Search results for: molecular electrostatic potential (MEP)

Authors: Varsha Shinde, Belle Damodara Shenoy

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Tarballs are crude oil remnants found in oceans after long term weathering process and are a global concern since several decades as potential marine pollutant. Being complicated in structure microbial remediation of tarballs in natural environment is a slow process. They are rich in high molecular weight alkanes and poly aromatic hydrocarbons which are resistant to microbial attack and other environmental factors, therefore remain in environment for long time. However, it has been found that many bacteria and fungi inhabit on tarballs for nutrients and shelter. Many of them are supposed to be oil degraders, while others are supposed to be getting benefited by byproducts formed during hydrocarbon metabolism. Thus tarballs are forming special interesting ecological niche of microbes. This work aimed to study diversity of bacteria and fungi from tarballs and to see their potential application in crude oil degradation. The samples of tarballs were collected from Betul beach of south Goa (India). Different methods were used to isolate culturable fraction of bacteria and fungi from it. Those were sequenced for 16S rRNA gene and ITS for molecular level identification. The 16S rRNA gene sequence analysis revealed the presence of 13 bacterial genera/clades (Alcanivorax, Brevibacterium, Bacillus, Cellulomonas, Enterobacter, Klebsiella, Marinobacter, Nitratireductor, Pantoea, Pseudomonas, Pseudoxanthomonas, Tistrella and Vibrio), while the ITS sequence analysis placed the fungi in 8 diverse genera/ clades (Aspergillus, Byssochlamys, Monascus, Paecilomyces, Penicillium, Scytalidium/ Xylogone, Talaromyces and Trichoderma). All bacterial isolates were screened for oil degradation capacity. Potential strains were subjected to crude oil degradation experiment for quantification. Results were analyzed by GC-MS-MS.

Keywords: bacteria, biodegradation, crude oil, diversity, fungi, tarballs

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Authors: Rashida Rahmat Zohra, Afsheen Aman, Shah Ali Ul Qader

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Commercially important biopolymer, dextran, is enzymatically degraded into lower molecular weight fractions of vast industrial potential. Various organisms are associated with dextranase production, among which fungal, yeast and bacterial origins are used for commercial production. Dextranases are used to remove contaminating dextran in sugar processing industry and also used in oral care products for efficient removal of dental plaque. Among the hydrolytic products of dextran, isomaltooligosaccharides have prebiotic effect in humans and reduces the cariogenic effect of sucrose in oral cavity. Dextran derivatives produced by hydrolysis of high molecular polymer are also conjugated with other chemical and metallic compounds for usage in pharmaceutical, fine chemical industry, cosmetics, and food industry. Owing to the vast application of dextran and dextranases, current study focused on purification and analysis of kinetic parameters of dextranase from a newly isolated strain of Bacillus licheniformis KIBGE-IB25. Dextranase was purified up to 35.75 folds with specific activity of 1405 U/mg and molecular weight of 158 kDa. Analysis of kinetic parameters revealed that dextranase performs optimum cleavage of low molecular weight dextran (5000 Da, 0.5%) at 35ºC in 15 min at pH 4.5 with a Km and Vmax of 0.3738 mg/ml and 182.0 µmol/min, respectively. Thermal stability profiling of dextranase showed that it retained 80% activity up to 6 hours at 30-35ºC and remains 90% active at pH 4.5. In short, the dextranase reported here performs rapid cleavage of substrate at mild operational conditions which makes it an ideal candidate for dextran removal in sugar processing industry and for commercial production of low molecular weight oligosaccharides.

Keywords: Bacillus licheniformis, dextranase, gel permeation chromatograpy, enzyme purification, enzyme kinetics

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Authors: Jayanthi Sivaraman

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Claudins are the important components of the tight junctions that play a key role in paracellular permeability. Among various members of Claudin family, Claudin 4 (CLDN4) is found to be overexpressed in ovarian, pancreatic carcinomas and other epithelial malignancies. Therefore, in this study, an attempt has been made to identify potent inhibitors for CLDN4 from the ZINC database using virtual screening, molecular docking and molecular dynamics simulations. A well refined molecular model of CLDN4 was built using Prime of Schrodinger v10.2(Template- PDB ID: 4P79). Approximately, 6 million compounds from ZINC database are subjected to high-throughput virtual screening (HTVS) against the active site of CLDN4. Molecular docking using GLIDE predicted ARG31, ASN142, ASP146 and ARG158 as critically important residues. Furthermore, three compounds from ZINC database (ZINC96331839, ZINC36533519 and ZINC75819394) showed highly promising ADME properties and binding affinity with stable conformation. The therapeutic efficiency of these lead compounds is evaluated and confirmed by in-vitro and in-vivo studies which leads to the development of novel anti-cancer drugs.

Keywords: ADME property, inhibitors, molecular docking, virtual screening

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Authors: A. Monika, Manu Sharma, Hong Boo Lee, Richa Dhingra, Neelima Dhingra

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Nuclear factor-κappa B serve as a molecular lynchpin that links persistent infections and chronic inflammation to increased cancer risk. Inflammation has been recognized as a hallmark and cause of cancer. Natural products present a privileged source of inspiration for chemical probe and drug design. Herbal remedies were the first medicines used by humans due to the many pharmacologically active secondary metabolites produced by plants. Some of the metabolites like Lantadene (pentacyclic triterpenoids) from the weed Lantana camara has been known to inhibit cell division and showed anti-antitumor potential. The C-3 aromatic esters of lantadenes were synthesized, characterized and evaluated for cytotoxicity and inhibitory potential against Tumor necrosis factor alpha-induced activation of Nuclear factor-κappa B in lung cancer cell line A549. The 3-methoxybenzoyloxy substituted lead analogue inhibited kinase activity of the inhibitor of nuclear factor-kappa B kinase in a single-digit micromolar concentration. At the same time, the lead compound showed promising cytotoxicity against A549 lung cancer cells with IC50 ( half maximal inhibitory concentration) of 0.98l µM. Further, molecular docking of 3-methoxybenzoyloxy substituted analogue against Inhibitor of nuclear factor-kappa B kinase (Protein data bank ID: 3QA8) showed hydrogen bonding interaction involving oxygen atom of 3-methoxybenzoyloxy with the Arginine-31 and Glutamine-110. Encouraging results indicate the Lantadene’s potential to be developed as anticancer agents.

Keywords: anticancer, lantadenes, pentacyclic triterpenoids, weed

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Authors: Guohua Cao, Xu Dong

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X-ray Fluorescence Molecular Imaging (XFMI) holds great promise as a low-cost molecular imaging modality for biomedical applications with high chemical sensitivity. However, for in vivo biomedical applications, a key technical bottleneck is the relatively low chemical sensitivity of XFMI, especially at a reasonably low radiation dose. In laboratory x-ray source based XFMI, one of the main factors that limits the chemical sensitivity of XFMI is the scattered x-rays. We will present our latest findings on improving the chemical sensitivity of XFMI using excitation beam spectrum optimization. XFMI imaging experiments on two mouse-sized phantoms were conducted at three different excitation beam spectra. Our results show that the minimum detectable concentration (MDC) of iodine can be readily increased by five times via excitation spectrum optimization. Findings from this investigation could find use for in vivo pre-clinical small-animal XFMI in the future.

Keywords: molecular imaging, X-ray fluorescence, chemical sensitivity, X-ray scattering

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Authors: Begüm Terzi, Özlem Ateş Sönmezoğlu, Ahmet Yildirim

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Drought is the most important factor that limiting the production and productivity of wheat in the world. The yield of wheat, which is one of the most important crop in the world, reduced depend on drought. Researches to minimize effects of drought are one of the most important about breeding of drought resistant varieties. In recent years, benefiting from the drought resistance wild species and rapid advances in molecular biology studies, researches about drought have been accelerated and number of studies were made on molecular plant breeding which included the molecular mechanisms related to drought resistance. The aim of the present study was characterization of some bread wheat lines for drought tolerance which commonly cultivated in different location of Turkey. In this study, registered 9 bread wheat varieties which on the physiological tests about drought tolerance and 10 bread wheat line has been developed by Transitional Zone Agricultural Research Institute were used. SSR, STS, RAPD and SNP markers that associated with drought tolerance were used. The polymorphisms of the markers were determined by screening of two control varieties. For these purpose 40 molecular markers were used and 12 markers of them were polymorphic among the drought tolerance and the drought sensitive varieties. Control varieties were screened using polymorphic markers. All the DNAs on the genotypes will be searched for the presence of QTLs mapped to different chromosomes. Result of the research, the studied genotypes will be grouped according to drought tolerance and will be detected drought tolerance varieties by molecular markers. In addition, the results will be compared also with physiological tests. The drought tolerant wheat genotypes may be used in breeding studies related to drought stress.

Keywords: bread wheat, drought, molecular marker, Triticum aestivum

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Authors: Sharmin Sultana, Reinhard Schlickeiser

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A degenerate relativistic quantum plasma (DRQP) system (containing relativistically degenerate electrons, degenerate/non-degenerate light nuclei, and non-degenerate heavy nuclei) is considered to investigate the propagation characteristics of electrostatic solitary waves (in the ionic scale length) theoretically and numerically. The ion-acoustic solitons are found to be associated with the modified ion-acoustic waves (MIAWs) in which inertia (restoring force) is provided by mass density of the light or heavy nuclei (degenerate pressure of the cold electrons). A mechanical-motion analog (Sagdeev-type) pseudo-potential approach is adopted to study the properties of large amplitude solitary waves. The basic properties of the large amplitude MIAWs and their existence domain in terms of soliton speed (Mach number) are examined. On the other hand, a multi-scale perturbation approach, leading to an evolution equation for the envelope dynamics, is adopted to derive the cubic nonlinear Schrödinger equation (NLSE). The criteria for the occurrence of modulational instability (MI) of the MIAWs are analyzed via the nonlinear dispersion relation of the NLSE. The possibility for the formation of highly energetic localized modes (e.g. peregrine solitons, rogue waves, etc.) is predicted in such DRQP medium. Peregrine solitons or rogue waves with amplitudes of several times of the background are observed to form in DRQP. The basic features of these modulated waves (e.g. envelope solitons, peregrine solitons, and rogue waves), which are found to form in DRQP, and their MI criteria (on the basis of different intrinsic plasma parameters), are investigated. It is emphasized that our results should be useful in understanding the propagation characteristics of localized disturbances and the modulation dynamics of envelope solitons, and their instability criteria in astrophysical DRQP system (e.g. white dwarfs, neutron stars, etc., where matters under extreme conditions are assumed to exist) and also in ultra-high density experimental plasmas.

Keywords: degenerate plasma, envelope solitons, modified ion-acoustic waves, modulational instability, rogue waves

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Authors: Asli Faiza, Khamouli Saida

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With the development of computer tools over the past 20 years. Molecular modeling and, more precisely, molecular docking has very quickly entered field of pharmaceutical research. EGFR enzyme involved in cancer disease.Our work consists of studying the inhibition of EGFR (1M17) with deferent inhibitors derived from quinazoline and quinoline by molecular docking. The values of ligands L148 and L177 are the best ligands for inhibit the activity of 1M17 since it forms a stable complex with this enzyme by better binding to the active site. The results obtained show that the ligands L148 and L177 give weak interactions with the active site residues EGFR (1M17), which stabilize the complexes formed of this ligands, which gives a better binding at the level of the active site, and an RMSD of L148 [1,9563 Å] and of L177 [ 1,2483 Å]. [1, 9563, 1.2483] Å

Keywords: docking, EGFR, quinazoline, quinoliène, MOE

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Authors: Juiwen Liang, Choliang Chung

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In this study, the silicon-base oxide nanofibers with hollow structure were prepared using single-nozzle electrospinning and heat treatment. Firstly, precursor solution was prepared: the Polyvinylpyrrolidone (PVP) and Tetraethyl orthosilicate (TEOS) dissolved in ethanol and to make sure the concentration of solution in appropriate using single-nozzle electrospinning to produce the nanofibers. Secondly, control morphology of the electrostatic spinning nanofibers was conducted, and design the temperature profile to created hollow nanofibers, exploring the morphology and properties of nanofibers. The characterized of nanofibers, following instruments were used: Atomic force microscopy (AFM), Field Emission Scanning Electron Microscope (FE-SEM), Transmission electron microscopy (TEM), Photoluminescence (PL), X-ray Diffraction (XRD). The AFM was used to scan the nanofibers, and 3D Graphics were applied to explore the surface morphology of fibers. FE-SEM and TEM were used to explore the morphology and diameter of nanofibers and hollow nanofiber. The excitation and emission spectra explored by PL. Finally, XRD was used for identified crystallization of ceramic nanofibers. Using electrospinning technique followed by subsequent heat treatment, we have successfully prepared silicon-base oxide nanofibers with hollow structure. Thus, the microstructure and morphology of electrostatic spinning silicon-base oxide hollow nanofibers were explored. Major characteristics of the nanofiber in terms of crystalline, optical properties and crystal structure were identified.

Keywords: electrospinning, single-nozzle, hollow, nanofibers

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Authors: Mohamad Mohsen Yavarizadeh

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Polystyrene (PS) and related homopolymers are brittle materials that typically fail in tensile tests at very low strains. These polymers can be toughened by the addition of rubbery particles which initiate a large number of crazes that produce substantial plastic strain at relatively low stresses. Considerable energy is dissipated in the formation of these crazes, producing a relatively tough material that shows an impact toughness of more than 5 times of pure PS. While cross linking of rubbery phase is necessary in aforementioned mechanism of toughening, another mechanism of toughening was also introduced in which low molecular weight liquid rubbers can also toughen PS when dispersed in the form of small pools in the glassy matrix without any cross linking. However, this new mechanism which is based on local plasticization, fails to act properly at high strain rate deformations, i.e. impact tests. In this work, the idea of combination of these two mechanisms was tried. To do so, Polybutadiene rubbers (PB) with bimodal distribution of molecular weight were prepared in which, comparable fractions of very high and very low molecular weight rubbers were mixed. Incorporation of these materials in PS matrix in a reactive process resulted in more significant increases in toughness of PS. In other words, although low molecular weight PB is ineffective in high strain rate impact test by itself, it showed a significant synergistic effect when combined with high molecular weight PB. Surprisingly, incorporation of just 10% of low molecular weight PB doubled the impact toughness of regular high impact PS (HIPS). It was observed that most of rubbery particles could initiate crazes. The effectiveness of low molecular weight PB in impact test was attributed to low strain rate deformation of each individual craze as a result of producing a large number of crazes in this material. In other words, high molecular weight PB chains make it possible to have an appropriate dispersion of rubbery phase in order to create a large number of crazes in the PS matrix and consequently decrease the velocity of each craze. Low molecular weight PB, in turn, would have enough time to locally plasticize craze fibrils and enhance the energy dissipation.

Keywords: molecular weight distribution, polystyrene, toughness, homopolymer

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Authors: Manisha A. Hira, Arup Rakshit

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Textile substrates are endowed with flexibility and ease of making–up, but are non-conductors of electricity. Conductive materials like carbon can be incorporated into textile structures to make flexible conductive materials. Such conductive textiles find applications as electrostatic discharge materials, electromagnetic shielding materials and flexible materials to carry current or signals. This work focuses on use of carbon fiber as conductor of electricity. Carbon fibers in staple or tow form can be incorporated in textile yarn structure to conduct electricity. The paper highlights the process for development of these conductive yarns of polyester/carbon using Friction spinning (DREF) as well as ring spinning. The optimized process parameters for processing hybrid structure of polyester with carbon tow on DREF spinning and polyester with carbon staple fiber using ring spinning have been presented. The studies have been linked to highlight the electrical conductivity of the developed yarns. Further, the developed yarns have been incorporated as weft in fabric and their electrical conductivity has been evaluated. The paper demonstrates the structure and properties of fabrics developed from such polyester/carbon blend yarns and their suitability as electrically dissipative fabrics.

Keywords: carbon fiber, conductive textiles, electrostatic dissipative materials, hybrid yarns

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Authors: Geetakshi Arora, Danish Malhotra

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Diabetic wounds are serious health issues and often fail to heal, leading to limb amputation that makes the life of the patient miserable. Delayed wound healing has been characterized by an increase in matrix metalloproteinase-9 (MMP-9). Thus research throughout the world has been going on to develop selective MMP-9 inhibitors for aiding diabetic wound healing. Bioactive constituents from natural sources always served as potential leads in drug development with high rates of success. Considering the need for novel selective MMP-9 inhibitors and the importance of natural bioactive compounds in drug development, we have screened a library of bioactive constituents from plant sources that were effective in diabetic wound healing on human MMP-9 (hMMP-9) using molecular docking studies. Screened constituents are ranked according to their dock score, ∆G value (binding affinity), and Ligand efficiency evaluated from FleXX docking and Hyde scoring modules available with drug designing platform LeadIT. Rhamnocitrin showed the highest correlation between dock score, ∆G value (binding affinity), and Ligand efficiency was further explored for binding interactions with hMMP-9. The overall study suggest that Rhamnocitrin is sufficiently decorated with both hydrophilic and hydrophobic substitutions that perfectly block hMMP-9 and act as a potential lead in the design and development of selective hMMP-9 inhibitors.

Keywords: MMP-9, diabetic wound, molecular docking, phytoconstituents

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Authors: Hassan Nour, Nouh Mounadi, Oussama Abchir, Belaidi Salah, Samir Chtita

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Cholinesterase enzymes are biological catalysts essential for the transformation of acetylcholine, which is a neurotransmitter implicated in memory and learning, into acetic acid and choline, altering the neurotransmission process in Alzheimer’s disease patients. Therefore, inhibition of cholinesterase enzymes is a relevant strategy for the symptomatic treatment of Alzheimer’s disease. The current investigation aims to explore potential Cholinesterase (ChE) inhibitors through a comprehensive computational approach. Forty-nine phytoconstituents extracted from Cannabis sativa L were in-silico screened using molecular docking, pharmacokinetic and toxicological analysis to evaluate their possible inhibitory effect towards the cholinesterase enzymes. Two phytoconstituents belonging to cannabinoid derivatives were revealed to be promising candidates for Alzheimer therapy by acting as cholinesterase inhibitors. They have exhibited high binding affinities towards the cholinesterase enzymes and showed their ability to interact with key residues involved in cholinesterase enzymatic activity. In addition, they presented good ADMET profiles allowing them to be promising oral drug candidates. Furthermore, molecular dynamics (MD) simulations were executed to explore their interactions stability under mimetic biological conditions and thus support our findings. To corroborate the docking results, the binding free energy corresponding to the more stable ligand-ChE complexes was re-estimated by applying the MM-PBSA method. MD and MM-PBSA studies affirmed that the ligand-ChE recognition is spontaneous reaction leading to stable complexes. The conducted investigations have led to great findings that would strongly guide the pharmaceutical industries towards the rational development of potent anti-Alzheimer agents.

Keywords: alzheimer’s disease, molecular docking, cannabis sativa l, cholinesterase inhibitors

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Authors: Misbah Khan, Jian Wen, Muhammad Asif Shakoori

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The Organic Rankine Cycle (ORC) plays an important role in converting low-temperature heat sources into electrical power by using refrigerants as working fluids. The thermophysical properties of working fluids are essential for designing ORC. HFO-1336mzz(Z) (cis-1,1,1,4,4,4-hexafluoro-2-butene) considered as working fluid and have almost 99% low GWP and relatively same thermophysical properties used as a replacement of HFC-245fa (1,1,1,3,3-pentafluoro-propane). The environmental, safety, healthy and thermophysical properties of HFO-1336mzz(Z) are needed to use it in a practical system. In this paper, Molecular dynamics simulations were used to investigate the Homogeneous condensation, thermophysical and structural properties of HFO-1336mzz(Z) and HFC-245fa. The effect of various temperatures and pressures on thermophysical properties and condensation was extensively investigated. The liquid densities and isobaric heat capacities of this refrigerant was simulated at 273.15K to 353.15K temperatures and pressure0.5-4.0MPa. The simulation outcomes were compared with experimental data to validate our simulation method. The mean square displacement for different temperatures was investigated for dynamical analysis. The variations in potential energies and condensation rate were simulated to get insight into the condensation process. The radial distribution function was simulated at the micro level for structural analysis and revealed that the phase transition of HFO-1336mzz(Z) did not affect the intramolecular structure.

Keywords: homogenous condensation, refrigerants, molecular dynamics simulations, organic rankine cycle

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Authors: Radoslav Stojchevski, Leonid Poretsky, Dimiter Avtanski

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Proinflammatory cytokines play an important role in cancer initiation and progression by mediating the intracellular communication between the cancer cells and tumor microenvironment. Increased tumor growth causing reduced oxygen concentration and oxygen pressure commonly result in hypoxia. Mechanistically, hypoxia is characterized by stabilization and nuclear translocation of hypoxia-inducible factor 1 alpha (HIF-1α) followed by propagation of molecular pathway cascade involving multiple downstream targets. Cobalt(II) chloride (CoCl₂) is commonly used to mimic hypoxia in experimental conditions since it directly induces the expression of HIF-1α. The aim of the present study was to investigate the in vitro effects and the molecular mechanisms by which hypoxia regulates the cytokine secretory profile of breast cancer cells. As a model for this study, we used several breast cancer cell lines bearing various molecular characteristics and metastatic potential (MDA-MB-231 (clauding low, ER-/PR-/HER²⁻), MCF-7 (luminal A, ER⁺/PR⁺/HER²⁻), and BT-474 (liminal B, ER⁺/PR⁺/HER²⁺)). We demonstrated that breast cancer cells secrete numerous cytokines and cytokine ligands, including interleukins, chemokines, and growth factors. Treatment with CoCl₂significantly modulated the breast cancer cells' cytokine expression in a concentration- and time-dependent manner. These effects were mediated via activation of several signaling pathways (JNK/SAPK1, NF-κB, STAT5A/B, and Erk/MAPK1/2). Taken together, the present data define some of the molecular mechanisms by which hypoxia affects the breast cancer cells' cytokine secretory profile, thus contributing to the development of novel therapies for metastatic breast cancer.

Keywords: breast cancer, cytokines, cobalt(II) chloride (CoCl₂), hypoxia

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Authors: Ashkan Forootan, Reza Rashedi

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Polyethylene has wide usage areas such as blow molding, pipe, film, cable insulation. However, regardless to its growing applications, it has some constraints such as the limited 70C operating temperature. Polyethylene thermo setting procedure whose molecules are knotted and 3D-molecular-network formed , is developed to conquer the above problem and to raise the applicable temperature of the polymer. This paper reports the cross-linking for two different molecular weight grades of LLDPE by adding 0.5, 1, and 2% of DCP (Dicumyl Peroxide). DCP was chosen for its prevalence among various cross-linking agents. Structural parameters such as molecular weight, melt flow index, comonomer, number of branches,etc. were obtained through the use of relative tests as Gel Permeation Chromatography and Fourier Transform Infra Red spectrometer. After calculating the percentage of gel content, properties of the pure and cross-linked samples were compared by thermal and mechanical analysis with DMTA and FTIR and the effects of cross-linking like viscous and elastic modulus were discussed by using various structural paprameters such as MFI, molecular weight, short chain branches, etc. Studies showed that cross-linked polymer, unlike the pure one, had a solid state with thermal mechanical properties in the range of 110 to 120C and this helped overcome the problem of using polyethylene in temperatures near the melting point.

Keywords: LLDPE, cross-link, structural parameters, DCP, DMTA, GPC

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Authors: R. Fegas, S. Zerkout, S. Taberkokt, M. Righezza

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The present work demonstrate the potential of Betacyclodextrine (BCD) for the chiral analysis of a drug .Various separation mechanisms were applied and several parameters affecting the separation were studied, including the type and concentration of chiral selector, and pH of buffer. A simple and sensitive high-performance liquid chromatography (HPLC) method was developed as an assay for fexofenadine enantiomers in pharmaceutical preparation. Fexofenadine enantiomers were separated using a mobile phase of 0.25mM NaH2PO4–acetonitrile (65:35, v/v) – Betacyclodextrine on achiral phenyl-urea column at a flow rate of 1ml/min and measurement at 220nm. The chiral mechanism of separation was mainly based on specific interaction between the solute and the stationary phase. The retention was directly controlled by mobile phase composition but not the selectivity which results of the two mechanisms, electrostatic interactions and partition mechanism.

Keywords: fexofenadine enantiomer, HPLC, achiral phenyl-urea column

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Authors: Mala Nath, Nagamani Kompelli, Partha Roy, Snehasish Das

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Two new metal-based anticancer chemotherapeutic agents, [(Ph2Sn)2(HGuO)2(phen)Cl2] 1 and [(Ph3Sn)(HGuO)(phen)]- Cl.CH3OH.H2O 2, were designed, prepared and characterized by analytical and spectral (IR, ESI-Mass, 1H, 13C and 119Sn NMR) techniques. The proposed geometry of Sn(IV) in 1 and 2 is distorted octahedral and distorted trigonal-bipyramidal, respectively. Both 1 and 2 exhibit potential cytotoxicity in vitro against MCF-7, HepG-2 and DU-145 cell lines. The intrinsic binding constant (Kb) values of 1 (2.33 × 105 M-1) and 2 (2.46 × 105 M-1) evaluated from UV-Visible absorption studies suggest non-classical electrostatic mode of interaction via phosphate backbone of DNA double helix. The Stern-Volmer quenching constant (Ksv) of 1 (9.74 × 105 M-1) and 2 (2.9 × 106 M-1) determined by fluorescence studies suggests the groove binding and intercalation mode for 1 and 2, respectively. Effective cleavage of pBR322 DNA is induced by 1. Their interaction with DNA of cancer cells may account for potency.

Keywords: anticancer agents, DNA binding studies, NMR spectroscopy, organotin

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Authors: Alireza Jalalvand, Maryam Saleh, Somayeh Behjat Khatouni, Zahra Bahri Najafi, Foroozan Fatahinia, Narges Ismailzadeh, Behrokh Farahmand

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Object: In the last two decades, the recent outbreak of Coronavirus (SARS-CoV-2) imposed a global pandemic in the world. Despite the increasing prevalence of the disease, there are no effective drugs to treat it. A suitable and rapid way to afford an effective drug and treat the global pandemic is a computational drug study. This study used molecular docking methods to examine the potential inhibition of over 50 antiviral drugs against three fundamental proteins of SARS-CoV-2. METHODS: Through a literature review, three important proteins (a key protease, RNA-dependent RNA polymerase (RdRp), and spike) were selected as drug targets. Three-dimensional (3D) structures of protease, spike, and RdRP proteins were obtained from the Protein Data Bank. Protein had minimal energy. Over 50 antiviral drugs were considered candidates for protein inhibition and their 3D structures were obtained from drug banks. The Autodock 4.2 software was used to define the molecular docking settings and run the algorithm. RESULTS: Five drugs, including indinavir, lopinavir, saquinavir, nelfinavir, and remdesivir, exhibited the highest inhibitory potency against all three proteins based on the binding energies and drug binding positions deduced from docking and hydrogen-bonding analysis. Conclusions: According to the results, among the drugs mentioned, saquinavir and lopinavir showed the highest inhibitory potency against all three proteins compared to other drugs. It may enter laboratory phase studies as a dual-drug treatment to inhibit SARS-CoV-2.

Keywords: covid-19, drug repositioning, molecular docking, lopinavir, saquinavir

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Authors: Strahinja Z. Kovačević, Lidija R. Jevrić, Sanja O. Podunavac Kuzmanović

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The relationship between antibacterial activity of eighteen different substituted benzimidazole derivatives and their molecular characteristics was studied using chemometric QSAR (Quantitative Structure–Activity Relationships) approach. QSAR analysis has been carried out on inhibitory activity towards Staphylococcus aureus, by using molecular descriptors, as well as minimal inhibitory activity (MIC). Molecular descriptors were calculated from the optimized structures. Principal component analysis (PCA) followed by hierarchical cluster analysis (HCA) and multiple linear regression (MLR) was performed in order to select molecular descriptors that best describe the antibacterial behavior of the compounds investigated, and to determine the similarities between molecules. The HCA grouped the molecules in separated clusters which have the similar inhibitory activity. PCA showed very similar classification of molecules as the HCA, and displayed which descriptors contribute to that classification. MLR equations, that represent MIC as a function of the in silico molecular descriptors were established. The statistical significance of the estimated models was confirmed by standard statistical measures and cross-validation parameters (SD = 0.0816, F = 46.27, R = 0.9791, R2CV = 0.8266, R2adj = 0.9379, PRESS = 0.1116). These parameters indicate the possibility of application of the established chemometric models in prediction of the antibacterial behaviour of studied derivatives and structurally very similar compounds.

Keywords: antibacterial, benzimidazole, molecular descriptors, QSAR

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Authors: S. Dargouthi, S. Boughdiri, B. Tangour

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This work invoked two complementary parts. In the first, we performed a theoretical study of various dimers of molecular of titanium dioxide. Five structures were examined. Three among them, the (T), (C) and (T/P) isomers, may be considered as stable compounds because they represent absolute minima on their potential energy surfaces. (T) and (C) may coexist because they are separted by only 6.5 kcal mol-1 but (T/P) dimer is in a metastable state from an energetic point of view. Non bonded dimer (P) transforms into its homologue (O) which has been considered as transitory specie with low lifetime which evolves to (T) structure. In the second part, we highlight the possible stabilization of (T), (C) and (P) dimers by encapsulation in carbon nanotubes. This indicates the probable role that plays this transitory specie the polymerization process of molecular TiO2. Confinement is suitable to control the fast evolution process and could towards the synthesis of new titanium dioxide nanostructured materials. An alternative description of TiO2 polymorphs (Rutie, anatase et Brookite) is proposed from (T), (C) and (T/P) dimmers motifs.

Keywords: titanium dioxide, carbon nanotube, confinement. encapsulation, transitory specie

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Authors: W. Soufi, F. Boukli Hacene, S. Ghalem

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Alzheimer's disease (AD) is a neurodegenerative disease that leads to a progressive and permanent deterioration of nerve cells. This disease is progressively accompanied by an intellectual deterioration leading to psychological manifestations and behavioral disorders that lead to a loss of autonomy. It is the most frequent of degenerative dementia. Alzheimer's disease (AD), which affects a growing number of people, has become a major public health problem in a few years. In the context of the study of the mechanisms governing the evolution of AD disease, we have found that natural flavonoids are good acetylcholinesterase inhibitors that reduce the rate of ßA secretion in neurons. This work is to study the inhibition of acetylcholinesterase (AChE) which is an enzyme involved in Alzheimer's disease, by methods of molecular modeling. These results will probably help in the development of an effective therapeutic tool in the fight against the development of Alzheimer's disease. Our goal of the research is to study the inhibition of acetylcholinesterase (AChE) by molecular modeling methods.

Keywords: Alzheimer's disease, acetylcholinesterase, flavonoids, molecular modeling

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Authors: Igor B. Sivaev

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Design of molecular machines is an extraordinary growing and very important area of research that it was recognized by awarding Sauvage, Stoddart and Feringa the Nobel Prize in Chemistry in 2016 'for the design and synthesis of molecular machines'. Based on the type of motion being performed, molecular machines can be divided into two main types: molecular motors and molecular switches. Molecular switches are molecules or supramolecular complexes having bistability, i.e., the ability to exist in two or more stable forms, among which may be reversible transitions under external influence (heating, lighting, changing the medium acidity, the action of chemicals, exposure to magnetic or electric field). Molecular switches are the main structural element of any molecular electronics devices. Therefore, the design and the study of molecules and supramolecular systems capable of performing mechanical movement is an important and urgent problem of modern chemistry. There is growing interest in molecular switches and other devices of molecular electronics based on transition metal complexes; therefore choice of suitable stable organometallic unit is of great importance. An example of such unit is bis(dicarbollide) complexes of transition metals [3,3’-M(1,2-C₂B₉H₁₁)₂]ⁿ⁻. The control on the ligand rotation in such complexes can be reached by introducing substituents which could provide stabilization of certain rotamers due to specific interactions between the ligands, on the one hand, and which can participate as Lewis bases in complex formation with external metals resulting in a change in the rotation angle of the ligands, on the other hand. A series of isomeric methyl sulfide derivatives of cobalt bis(dicarbollide) complexes containing methyl sulfide substituents at boron atoms in different positions of the pentagonal face of the dicarbollide ligands [8,8’-(MeS)₂-3,3’-Co(1,2-C₂B₉H₁₀)₂]⁻, rac-[4,4’-(MeS)₂-3,3’-Co(1,2-C₂B₉H₁₀)₂]⁻ and meso-[4,7’-(MeS)₂-3,3’-Co(1,2-C₂B₉H₁₀)₂]⁻ were synthesized by the reaction of CoCl₂ with the corresponding methyl sulfide carborane derivatives [10-MeS-7,8-C₂B₉H₁₁)₂]⁻ and [10-MeS-7,8-C₂B₉H₁₁)₂]⁻. In the case of asymmetrically substituted cobalt bis(dicarbollide) complexes the corresponding rac- and meso-isomers were successfully separated by column chromatography as the tetrabutylammonium salts. The compounds obtained were studied by the methods of ¹H, ¹³C, and ¹¹B NMR spectroscopy, single crystal X-ray diffraction, cyclic voltammetry, controlled potential coulometry and quantum chemical calculations. It was found that in the solid state, the transoid- and gauche-conformations of the 8,8’- and 4,4’-isomers are stabilized by four intramolecular CH···S(Me)B hydrogen bonds each one (2.683-2.712 Å and 2.709-2.752 Å, respectively), whereas gauche-conformation of the 4,7’-isomer is stabilized by two intramolecular CH···S hydrogen bonds (2.699-2.711 Å). The existence of the intramolecular CH·S(Me)B hydrogen bonding in solutions was supported by the 1H NMR spectroscopy. These data are in a good agreement with results of the quantum chemical calculations. The corresponding iron and nickel complexes were synthesized as well. The reaction of the methyl sulfide derivatives of cobalt bis(dicarbollide) with various labile transition metal complexes results in rupture of intramolecular hydrogen bonds and complexation of the methyl sulfide groups with external metal. This results in stabilization of other rotational conformation of cobalt bis(dicarbollide) and can be used in design of molecular switches. This work was supported by the Russian Science Foundation (16-13-10331).

Keywords: molecular switches, NMR spectroscopy, single crystal X-ray diffraction, transition metal bis(dicarbollide) complexes, quantum chemical calculations

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Authors: Aliyu Adamu, Fahrul Huyop, Roswanira Abdul Wahab, Mohd Shahir Shamsir

Abstract:

Halogenated organic compounds occur in huge amount in biosphere. This is attributable to the diverse use of halogen-based compounds in the synthesis of various industrially important products. Halogenated compound is toxic and may persist in the environment, thereby causing serious health and environmental pollution problems. L-2-haloacid dehalogenases (EC 3.8.1.2) catalyse the specific cleavage of carbon-halogen bond in L-isomers of halogenated compounds, which consequently reverse the effects of environmental halogen-associated pollution. To enhance the efficiency and utility of these enzymes, this study investigates the catalytic amino acid residues and the molecular functional mechanism of DehL, by classical molecular dynamic simulations, MM-PBSA and ab initio fragments molecular orbital (FMO) calculations. The results of the study will serve as the basis for the molecular engineering of the enzyme.

Keywords: DehL, Functional mechanism, Catalytic residues, L-2-haloacid dehalogenase

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Authors: F. Boukli Hacene, W. Soufi, S. Ghalem

Abstract:

Glaucoma disease is a progressive degenerative optic neuropathy, with irreversible visual field deficits and high eye pressure being one of the risk factors. Sulfonamides are carbonic anhydrase-II inhibitors that aim to decrease the secretion of aqueous humor by direct inhibition of this enzyme at the level of the ciliary processes. These drugs present undesirable effects that are difficult to accept by the patient. In our study, we are interested in the inhibition of carbonic anhydrase-II by different natural ligands (curcumin analogues) using molecular modeling methods using molecular operating environment (MOE) software to predict their interaction with this enzyme.

Keywords: carbonic anhydrase-II, curcumin analogues, drug research, molecular modeling

Procedia PDF Downloads 61

Authors: Asima Shah, F. A. Masoodi, Adil Gani, Bilal Ahmad Ashwar

Abstract:

The present study was designed to evaluate the effect of γ-rays on the antioxidant and antiproliferative potential of β-glucan isolated from oats. The β-glucan was irradiated with 0, 2, 6, and 10 kGy by gamma ray. The samples were characterized by FT-IR, GPC, and quantitative estimation by Megazyme β-glucan assay kit. The average molecular weight of non-irradiated β-glucan was 199 kDa that decreased to 70 kDa at 10 kGy. Both FT-IR spectrum and chemical analysis revealed that the extracted β-glucan was pure having minor impurities. Antioxidant activity was evaluated by DPPH, lipid peroxidation, reducing power, metal chelating ability and oxidative DNA damage assays. Results revealed that the antioxidant activity of β-glucan increased with the increase in irradiation dose. Irradiated β-glucan also exhibited dose dependent cancer cell growth inhibition with irradiation doses. The study revealed that low molecular weight β-glucan with enhanced antioxidant and antiproliferative activities can be produced by a simple irradiation method.

Keywords: γ-irradiation, antioxidant activity, antiproliferative activity, β-glucan, oats

Procedia PDF Downloads 407

Authors: V.Barbakadze, L.Gogilashvili, L.Amiranashvili, M.Merlani, K.Mulkijanyan

Abstract:

The high-molecular fractions from the several species of two genera (Symphytum and Anchusa) of Boraginaceae family Symphytum asperum, S. caucasicum, S. officinale, and Anchusa italica were isolated. According to IR, 13C and 1H NMR, 2D heteronuclear 1H/13C HSQC spectral data and 1D NOE experiment, the main structural element of these preparations was found to be a regularly substituted polyoxyethylene, namely poly[3-(3,4-dihydroxyenyl)glyceric acid] (PDPGA) or poly[oxy-1-carboxy-2-(3,4-dihydroxyphenyl)ethylene]. Such caffeic acid-derived biopolymer to our knowledge has not been known and has been identified for the first time. This compound represents a new class of natural polyethers with a residue of 3-(3,4-dihydroxyphenyl)glyceric acid as the repeating unit. Most of the carboxylic groups of PDPGA from A. italica unlike the polymer of S. asperum, S. caucasicum, and S. officinale are methylated. The 2D DOSY experiment gave the similar diffusion coefficient for the methylated and non-methylated signals of A. italica PDPGA. Both sets of signals fell in the same horizontal. This would imply a similar molecular weight for methylated and non-methylated polymers. This was further evidenced by graphic representations of the intensity decay of the 1H signals of aromatic H-2″ and H-1 at δ 7.16 and 5.24 and that of the methoxy group at δ 3.85. These three signals essentially showed the same curve shape. According to results of in vitro and in vivo experiments PDPGA of S.asperum and S.caucasicum could be considered as potential anti-inflammatory, wound healing and anti-cancer therapeutic agent.

Keywords: caffeic acid-derived polyether, poly[3-(3, 4-dihydroxyphenyl)glyceric acid], poly[oxy-1-carboxy-2-(3, 4-dihydroxyphenyl)ethylene], symphytum, anchusa

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Authors: Ariesny Vera, Rodrigo Montecinos

Abstract:

The rare-earth elements (REEs) or rare-earth metals (REMs), correspond to seventeen chemical elements composed by the fifteen lanthanoids, as well as scandium and yttrium. Lanthanoids corresponds to lanthanum and the f-block elements, from cerium to lutetium. Scandium and yttrium are considered rare-earth elements because they have ionic radii similar to the lighter f-block elements. These elements were called rare earths because they are simply more difficult to extract and separate individually than the most metals and, generally, they do not accumulate in minerals, they are rarely found in easily mined ores and are often unfavorably distributed in common ores/minerals. REEs show unique chemical and physical properties, in comparison to the other metals in the periodic table. Nowadays, these physicochemical properties are utilized in a wide range of synthetic, catalytic, electronic, medicinal, and military applications. Because of their applications, the global demand for rare earth metals is becoming progressively more important in the transition to a self-sustaining society and greener economy. However, due to the difficult separation between lanthanoid ions, the high cost and pollution of these processes, the scientists search the development of a method that combines selectivity and quantitative separation of lanthanoids from the leaching liquor, while being more economical and environmentally friendly processes. This motivation has favored the design and development of more efficient and environmentally friendly cation extractors with the incorporation of compounds as ionic liquids, membrane inclusion polymers (PIM) and supramolecular systems. Supramolecular chemistry focuses on the development of host-guest systems, in which a host molecule can recognize and bind a certain guest molecule or ion. Normally, the formation of a host-guest complex involves non-covalent interactions Additionally, host-guest interactions can be influenced among others effects by the structural nature of host and guests. The different macrocyclic hosts for lanthanoid species that have been studied are crown ethers, cyclodextrins, cucurbituryls, calixarenes and pillararenes.Among all the factors that can influence and affect lanthanoid (III) coordination, perhaps the most basic of them is the systematic control using macrocyclic substituents that promote a selective coordination. In this sense, macrocycles pillar[n]arenes (P[n]As) present a relatively easy functionalization and they have more π-rich cavity than other host molecules. This gives to P[n]As a negative electrostatic potential in the cavity which would be responsible for the selectivity of these compounds towards cations. Furthermore, the cavity size, the linker, and the functional groups of the polar headgroups could be modified in order to control the association of lanthanoid cations. In this sense, different P[n]As systems, specifically derivatives of the pentamer P[5]A functionalized with amide, amine, phosphate and sulfate derivatives, have been designed in terms of experimental synthesis and molecular dynamics, and the interaction between these P[5]As and some lanthanoid ions such as La³+, Eu³+ and Lu³+ has been studied by physicochemical characterization by 1H-NMR, ITC and fluorescence in the case of Eu³+ systems. The molecular dynamics study of these systems was developed in hexane as solvent, also taking into account the lanthanoid ions mentioned above, and the respective comparison studies between the different ions.

Keywords: lanthanoids, macrocycles, pillar[n]arenes, rare-earth metal extraction, supramolecular chemistry, supramolecular complexes.

Procedia PDF Downloads 45

Authors: Kaining Zhang, Lang Chen, Danyang Liu, Jianying Lu, Kun Yang, Junying Wu

Abstract:

In order to solve the problem of a large amount of simulation and limited simulation scale in the first-principle molecular dynamics simulation of energetic material detonation reaction, we established an artificial intelligence model for analyzing and predicting the detonation reaction mechanism of CL-20 based on the first-principle molecular dynamics simulation of the multiscale shock technique (MSST). We employed principal component analysis to identify the dominant charge features governing molecular reactions. We adopted the K-means clustering algorithm to cluster the reaction paths and screen out the key reactions. We introduced the neural network algorithm to construct the mapping relationship between the charge characteristics of the molecular structure and the key reaction characteristics so as to establish a calculation method for predicting detonation reactions based on the charge characteristics of CL-20 and realize the rapid analysis of the reaction mechanism of energetic materials.

Keywords: energetic material detonation reaction, first-principle molecular dynamics simulation of multiscale shock technique, neural network, CL-20

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Authors: G. Agrawal, R. Agrawal, A. Pich

Abstract:

The pH and temperature responsive biodegradable poly(N-vinylcaprolactam) (PVCL) based microgels functionalized with itaconic acid (IA) units are prepared via precipitation polymerization for drug delivery applications. Volume phase transition temperature (VPTT) of the obtained microgels is influenced by both IA content and pH of the surrounding medium. The developed microgels can be degraded under acidic conditions due to the presence of hydrazone based crosslinking points inside the microgel network. The microgel particles are able to effectively encapsulate doxorubicin (DOX) drug and exhibit low drug leakage under physiological conditions. At low pH, rapid DOX release is observed due to the changes in electrostatic interactions along with the degradation of particles. The results of the cytotoxicity assay further display that the DOX-loaded microgel exhibit effective antitumor activity against HeLa cells demonstrating their great potential as drug delivery carriers for cancer therapy.

Keywords: degradable, drug delivery, hydrazone linkages, microgels, responsive

Procedia PDF Downloads 274