal composition differing from that of extracellular medium. Membrane permeation, both natural and artificial, can take place via appearance of transversal pores. The rearrangements of lipids leading to pore formation in the intact membrane are not yet understood in details. We applied continuum elasticity theory to obtain continuous trajectory of pore formation and closure, and analyzed molecular dynamics trajectories of pre-formed pore reseal. We hypothesized that a transversal pore is preceded by a hydrophobic defect: intermediate structure spanning through the membrane, the side walls of which are partially aligned by lipid tails. This prediction was confirmed by our molecular dynamics simulations. Conversion of the hydrophobic defect into the hydrophilic pore required surmounting some energy barrier. A metastable state was found for the hydrophilic pore at the radius of a few nanometers. The dependence of the energy on radius was approximately quadratic for hydrophobic defect and small hydrophilic pore, while for large radii it depended on the radius linearly. The pore energy related to its perimeter, line tension, thus depends of the pore radius. Calculated values of the line tension for large pores were in quantitative agreement with available experimental data.
Lipid membranes are extremely stable envelopes allowing cells to survive in various environments and to maintain desired internal composition. Membrane permeation through formation of transversal pores requires substantial external stress. Practically, pores are usually formed by application of lateral tension or transmembrane voltage. Using the same approach as was used for obtaining continuous trajectory of pore formation in the stress-less membrane in the previous article, we now consider the process of pore formation under the external stress. The waiting time to pore formation proved a non-monotonous function of the lateral tension, dropping from infinity at zero tension to a minimum at the tension of several millinewtons per meter. Transmembrane voltage, on the contrary, caused the waiting time to decrease monotonously. Analysis of pore formation trajectories for several lipid species with different spontaneous curvatures and elastic moduli under various external conditions provided instrumental insights into the mechanisms underlying some experimentally observed phenomena.
Binding constants for the enantiomers of modafinil with the negatively charged chiral selector sulfated-β-CD (S-β-CD) using CE technique is presented. The calculations of the binding constants employing three different linearization plots (double reciprocal, X-reciprocal and Y-reciprocal) were performed from the electrophoretic mobility values of modafinil enantiomers at different concentrations of S-β-CD in the BGE. The highest inclusion affinity of the modafinil enantiomers were observed for the S-enantiomer-S-β-CD complex, in agreement with the computational calculations performed previously. Binding constants for each enantiomer-S-β-CD complex at different temperatures, as well as thermodynamic parameters for binding, were calculated. Host-guest binding constants using the double reciprocal fit showed better linearity (r(2)>0.99) at all temperatures studied (15-30°C) and compared with the other two fit methods. The linear van't Hoff (15-30°C) plot obtained indicated that the thermodynamic parameters of complexation were temperature dependent for the enantiomers.