Search results for: approximation of derivatives
774 Targeting Apoptosis by Novel Adamantane Analogs as an Emerging Therapy for the Treatment of Hepatocellular Carcinoma Through EGFR, Bcl-2/BAX Cascade
Authors: Hanan M. Hassan, Laila Abouzeid, Lamya H. Al-Wahaibi, George S. G. Shehatou, Ali A. El-Emam
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Cancer is a major public health problem and the second leading cause of death worldwide. In 2020, cancer diagnosis and treatment have been negatively affected by the coronavirus 2019 (COVID-19) pandemic. During the quarantine, because of the limited access to healthcare and avoiding exposure to COVID-19 as a contagious disease; patients of cancer suffered deferments in follow-up and treatment regimens leading to substantial worsening of disease, death, and increased healthcare costs. Thus, this study is designed to investigate the molecular mechanisms by which adamantne derivatives attenuate hepatocllular carcinoma experimentally and theoretically. There is a close association between increased resistance to anticancer drugs and defective apoptosis that considered a causative factor for oncogenesis. Cancer cells use different molecular pathways to inhibit apoptosis, BAX and Bcl-2 proteins have essential roles in the progression or inhibition of intrinsic apoptotic pathways triggered by mitochondrial dysfunction. Therefore, their balance ratio can promote the cellular apoptotic fate. In this study, the in vitro cytotoxic effects of seven synthetic adamantyl isothiorea derivatives were evaluated against five human tumor cell lines by MTT assay. Compounds 5 and 6 showed the best results, mostly against hepatocellular carcinoma (HCC). Hence, in vivo studies were performed in male Sprague-Dawley (SD) rats in which experimental hepatocellular carcinoma was induced with thioacetamide (TAA) (200 mg/kg, i.p., twice weekly) for 16 weeks. The most promising compounds, 5 and 6, were administered to treat liver cancer rats at a dose of 10 mg/kg/day for an additional two weeks, and the effects were compared with doxorubicin (DR), the anticancer drug. Hepatocellular carcinoma was evidenced by a dramatic increase in liver indices, oxidative stress markers, and immunohistochemical studies that were accompanied by a plethora of inflammatory mediators and alterations in the apoptotic cascade. Our results showed that treatment with adamantane derivatives 5 and 6 significantly suppressed fibrosis, inflammation, and other histopathological insults resulting in the diminished formation of hepatocyte tumorigenesis. Moreover, administration of the tested compounds resulted in amelioration of EGFR protein expression, upregulation of BAX, and lessening down of Bcl-2 levels that prove their role as apoptosis inducers. Also, the docking simulations performed for adamantane showed good fit and binding to the EGFR protein through hydrogen bond formation with conservative amino acids, which gives a shred of strong evidence for its hepatoprotective effect. In most analyses, the effects of compound 6 were more comparable to DR than compound 5. Our findings suggest that adamantane derivatives 5 and 6 are shown to have cytotoxic activity against HCC in vitro and in vivo, by more than one mechanism, possibly by inhibiting the TLR4-MyD88-NF-κB pathway and targeting EGFR signaling.Keywords: adamantane, EGFR, HCC, apoptosis
Procedia PDF Downloads 141773 Non-Linear Assessment of Chromatographic Lipophilicity and Model Ranking of Newly Synthesized Steroid Derivatives
Authors: Milica Karadzic, Lidija Jevric, Sanja Podunavac-Kuzmanovic, Strahinja Kovacevic, Anamarija Mandic, Katarina Penov Gasi, Marija Sakac, Aleksandar Okljesa, Andrea Nikolic
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The present paper deals with chromatographic lipophilicity prediction of newly synthesized steroid derivatives. The prediction was achieved using in silico generated molecular descriptors and quantitative structure-retention relationship (QSRR) methodology with the artificial neural networks (ANN) approach. Chromatographic lipophilicity of the investigated compounds was expressed as retention factor value logk. For QSRR modeling, a feedforward back-propagation ANN with gradient descent learning algorithm was applied. Using the novel sum of ranking differences (SRD) method generated ANN models were ranked. The aim was to distinguish the most consistent QSRR model that can be found, and similarity or dissimilarity between the models that could be noticed. In this study, SRD was performed with average values of retention factor value logk as reference values. An excellent correlation between experimentally observed retention factor value logk and values predicted by the ANN was obtained with a correlation coefficient higher than 0.9890. Statistical results show that the established ANN models can be applied for required purpose. This article is based upon work from COST Action (TD1305), supported by COST (European Cooperation in Science and Technology).Keywords: artificial neural networks, liquid chromatography, molecular descriptors, steroids, sum of ranking differences
Procedia PDF Downloads 313772 Photocatalysis with Fe/Ti-Pillared Clays for the Oxofunctionalization of Alkylaromatics by O2
Authors: Houria Rezala, Jose Luis Valverde, Amaya Romero, Alessandra Molinari, Andrea Maldotti
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A pillared montmorillonite containing iron doped titania (Fe/Ti-PILC) has been prepared from a natural clay. This material has been characterized by X-ray diffraction, nitrogen adsorption, temperature programmed desorption of ammonia, inductively coupled plasma atomic emission spectroscopy, atomic absorption, and diffuse reflectance UV-VIS spectroscopy. The layer structure of Fe/Ti-PILC resulted to be ordered with an insertion of pillars, which caused a slight increase in the basal spacing of the clay. Its specific surface area was about three times larger than that of the parent Na-montmorillonite due principally to the creation of a remarkable microporous network. The doped material was a robust photocatalyst able to oxidize liquid alkyl aromatics to the corresponding carbonylic derivatives, using O2 as the oxidizing species, at mild pressure and temperature conditions. Accumulation of valuable carbonylic derivatives was possible since their over-oxidation to carbon dioxide was negligible. Fe/Ti-PILC was able to discriminate between toluene and cyclohexane in favor of the aromatic compound with an efficiency that is about three times higher than that of titanium pillared clays (Ti-PILC). It is likely that the addition of iron favored the formation of new acid sites able to interact with the aromatic substrate. Iron doping caused a significant TiO2 visible light-induced activity (wavelength > 400 nm) with only minor negative effects on its performance under UV-light irradiation (wavelength > 290 nm).Keywords: alkyl aromatics oxidation, heterogeneous photocatalysis, iron doping, pillared clays
Procedia PDF Downloads 442771 Bandgap Engineering of CsMAPbI3-xBrx Quantum Dots for Intermediate Band Solar Cell
Authors: Deborah Eric, Abbas Ahmad Khan
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Lead halide perovskites quantum dots have attracted immense scientific and technological interest for successful photovoltaic applications because of their remarkable optoelectronic properties. In this paper, we have simulated CsMAPbI3-xBrx based quantum dots to implement their use in intermediate band solar cells (IBSC). These types of materials exhibit optical and electrical properties distinct from their bulk counterparts due to quantum confinement. The conceptual framework provides a route to analyze the electronic properties of quantum dots. This layer of quantum dots optimizes the position and bandwidth of IB that lies in the forbidden region of the conventional bandgap. A three-dimensional MAPbI3 quantum dot (QD) with geometries including spherical, cubic, and conical has been embedded in the CsPbBr3 matrix. Bound energy wavefunction gives rise to miniband, which results in the formation of IB. If there is more than one miniband, then there is a possibility of having more than one IB. The optimization of QD size results in more IBs in the forbidden region. One band time-independent Schrödinger equation using the effective mass approximation with step potential barrier is solved to compute the electronic states. Envelope function approximation with BenDaniel-Duke boundary condition is used in combination with the Schrödinger equation for the calculation of eigen energies and Eigen energies are solved for the quasi-bound states using an eigenvalue study. The transfer matrix method is used to study the quantum tunneling of MAPbI3 QD through neighbor barriers of CsPbI3. Electronic states are computed using Schrödinger equation with effective mass approximation by considering quantum dot and wetting layer assembly. Results have shown the varying the quantum dot size affects the energy pinning of QD. Changes in the ground, first, second state energies have been observed. The QD is non-zero at the center and decays exponentially to zero at boundaries. Quasi-bound states are characterized by envelope functions. It has been observed that conical quantum dots have maximum ground state energy at a small radius. Increasing the wetting layer thickness exhibits energy signatures similar to bulk material for each QD size.Keywords: perovskite, intermediate bandgap, quantum dots, miniband formation
Procedia PDF Downloads 157770 Extension of the Simplified Theory of Plastic Zones for Analyzing Elastic Shakedown in a Multi-Dimensional Load Domain
Authors: Bastian Vollrath, Hartwig Hubel
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In case of over-elastic and cyclic loading, strain may accumulate due to a ratcheting mechanism until the state of shakedown is possibly achieved. Load history dependent numerical investigations by a step-by-step analysis are rather costly in terms of engineering time and numerical effort. In the case of multi-parameter loading, where various independent loadings affect the final state of shakedown, the computational effort becomes an additional challenge. Therefore, direct methods like the Simplified Theory of Plastic Zones (STPZ) are developed to solve the problem with a few linear elastic analyses. Post-shakedown quantities such as strain ranges and cyclic accumulated strains are calculated approximately by disregarding the load history. The STPZ is based on estimates of a transformed internal variable, which can be used to perform modified elastic analyses, where the elastic material parameters are modified, and initial strains are applied as modified loading, resulting in residual stresses and strains. The STPZ already turned out to work well with respect to cyclic loading between two states of loading. Usually, few linear elastic analyses are sufficient to obtain a good approximation to the post-shakedown quantities. In a multi-dimensional load domain, the approximation of the transformed internal variable transforms from a plane problem into a hyperspace problem, where time-consuming approximation methods need to be applied. Therefore, a solution restricted to structures with four stress components was developed to estimate the transformed internal variable by means of three-dimensional vector algebra. This paper presents the extension to cyclic multi-parameter loading so that an unlimited number of load cases can be taken into account. The theoretical basis and basic presumptions of the Simplified Theory of Plastic Zones are outlined for the case of elastic shakedown. The extension of the method to many load cases is explained, and a workflow of the procedure is illustrated. An example, adopting the FE-implementation of the method into ANSYS and considering multilinear hardening is given which highlights the advantages of the method compared to incremental, step-by-step analysis.Keywords: cyclic loading, direct method, elastic shakedown, multi-parameter loading, STPZ
Procedia PDF Downloads 157769 Distributed Real-Time Range Query Approximation in a Streaming Environment
Authors: Simon Keller, Rainer Mueller
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Continuous range queries are a common means to handle mobile clients in high-density areas. Most existing approaches focus on settings in which the range queries for location-based services are more or less static, whereas the mobile clients in the ranges move. We focus on a category called dynamic real-time range queries (DRRQ), assuming that both, clients requested by the query and the inquirers, are mobile. In consequence, the query parameters and the query results continuously change. This leads to two requirements: the ability to deal with an arbitrarily high number of mobile nodes (scalability) and the real-time delivery of range query results. In this paper, we present the highly decentralized solution adaptive quad streaming (AQS) for the requirements of DRRQs. AQS approximates the query results in favor of a controlled real-time delivery and guaranteed scalability. While prior works commonly optimize data structures on the involved servers, we use AQS to focus on a highly distributed cell structure without data structures automatically adapting to changing client distributions. Instead of the commonly used request-response approach, we apply a lightweight streaming method in which no bidirectional communication and no storage or maintenance of queries are required at all.Keywords: approximation of client distributions, continuous spatial range queries, mobile objects, streaming-based decentralization in spatial mobile environments
Procedia PDF Downloads 133768 Network Analysis of Genes Involved in the Biosynthesis of Medicinally Important Naphthodianthrone Derivatives of Hypericum perforatum
Authors: Nafiseh Noormohammadi, Ahmad Sobhani Najafabadi
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Hypericins (hypericin and pseudohypericin) are natural napthodianthrone derivatives produced by Hypericum perforatum (St. John’s Wort), which have many medicinal properties such as antitumor, antineoplastic, antiviral, and antidepressant activities. Production and accumulation of hypericin in the plant are influenced by both genetic and environmental conditions. Despite the existence of different high-throughput data on the plant, genetic dimensions of hypericin biosynthesis have not yet been completely understood. In this research, 21 high-quality RNA-seq data on different parts of the plant were integrated into metabolic data to reconstruct a coexpression network. Results showed that a cluster of 30 transcripts was correlated with total hypericin. The identified transcripts were divided into three main groups based on their functions, including hypericin biosynthesis genes, transporters, detoxification genes, and transcription factors (TFs). In the biosynthetic group, different isoforms of polyketide synthase (PKSs) and phenolic oxidative coupling proteins (POCPs) were identified. Phylogenetic analysis of protein sequences integrated into gene expression analysis showed that some of the POCPs seem to be very important in the biosynthetic pathway of hypericin. In the TFs group, six TFs were correlated with total hypericin. qPCR analysis of these six TFs confirmed that three of them were highly correlated. The identified genes in this research are a rich resource for further studies on the molecular breeding of H. perforatum in order to obtain varieties with high hypericin production.Keywords: hypericin, St. John’s Wort, data mining, transcription factors, secondary metabolites
Procedia PDF Downloads 84767 Effects of Hydrogen Bonding and Vinylcarbazole Derivatives on 3-Cyanovinylcarbazole Mediated Photo-Cross-Linking Induced Cytosine Deamination
Authors: Siddhant Sethi, Yasuharu Takashima, Shigetaka Nakamura, Kenzo Fujimoto
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Site-directed mutagenesis is a renowned technique to introduce specific mutations in the genome. To achieve site-directed mutagenesis, many chemical and enzymatic approaches have been reported in the past like disulphite induced genome editing, CRISPR-Cas9, TALEN etc. The chemical methods are invasive whereas the enzymatic approaches are time-consuming and expensive. Most of these techniques are unusable in the cellular application due to their toxicity and other limitations. Photo-chemical cytosine deamination, introduced in 2010, is one of the major technique for enzyme-free single-point mutation of cytosine to uracil in DNA and RNA, wherein, 3-cyanovinylcarbazole nucleoside (CNVK) containing oligodeoxyribonucleotide (ODN) having CNVK at -1 position to that of target cytosine is reversibly crosslinked to target DNA strand using 366 nm and then incubated at 90ºC to accommodate deamination. This technique is superior to enzymatic methods of site-directed mutagenesis but has a disadvantage that it requires the use of high temperature for the deamination step which restricts its applicability in the in vivo applications. This study has been focused on improving the technique by reducing the temperature required for deamination. Firstly, the photo-cross-linker, CNVK has been modified by replacing cyano group attached to vinyl group with methyl ester (OMeVK), amide (NH2VK), and carboxylic acid (OHVK) to observe the acceleration in the deamination of target cytosine cross-linked to vinylcarbazole derivative. Among the derivatives, OHVK has shown 2 times acceleration in deamination reaction as compared to CNVK, while the other two derivatives have shown deceleration towards deamination reaction. The trend of rate of deamination reaction follows the same order as that of hydrophilicity of the vinylcarbazole derivatives. OHVK being most hydrophilic has shown highest acceleration while OMeVK is least hydrophilic has proven to be least active for deamination. Secondly, in the related study, the counter-base of the target cytosine, guanine has been replaced by inosine, 2-aminopurine, nebularine, and 5-nitroindole having distinct hydrogen bonding patterns with target cytosine. Among the ODNs with these counter bases, ODN with inosine has shown 12 fold acceleration towards deamination of cytosine cross-linked to CNVK at physiological conditions as compared to guanosine. Whereas, when 2-aminopurine, nebularine, and 5-nitroindole were used, no deamination reaction took place. It can be concluded that inosine has potential to be used as the counter base of target cytosine for the CNVK mediated photo-cross-linking induced deamination of cytosine. The increase in rate of deamination reaction has been attributed to pattern and number of hydrogen bonding between the cytosine and counter base. One of the important factor is presence of hydrogen bond between exo-cyclic amino group of cytosine and the counter base. These results will be useful for development of more efficient technique for site-directed mutagenesis for C → U transformations in the DNA/RNA which might be used in the living system for treatment of various genetic disorders and genome engineering for making designer and non-native proteins.Keywords: C to U transformation, DNA editing, genome engineering, ultra-fast photo-cross-linking
Procedia PDF Downloads 228766 Fast Approximate Bayesian Contextual Cold Start Learning (FAB-COST)
Authors: Jack R. McKenzie, Peter A. Appleby, Thomas House, Neil Walton
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Cold-start is a notoriously difficult problem which can occur in recommendation systems, and arises when there is insufficient information to draw inferences for users or items. To address this challenge, a contextual bandit algorithm – the Fast Approximate Bayesian Contextual Cold Start Learning algorithm (FAB-COST) – is proposed, which is designed to provide improved accuracy compared to the traditionally used Laplace approximation in the logistic contextual bandit, while controlling both algorithmic complexity and computational cost. To this end, FAB-COST uses a combination of two moment projection variational methods: Expectation Propagation (EP), which performs well at the cold start, but becomes slow as the amount of data increases; and Assumed Density Filtering (ADF), which has slower growth of computational cost with data size but requires more data to obtain an acceptable level of accuracy. By switching from EP to ADF when the dataset becomes large, it is able to exploit their complementary strengths. The empirical justification for FAB-COST is presented, and systematically compared to other approaches on simulated data. In a benchmark against the Laplace approximation on real data consisting of over 670, 000 impressions from autotrader.co.uk, FAB-COST demonstrates at one point increase of over 16% in user clicks. On the basis of these results, it is argued that FAB-COST is likely to be an attractive approach to cold-start recommendation systems in a variety of contexts.Keywords: cold-start learning, expectation propagation, multi-armed bandits, Thompson Sampling, variational inference
Procedia PDF Downloads 103765 Tuning the Emission Colour of Phenothiazine by Introduction of Withdrawing Electron Groups
Authors: Andrei Bejan, Luminita Marin, Dalila Belei
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Phenothiazine with electron-rich nitrogen and sulfur heteroatoms has a high electron-donating ability which promotes a good conjugation and therefore low band-gap with consequences upon charge carrier mobility improving and shifting of light emission in visible domain. Moreover, its non-planar butterfly conformation inhibits molecular aggregation and thus preserves quite well the fluorescence quantum yield in solid state compared to solution. Therefore phenothiazine and its derivatives are promising hole transport materials for use in organic electronic and optoelectronic devices as light emitting diodes, photovoltaic cells, integrated circuit sensors or driving circuits for large area display devices. The objective of this paper was to obtain a series of new phenothiazine derivatives by introduction of different electron withdrawing substituents as formyl, carboxyl and cyanoacryl units in order to create a push pull system which has potential to improve the electronic and optical properties. Bromine atom was used as electrono-donor moiety to extend furthermore the existing conjugation. The understudy compounds were structural characterized by FTIR and 1H-NMR spectroscopy and single crystal X-ray diffraction. Besides, the single crystal X-ray diffraction brought information regarding the supramolecular architecture of the compounds. Photophysical properties were monitored by UV-vis and photoluminescence spectroscopy, while the electrochemical behavior was established by cyclic voltammetry. The absorption maxima of the studied compounds vary in a large range (322-455 nm), reflecting the different electronic delocalization degree, depending by the substituent nature. In a similar manner, the emission spectra reveal different color of emitted light, a red shift being evident for the groups with higher electron withdrawing ability. The emitted light is pure and saturated for the compounds containing strong withdrawing formyl or cyanoacryl units and reach the highest quantum yield of 71% for the compound containing bromine and cyanoacrilic units. Electrochemical study show reversible oxidative and reduction processes for all the compounds and a close correlation of the HOMO-LUMO band gap with substituent nature. All these findings suggest the obtained compounds as promising materials for optoelectronic devices.Keywords: electrochemical properties, phenothiazine derivatives, photoluminescence, quantum yield
Procedia PDF Downloads 328764 Novel Inference Algorithm for Gaussian Process Classification Model with Multiclass and Its Application to Human Action Classification
Authors: Wanhyun Cho, Soonja Kang, Sangkyoon Kim, Soonyoung Park
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In this paper, we propose a novel inference algorithm for the multi-class Gaussian process classification model that can be used in the field of human behavior recognition. This algorithm can drive simultaneously both a posterior distribution of a latent function and estimators of hyper-parameters in a Gaussian process classification model with multi-class. Our algorithm is based on the Laplace approximation (LA) technique and variational EM framework. This is performed in two steps: called expectation and maximization steps. First, in the expectation step, using the Bayesian formula and LA technique, we derive approximately the posterior distribution of the latent function indicating the possibility that each observation belongs to a certain class in the Gaussian process classification model. Second, in the maximization step, using a derived posterior distribution of latent function, we compute the maximum likelihood estimator for hyper-parameters of a covariance matrix necessary to define prior distribution for latent function. These two steps iteratively repeat until a convergence condition satisfies. Moreover, we apply the proposed algorithm with human action classification problem using a public database, namely, the KTH human action data set. Experimental results reveal that the proposed algorithm shows good performance on this data set.Keywords: bayesian rule, gaussian process classification model with multiclass, gaussian process prior, human action classification, laplace approximation, variational EM algorithm
Procedia PDF Downloads 329763 Magnetic and Optical Properties of GaFeMnN
Authors: A.Abbad, H.A.Bentounes, W.Benstaali
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The full-potential linearized augmented plane wave method (FP-LAPW) within the Generalized Gradient Approximation (GGA) is used to calculate the magnetic and optical properties of quaternary GaFeMnN. The results show that the compound becomes magnetic and half metallic and there is an apparition of peaks at low frequencies for the optical properties.Keywords: FP-LAPW, LSDA, magnetic moment, reflectivity
Procedia PDF Downloads 518762 Exploring the Dynamics in the EU-Association of Southeast Asia Nations Interregional Relationship, 2012-2017
Authors: Xuechen Chen
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The EU-ASEAN relations which can be dated back to 1972 represents one of the oldest group-to-group relationship in international politics. Despite a longstanding dialogue partnership, the EU and ASEAN have long been reluctant to forge deeper and substantial cooperation in political and security domains. However, the year of 2012 witnessed a salient shift in EU-ASEAN relations, with the EU significantly elevating ASEAN's profile in its external relations. Given the limited scholarly attention that has been devoted to this change in ASEAN-EU relations, this article explores why there has been a greater level of engagement and approximation between the EU and ASEAN. In particular, it asks why the EU, which had long been reluctant to recognize ASEAN as a strategic partner, has changed its policy towards ASEAN. Drawing on social constructivism, this article argues that the EU’s and ASEAN’s evolving identity-formation processes have played a significant role in reshaping their mutual perceptions, which subsequently leads to the modification of the interregional policies of both actors. The methodology of this study is based on content analysis of a wide range of official documents and policy papers from the EU and ASEAN, as well as more than 20 in-depth elite interviews with diplomats and experts working on the EU-ASEAN relationship from both organisations. Departing from the existing works which mainly adopt a Eurocentric perspective when analysing the EU-ASEAN interregionalism, this study suggests that the approximation of the EU-ASEAN relationship between 2012 and 2017 is driven by both actors’ adjustment of international identities, together with the internal dynamics and systematic changes within both regions.Keywords: Association of Southeast Asia Nations, European Union, EU foreign policy, interregionalism
Procedia PDF Downloads 141761 Design and Synthesis of Some Oxadiazole Bearing Benzimidazole Derivatives as Potential Epidermal Growth Factor Receptor Inhibitors
Authors: Ismail Celik, Gulgun Ayhan Kilcigil, Berna Guven, Zumra Kara, Arzu Onay-Besikci
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Epidermal Growth Factor Receptor is the cell-surface receptor of the ErbB (erythroblastic leukemia viral oncogene homologue receptors) family of tyrosine kinases. It plays a vital role in regulating the proliferation and differentiation of cells. However, a variety of mechanisms, such as EGFR expression, mutation, and ligand-dependent receptor dimerization, are associated with the development of various activated EGFR tumors. EGFR is highly expressed in most solid tumors, including breast, head and neck cancer, non-small cell lung cancer (NSCLC), renal, ovarian, and colon cancers. Thus, specific EGFR inhibition plays one of the key roles in cancer treatment. The compounds used in the treatment as tyrosine kinase inhibitors are known to contain the benzimidazole isosterium indole, pazopanib, and axitinibin indazole rings. In addition, benzimidazoles have been shown to exhibit protein kinase inhibitory activity in addition to their different biological activities.Based on these data, it was planned and synthesized of some oxadiazole bearing benzimidazole derivatives [N-cyclohexyl-5-((2-phenyl/substitutedphenyl-1H-benzo[d]imidazole-1-yl) methyl)-1,3,4-oxadiazole-2-amine]. EGFR kinase inhibitory efficiency of the synthesized compounds was determined by comparing them with a known kinase inhibitor erlotinib in vitro, and two of the compounds bearing phenyl (19a) and 3,4-dibenzyloxyphenyl (21a) ring exhibited significant activities.Keywords: benzimidazole, EGFR kinase inhibitory, oxadiazole, synthesis
Procedia PDF Downloads 131760 Assessment of Isatin as Surface Recognition Group: Design, Synthesis and Anticancer Evaluation of Hydroxamates as Novel Histone Deacetylase Inhibitors
Authors: Harish Rajak, Kamlesh Raghuwanshi
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Histone deacetylase (HDAC) are promising target for cancer treatment. The panobinostat (Farydak; Novartis; approved by USFDA in 2015) and chidamide (Epidaza; Chipscreen Biosciences; approved by China FDA in 2014) are the novel HDAC inhibitors ratified for the treatment of patients with multiple myeloma and peripheral T cell lymphoma, respectively. On the other hand, two other HDAC inhibitors, Vorinostat (SAHA; approved by USFDA in 2006) and Romidepsin (FK228; approved by USFDA in 2009) are already in market for the treatment of cutaneous T-cell lymphoma. Several hydroxamic acid based HDAC inhibitors i.e., belinostat, givinostat, PCI24781 and JNJ26481585 are in clinical trials. HDAC inhibitors consist of three pharmacophoric features - an aromatic cap group, zinc binding group (ZBG) and a linker chain connecting cap group to ZBG. Herein, we report synthesis, characterization and biological evaluation of HDAC inhibitors possessing substituted isatin moiety as cap group which recognize the surface of active enzyme pocket and thiosemicarbazide moiety incorporated as linker group responsible for connecting cap group to ZBG (hydroxamic acid). Several analogues were found to inhibit HDAC and cellular proliferation of Hela cervical cancer cells with GI50 values in the micro molar range. Some of the compounds exhibited promising results in vitro antiproliferative studies. Attempts were also made to establish the structure activity relationship among synthesized HDAC inhibitors.Keywords: HDAC inhibitors, hydroxamic acid derivatives, isatin derivatives, antiproliferative activity, docking
Procedia PDF Downloads 304759 Approximation of a Wanted Flow via Topological Sensitivity Analysis
Authors: Mohamed Abdelwahed
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We propose an optimization algorithm for the geometric control of fluid flow. The used approach is based on the topological sensitivity analysis method. It consists in studying the variation of a cost function with respect to the insertion of a small obstacle in the domain. Some theoretical and numerical results are presented in 2D and 3D.Keywords: sensitivity analysis, topological gradient, shape optimization, stokes equations
Procedia PDF Downloads 531758 The Use of Polar Substituent Groups for Promoting Azo Disperse Dye Solubility and Reactivity for More Economic and Environmental Benign Applications: A Computational Study
Authors: Olaide O. Wahab, Lukman O. Olasunkanmi, Krishna K. Govender, Penny P. Govender
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The economic and environmental challenges associated with azo disperse dyes applications are due to poor aqueous solubility and low degradation tendency which stems from low chemical reactivity. Poor aqueous solubility property of this group of dyes necessitates the use of dispersing agents which increase operational costs and also release toxic chemical components into the environment, while their low degradation tendency is due to the high stability of the azo functional group (-N=N-) in their chemical structures. To address these problems, this study investigated theoretically the effects of some polar substituents on the aqueous solubility and reactivity properties of disperse yellow (DY) 119 dye with a view to theoretically develop new azo disperse dyes with improved solubility in water and higher degradation tendency in the environment using DMol³ computational code. All calculations were carried out using the Becke and Perdew version of Volsko-Wilk-Nusair (VWN-BP) level of density functional theory in conjunction with double numerical basis set containing polarization function (DNP). The aqueous solubility determination was achieved with conductor-like screening model for realistic solvation (COSMO-RS) in conjunction with known empirical solubility model, while the reactivity was predicted using frontier molecular orbital calculations. Most of the new derivatives studied showed evidence of higher aqueous solubility and degradation tendency compared to the parent dye. We conclude that these derivatives are promising alternative dyes for more economic and environmental benign dyeing practice and therefore recommend them for synthesis.Keywords: aqueous solubility, azo disperse dye, degradation, disperse yellow 119, DMol³, reactivity
Procedia PDF Downloads 199757 Synthesis of New 2-(Methylthio) Benzo[g]-[1,2,4] Triazolo [1,5a] Quinazolines
Authors: Rashad A. Al-Salahi, Mohamed S. Marzouk
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Aiming to the synthesis of bioactive triazoloquinazolines, a new series of 2-(methylthio)benzo [g]-[1,2,4] triazolo [1,5-a] quinazolin-5(4H)-ones was synthesized from 2-(methylthio)benzo [g]-[1,2,4] triazolo [1,5-a] quinazolin-5(4H)-one. All synthesized derivatives based on N-alkylation and chlorination of the parent compound and its salfonyl derivative. The success of the reactions was proved by NMR, IR, and HREI-MS analyses for all products.Keywords: triazoloquinazoline, alkylation, thionation, quinazolin
Procedia PDF Downloads 355756 Catalytic Synthesis and Characterization of N-(4-(Tert-Butyl) Benzyl)-1-(4-Tert-Butyl) Phenyl)-N-Methyl Methanaminium Chloride from Tert-Butyl Benzyl Derivatives
Authors: Muhammad A. Muhammad
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Butenafine (N-4-tert-butyl benzyl-N-methyl-1-naphthylene methylamine hydrochloride) is a benzylamine antimycotic (antifungal) agent that has a broad spectrum of action. The quest for improved antimycotic action brought about many research on the structure-activity properties of butenafine in relation to other antifungal agents. Of all those research, only little or no effort was recorded on the substituents attached to the aromatic systems in butenafine. In this research, N-(4-(tert-butyl) benzyl)-1-(4-tert-butyl) phenyl)-N-methyl methanaminium chloride, which is a butenafine analogue was synthesised from tert-butyl benzyl derivatives, by reductive amination using various solvents through a direct approach, where 1,2-dichloroethane gave the best solvent action at 40 °C (Yield: 75%) and of all the reducing agents used, sodium borohydride was found to give the best reducing action in the presence of silica chloride at room temperature (Yield: 50%). Characterization of the compound by 1H NMR showed a singlet peak of 18 hydrogen atoms with a chemical shift at 1.3-1.5 ppm for the presence of 6 methyl groups in the two tert-butyl substituents, the 13C NMR also indicated the presence of the two tert-butyl substituents by the peak with a chemical shift at 31-32 ppm for the six methyl carbon atoms, the IR indicated the presence of a tertiary ammonium ion by a strong band at 2460 cm-1 and finally the EIS-MS confirmed the molar mass of the compound by a mass to charge ratio of 324.2693. These results suggested that the target molecule was actually synthesised and therefore, 1,2-dichloroethane is a good solvent for this synthesis, and the most suitable reducing agent is sodium borohydride.Keywords: antimicrobial agents, antimycotic agents, butenafine, chemotherapeutic agents, semisynthetic agents
Procedia PDF Downloads 290755 Optimal Image Representation for Linear Canonical Transform Multiplexing
Authors: Navdeep Goel, Salvador Gabarda
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Digital images are widely used in computer applications. To store or transmit the uncompressed images requires considerable storage capacity and transmission bandwidth. Image compression is a means to perform transmission or storage of visual data in the most economical way. This paper explains about how images can be encoded to be transmitted in a multiplexing time-frequency domain channel. Multiplexing involves packing signals together whose representations are compact in the working domain. In order to optimize transmission resources each 4x4 pixel block of the image is transformed by a suitable polynomial approximation, into a minimal number of coefficients. Less than 4*4 coefficients in one block spares a significant amount of transmitted information, but some information is lost. Different approximations for image transformation have been evaluated as polynomial representation (Vandermonde matrix), least squares + gradient descent, 1-D Chebyshev polynomials, 2-D Chebyshev polynomials or singular value decomposition (SVD). Results have been compared in terms of nominal compression rate (NCR), compression ratio (CR) and peak signal-to-noise ratio (PSNR) in order to minimize the error function defined as the difference between the original pixel gray levels and the approximated polynomial output. Polynomial coefficients have been later encoded and handled for generating chirps in a target rate of about two chirps per 4*4 pixel block and then submitted to a transmission multiplexing operation in the time-frequency domain.Keywords: chirp signals, image multiplexing, image transformation, linear canonical transform, polynomial approximation
Procedia PDF Downloads 408754 Magnetic and Optical Properties of Quaternary GaFeMnN
Authors: B. Bouadjemi, S. Bentata, A. Abbad, W.Benstaali
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The full-potential linearized augmented plane wave method (FP-LAPW) within the Generalized Gradient Approximation (GGA) is used to calculate the magnetic and optical properties of quaternary GaFeMnN. The results show that the compound becomes magnetic and half metallic and there is an apparition of peaks at low frequencies for the optical properties.Keywords: optical properties, DFT, Spintronic, wave
Procedia PDF Downloads 544753 Technologies of Isolation and Separation of Anthraquinone Derivatives
Authors: Dmitry Yu. Korulkin, Raissa A. Muzychkina
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In review the generalized data about different methods of extraction, separation and purification of natural and modify anthraquinones is presented. The basic regularity of an isolation process is analyzed. Action of temperature, pH, and polarity of extragent, catalysts and other factors on an isolation process is revealed. Procedia PDF Downloads 333752 Theoretical Analysis of the Existing Sheet Thickness in the Calendering of Pseudoplastic Material
Authors: Muhammad Zahid
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The mechanical process of smoothing and compressing a molten material by passing it through a number of pairs of heated rolls in order to produce a sheet of desired thickness is called calendering. The rolls that are in combination are called calenders, a term derived from kylindros the Greek word for the cylinder. It infects the finishing process used on cloth, paper, textiles, leather cloth, or plastic film and so on. It is a mechanism which is used to strengthen surface properties, minimize sheet thickness, and yield special effects such as a glaze or polish. It has a wide variety of applications in industries in the manufacturing of textile fabrics, coated fabrics, and plastic sheeting to provide the desired surface finish and texture. An analysis has been presented for the calendering of Pseudoplastic material. The lubrication approximation theory (LAT) has been used to simplify the equations of motion. For the investigation of the nature of the steady solutions that exist, we make use of the combination of exact solution and numerical methods. The expressions for the velocity profile, rate of volumetric flow and pressure gradient are found in the form of exact solutions. Furthermore, the quantities of interest by engineering point of view, such as pressure distribution, roll-separating force, and power transmitted to the fluid by the rolls are also computed. Some results are shown graphically while others are given in the tabulated form. It is found that the non-Newtonian parameter and Reynolds number serve as the controlling parameters for the calendering process.Keywords: calendering, exact solutions, lubrication approximation theory, numerical solutions, pseudoplastic material
Procedia PDF Downloads 138751 The Empirical Analysis and Comparisons Using TAIEX Derivatives
Authors: Pao-Peng Hsu, Ying-Hsiu Chen
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Historical data shows that there were high correlations among TAIEX Futures, Electronic Sector Index Futures, Finance Sector Index Futures and Taiwan Top 50 ETF. The performance under various futures is also discussed. We found that the worst portfolio is consisted of T50-ETF and T50-ETF futures and best portfolio is consisted of T50-ETF and TF. It implies that the annual return of a portfolio increases if a portfolio’s risk diversifies.Keywords: arbitrage opportunities, ETF, futures, TAIEX
Procedia PDF Downloads 375750 Opto-Electronic Properties and Structural Phase Transition of Filled-Tetrahedral NaZnAs
Authors: R. Khenata, T. Djied, R. Ahmed, H. Baltache, S. Bin-Omran, A. Bouhemadou
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We predict structural, phase transition as well as opto-electronic properties of the filled-tetrahedral (Nowotny-Juza) NaZnAs compound in this study. Calculations are carried out by employing the full potential (FP) linearized augmented plane wave (LAPW) plus local orbitals (lo) scheme developed within the structure of density functional theory (DFT). Exchange-correlation energy/potential (EXC/VXC) functional is treated using Perdew-Burke and Ernzerhof (PBE) parameterization for generalized gradient approximation (GGA). In addition to Trans-Blaha (TB) modified Becke-Johnson (mBJ) potential is incorporated to get better precision for optoelectronic properties. Geometry optimization is carried out to obtain the reliable results of the total energy as well as other structural parameters for each phase of NaZnAs compound. Order of the structural transitions as a function of pressure is found as: Cu2Sb type → β → α phase in our study. Our calculated electronic energy band structures for all structural phases at the level of PBE-GGA as well as mBJ potential point out; NaZnAs compound is a direct (Γ–Γ) band gap semiconductor material. However, as compared to PBE-GGA, mBJ potential approximation reproduces higher values of fundamental band gap. Regarding the optical properties, calculations of real and imaginary parts of the dielectric function, refractive index, reflectivity coefficient, absorption coefficient and energy loss-function spectra are performed over a photon energy ranging from 0.0 to 30.0 eV by polarizing incident radiation in parallel to both [100] and [001] crystalline directions.Keywords: NaZnAs, FP-LAPW+lo, structural properties, phase transition, electronic band-structure, optical properties
Procedia PDF Downloads 426749 Chemical Modifications of Carotol and Their Antioxidant Activity
Authors: Dalvir Kataria, Khushminder Kaur Chahal, Amit Kumar
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The carrot seed essential oil was obtained by hydrodistillation. Hexane, dichloromethane, and methanol solvents were used for extraction of carrot seed by Soxhlet extraction methods. The major and minor compounds identified in carrot seed essential oil were carotol (52.73), daucol (5.10), daucene (5.68), (E)-β-farnesene (5.40), β-cubebene (3.19), longifolenaldehyde (3.23), β-elimene (3.23), (E)-caryophyllene (1.22), β-bisabolene (2.95) etc. The chemical composition of hexane, dichloromethane, and methanol extracts was different. Carotol was the common compound present. Major compounds isolated were from the carrot seed essential oil by column chromatography. Chemical transformations of carotol (2) with mercuric acetate/sodium borohydride, dry hydrochloric acid gas, acetonitrile/sulfuric acid, selenium dioxide/t-butyl hydrogen peroxide, N-bromosuccinimide, hydrogen iodide, and phenol were carried out. The derivatives of carotol were designed to explore the significance of some structural modifications in relation to antioxidant activities. The structures of major compounds and derivatives were confirmed on the basis of FT-IR, 1HNMR and 13CNMR spectroscopy. Antioxidant activity of carrot seed essential oil, various extracts and isolated compounds were tested by in vitro models involving 2, 2-diphenyl-1-picrylhydrazyl (DPPH•), hydroxyl (OH•), nitric oxide (NO•), superoxide radical scavenging methods and ferric reducing antioxidant power assay (FRAP). Chemical transformations of major isolated compound carotol were carried out, and antioxidant activity of all compounds was undertaken. The major sesquiterpenoidcarotol isolated from carrot seed essential oil showed the highest antioxidant activity in all the methods. The methanol extract showed higher antioxidant potential as compared to carrot seed essential oil, hexane, and dichloromethane extracts.Keywords: antioxidant, carotol, carrot, DPPH
Procedia PDF Downloads 128748 Numerical Simulation of Phase Transfer during Cryosurgery for an Irregular Tumor Using Hybrid Approach
Authors: Rama Bhargava, Surabhi Nishad
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The infusion of nanofluids has dramatically enhanced the heat-carrying capacity of the fluids, applicable to many engineering and medical process where the temperature below freezing is required. Cryosurgery is an efficient therapy for the treatment of cancer, but sometimes the excessive cooling may harm the nearby healthy cells. Efforts are therefore done to develop a model which can cause to generate the low temperature as required. In the present study, a mathematical model is developed based on the bioheat transfer equation to simulate the heat transfer from the probe on a tumor (with irregular domain) using the hybrid technique consisting of element free Galerkin method with αα-family of approximation. The probe is loaded will nano-particles. The effects of different nanoparticles, namely Al₂O₃, Fe₃O₄, Au on the heat-producing rate, is obtained. It is observed that the temperature can be brought to (60°C)-(-30°C) at a faster freezing rate on the infusion of different nanoparticles. Besides increasing the freezing rate, the volume of the nanoparticle can also control the size and growth of ice crystals formed during the freezing process. The study is also made to find the time required to achieve the desired temperature. The problem is further extended for multi tumors of different shapes and sizes. The irregular shape of the frozen domain and the direction of ice growth are very sensitive issues, posing a challenge for simulation. The Meshfree method has been one of the accurate methods in such problems as a domain is naturally irregular. The discretization is done using the nodes only. MLS approximation is taken in order to generate the shape functions. Sufficiently accurate results are obtained.Keywords: cryosurgery, EFGM, hybrid, nanoparticles
Procedia PDF Downloads 115747 Exploring 1,2,4-Triazine-3(2H)-One Derivatives as Anticancer Agents for Breast Cancer: A QSAR, Molecular Docking, ADMET, and Molecular Dynamics
Authors: Said Belaaouad
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This study aimed to explore the quantitative structure-activity relationship (QSAR) of 1,2,4-Triazine-3(2H)-one derivative as a potential anticancer agent against breast cancer. The electronic descriptors were obtained using the Density Functional Theory (DFT) method, and a multiple linear regression techniques was employed to construct the QSAR model. The model exhibited favorable statistical parameters, including R2=0.849, R2adj=0.656, MSE=0.056, R2test=0.710, and Q2cv=0.542, indicating its reliability. Among the descriptors analyzed, absolute electronegativity (χ), total energy (TE), number of hydrogen bond donors (NHD), water solubility (LogS), and shape coefficient (I) were identified as influential factors. Furthermore, leveraging the validated QSAR model, new derivatives of 1,2,4-Triazine-3(2H)-one were designed, and their activity and pharmacokinetic properties were estimated. Subsequently, molecular docking (MD) and molecular dynamics (MD) simulations were employed to assess the binding affinity of the designed molecules. The Tubulin colchicine binding site, which plays a crucial role in cancer treatment, was chosen as the target protein. Through the simulation trajectory spanning 100 ns, the binding affinity was calculated using the MMPBSA script. As a result, fourteen novel Tubulin-colchicine inhibitors with promising pharmacokinetic characteristics were identified. Overall, this study provides valuable insights into the QSAR of 1,2,4-Triazine-3(2H)-one derivative as potential anticancer agent, along with the design of new compounds and their assessment through molecular docking and dynamics simulations targeting the Tubulin-colchicine binding site.Keywords: QSAR, molecular docking, ADMET, 1, 2, 4-triazin-3(2H)-ones, breast cancer, anticancer, molecular dynamic simulations, MMPBSA calculation
Procedia PDF Downloads 83746 Design of Two-Channel Quadrature Mirror Filter Banks Using a Transformation Approach
Authors: Ju-Hong Lee, Yi-Lin Shieh
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Two-dimensional (2-D) quadrature mirror filter (QMF) banks have been widely considered for high-quality coding of image and video data at low bit rates. Without implementing subband coding, a 2-D QMF bank is required to have an exactly linear-phase response without magnitude distortion, i.e., the perfect reconstruction (PR) characteristics. The design problem of 2-D QMF banks with the PR characteristics has been considered in the literature for many years. This paper presents a transformation approach for designing 2-D two-channel QMF banks. Under a suitable one-dimensional (1-D) to two-dimensional (2-D) transformation with a specified decimation/interpolation matrix, the analysis and synthesis filters of the QMF bank are composed of 1-D causal and stable digital allpass filters (DAFs) and possess the 2-D doubly complementary half-band (DC-HB) property. This facilitates the design problem of the two-channel QMF banks by finding the real coefficients of the 1-D recursive DAFs. The design problem is formulated based on the minimax phase approximation for the 1-D DAFs. A novel objective function is then derived to obtain an optimization for 1-D minimax phase approximation. As a result, the problem of minimizing the objective function can be simply solved by using the well-known weighted least-squares (WLS) algorithm in the minimax (L∞) optimal sense. The novelty of the proposed design method is that the design procedure is very simple and the designed 2-D QMF bank achieves perfect magnitude response and possesses satisfactory phase response. Simulation results show that the proposed design method provides much better design performance and much less design complexity as compared with the existing techniques.Keywords: Quincunx QMF bank, doubly complementary filter, digital allpass filter, WLS algorithm
Procedia PDF Downloads 221745 Acanthopanax koreanum and Major Ingredient, Impressic Acid, Possess Matrix Metalloproteinase-13 Down-Regulating Capacity and Protect Cartilage Destruction
Authors: Hyun Lim, Dong Sook Min, Han Eul Yun, Kil Tae Kim, Ya Nan Sun, Young Ho Kim, Hyun Pyo Kim
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Matrix metalloproteinase (MMP)-13 has an important role for degrading cartilage materials under inflammatory conditions such as arthritis. Since the 70% ethanol extract of Acanthopanax koreanum inhibited MMP-13 expression in IL-1β-treated human chondrocyte cell line, SW1353, two major constituents including acanthoic acid and impressic acid were initially isolated from the same plant materials and their MMP-13 down-regulating capacity was examined. In IL-1β-treated SW1353 cells, acanthoic acid and impressic acid significantly and concentration-dependently inhibited MMP-13 expression at 10 – 100 μM and 0.5 – 10 μM, respectively. The potent one, impressic acid, was found to inhibit MMP-13 expression by blocking the phosphorylation of signal transducer and activator of transcription-1/-2 (STAT-1/-2) and activation of c-Jun and c-Fos among cellular signaling pathway involved, but did not affect the activation of mitogen-activated protein kinases (MAPKs) and nuclear transcription factor-κB (NF-κB). Further, impressic acid was also found to inhibit the expression of MMP-13 mRNA (47.7% inhibition at 10 μM), the glycosaminoglycan release (42.2% reduction at 10 μM) and proteoglycan loss in IL-1-treated rabbit cartilage explants culture. For a further study, 21 impressic acid derivatives were isolated from the same plant materials and their suppressive activities against MMP-13 expression were examined. Among the derivatives, 3α-hydroxy-lup-20(29)-en-23-oxo,28-oic acid, (20R)-3α-hydroxy-29-dimethoxylupan-23,28-dioic acid, acankoreoside F and acantrifoside A clearly down-regulated MMP-13 expression, but impressic acid being most potent. All these results suggest that impressic acid, 3α-hydroxy-lup-20(29)-en-23-oxo,28-oic acid, (20R)-3α-hydroxy-29-dimethoxylupan-23,28-dioic acid, acankoreoside F, acantrifoside A and A. koreanum may have a potential for therapeutic agents to prevent cartilage degradation possibly by inhibiting matrix protein degradation.Keywords: acanthoic acid, Acanthopanax koreanum, cartilage, impressic acid, matrix metalloproteinase
Procedia PDF Downloads 355