Search results for: compound interest
4667 Isolation of Cytotoxic Compound from Tectona grandis Stem to Be Used as Thai Medicinal Preparation for Cancer Treatment
Authors: Onmanee Prajuabjinda, Pakakrong Thondeeying, Jipisute Chunthorng-Orn, Bhanuz Dechayont, Arunporn Itharat
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A Thai medicinal preparation has been used for cancer treatment more than ten years ago in Khampramong Temple. Tectona grandis stem is one ingredient of this Thai medicinal remedy. The ethanolic extract of Tectona grandis stem showed the highest cytotoxic activities against human breast adenocarcinoma (MCF-7), but was less cytotoxic against large cell lung carcinoma (COR-L23) (IC50 = 3.92 and 7.78 µg/ml, respectively). It was isolated by bioassay-guided isolation method. Tectoquinone, a anthraquinone compound was isolated from this plant. This compound showed high specific cytotoxicity against human breast adenocarcinoma (MCF-7), but was less cytotoxic against large cell lung carcinoma (COR-L23)(IC50 =16.15 and 47.56 µg/ml or 72.67 and 214.00 µM, respectively). However, it showed less cytotoxic activity than the crude extract. In conclusion, tectoquinone as a main compound, is not the best cytotoxic compound from Tectona grandis, so there are more active cytotoxic compounds in this extract which should be isolated in the future. Moreover, tectoquinone displayed specific cytotoxicity against only human breast adenocarcinoma (MCF-7) which is a good criterion for cancer treatment.Keywords: Tectona grandis, SRB assay, cytotoxicity, tectoquinone
Procedia PDF Downloads 4054666 Computational Determination of the Magneto Electronic Properties of Ce₁₋ₓCuₓO₂ (x=12.5%): Emerging Material for Spintronic Devices
Authors: Aicha Bouhlala, Sabah Chettibi
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Doping CeO₂ with transition metals is an effective way of tuning its properties. In the present work, we have performed self-consistent ab-initio calculation using the full-potential linearized augmented plane-wave method (FP-LAPW), based on the density functional theory (DFT) as implemented in the Wien2k simulation code to study the structural, electronic, and magnetic properties of the compound Ce₁₋ₓCuₓO₂ (x=12.5%) fluorite type oxide and to explore the effects of dopant Cu in ceria. The exchange correlation potential has been treated using the Perdew-Burke-Eenzerhof revised of solid (PBEsol). In structural properties, the equilibrium lattice constant is observed for the compound, which exists within the value of 5.382 A°. In electronic properties, the spin-polarized electronic bandstructure elucidates the semiconductor nature of the material in both spin channels, with the compound was observed to have a narrow bandgap on the spin-down configuration (0.162 EV) and bandgap on the spin-up (2.067 EV). Hence, the doped atom Cu plays a vital role in increasing the magnetic moments of the supercell, and the value of the total magnetic moment is found to be 2.99438 μB. Therefore, the compound Cu-doped CeO₂ shows a strong ferromagnetic behavior. The predicted results propose the compound could be a good candidate for spintronics applications.Keywords: Cu-doped CeO₂, DFT, Wien2k, properties
Procedia PDF Downloads 2224665 Evaluation of Cytotoxic Effect of Two Diterpenes from Plectranthus barbatus
Authors: Nawal Al Musayeib, Musarat Amina, Perwez Alam
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Plectranthus barbatus Andrews (Lamiaceae) is the most common species of genus Plectranthus. It is used for treating various ailments. In this study, two rare diterpenes 11,14-dihydroxy-8,11,13-abietatrien-7-one (1) and 12-hydroxyabieta-8(14),9(11),12-trien-7-one (2) were isolated for the first time from P. barbatus. Their chemical structures were verified utilizing various spectroscopic experiments. The effect of diterpenes against undifferentiated/anaplastic thyroid cancer cell line (FRO) was evaluated and they were quantitatively analysed using HPTLC method. The two diterpenes were found to be cytotoxic, however compound 1 showed significant cytotoxic effects where 95% reduction in the cell viability was observed in different time intervals. The quantity of compound 1 and compound 2 in PBCE were found to be 2.04 and15.97 μg/mg, respectively of dried weight of the extract.Keywords: abietatrien, cancer, diterpenes, Plectranthus barbatus
Procedia PDF Downloads 2204664 Explicable Enzymatic Mechanism of H-Ido to Oxidise Tryptophan by Employing Various Substrates
Authors: Ali Bahri Lubis
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The study of dioxygenase enzymatic mechanism on tryptophan oxidation has been a wide interest since the reaction is rate-limiting step of kynurenine pathway. In this research, observation of tryptophan oxidation through h-IDO enzyme along with synthesis of enzyme products was conducted in order to comprehend how the enzyme works on distinct substrates. UV-vis spectrophotometry, LC-MS, H-NMR and HSQC measurement were carried out to characterise enzyme product. It is found that while tryptophan was oxidised to form Nformylkynurenine (NFK) as a major product and hydroxypyrroloindole amine carboxylic acid (HPIC) in cis and trans confirmed in HSQC, N-methyl tryptophan substrate was converted to NFK and trans HPIC only. Other intriguing results showed that 5-hydroxy- tryptophan and Stryptophan was degraded to become NFK and epoxide cyclic respectively. The formation of NFK was considered through dioxygenation pathway, however HPIC was formed via monooxygenation. The epoxide cyclic—considered as intermediate compound in the mechanism— from S-tryptophan was not able to cleave the epoxide ring since bond energy of epoxide was probably much stronger. This validates the enzymatic mechanism where the intermediate compound in the enzymatic mechanism is epoxide cyclic.Keywords: tryptophan oxidation, heme-dioxygenases, N-formylkynurenine, hydroxypyrrroloindoleamine, monooxidation
Procedia PDF Downloads 564663 A Hyperexponential Approximation to Finite-Time and Infinite-Time Ruin Probabilities of Compound Poisson Processes
Authors: Amir T. Payandeh Najafabadi
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This article considers the problem of evaluating infinite-time (or finite-time) ruin probability under a given compound Poisson surplus process by approximating the claim size distribution by a finite mixture exponential, say Hyperexponential, distribution. It restates the infinite-time (or finite-time) ruin probability as a solvable ordinary differential equation (or a partial differential equation). Application of our findings has been given through a simulation study.Keywords: ruin probability, compound poisson processes, mixture exponential (hyperexponential) distribution, heavy-tailed distributions
Procedia PDF Downloads 3154662 Computational Analysis of Potential Inhibitors Selected Based on Structural Similarity for the Src SH2 Domain
Authors: W. P. Hu, J. V. Kumar, Jeffrey J. P. Tsai
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The inhibition of SH2 domain regulated protein-protein interactions is an attractive target for developing an effective chemotherapeutic approach in the treatment of disease. Molecular simulation is a useful tool for developing new drugs and for studying molecular recognition. In this study, we searched potential drug compounds for the inhibition of SH2 domain by performing structural similarity search in PubChem Compound Database. A total of 37 compounds were screened from the database, and then we used the LibDock docking program to evaluate the inhibition effect. The best three compounds (AP22408, CID 71463546 and CID 9917321) were chosen for MD simulations after the LibDock docking. Our results show that the compound CID 9917321 can produce a more stable protein-ligand complex compared to other two currently known inhibitors of Src SH2 domain. The compound CID 9917321 may be useful for the inhibition of SH2 domain based on these computational results. Subsequently experiments are needed to verify the effect of compound CID 9917321 on the SH2 domain in the future studies.Keywords: nonpeptide inhibitor, Src SH2 domain, LibDock, molecular dynamics simulation
Procedia PDF Downloads 2444661 The Effect of Olea europea L. Extract on Doxorubicin-Induced Cardiotoxicity
Authors: Jessica Maiuolo, Irene Bava, Micaela Gliozzi, Vincenzo Mollace
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Doxorubicin is an anthracycline that is commonly used as a chemotherapy drug due to its cytotoxic effects. The clinical use of doxorubicin is limited due to its known cardiotoxic effects. Polyphenols have a wide range of beneficial properties, and particular importance is given to Oleuropein, one of the main polyphenolic compounds of olive oil. The biological mechanisms involved and the role of the endoplasmic reticulum were examined. Olive oil extract and Oleuropein were able to decrease the damage induced by exposure to doxorubicin. In particular, this natural compound was found to reduce cell mortality and oxidative damage, increase lipid content, and decrease the concentration of calcium ions that escaped from the endoplasmic reticulum. In addition, the direct involvement of this cellular organelle was demonstrated by silencing the ATF6 arm of the Unfolded Protein Response, which was activated after treatment with doxorubicin. The protection afforded by pre-treatment with the natural compound of interest, following the early damage induced by DOXO, provided valuable information regarding the potential use of these substances along with chemotherapy treatment.Keywords: Olea europea L., oleuropein, doxorubicin, endoplasmic reticulum, nutraceutical support
Procedia PDF Downloads 854660 Identification of Target Receptor Compound 10,11-Dihidroerisodin as an Anti-Cancer Candidate
Authors: Srie Rezeki Nur Endah, Richa Mardianingrum
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Cancer is one of the most feared diseases and is considered the leading cause of death worldwide. Generally, cancer drugs are synthetic drugs with relatively more expensive prices and have harmful side effects, so many people turn to traditional medicine, for example by utilizing herbal medicine. Erythrina poeppigiana is one of the plants that can be used as a medicinal plant containing 10,11-dihidroerisodin compounds that are useful anticancer etnofarmakologi. The purpose of this study was to identify the target of 10,11 dihydroerisodin receptor compound as in silico anticancer candidate. The pure isolate was tested physicochemically by MS (Mass Spectrometry), UV-Vis (Ultraviolet – Visible), IR (Infra Red), 13C-NMR (Carbon-13 Nuclear Magnetic Resonance), 1H-NMR (Hydrogen-1 Nuclear Magnetic Resonance), to obtain the structure of 10,11-dihydroerisodin alkaloid compound then identified to target receptors in silico. From the results of the study, it was found that 10,11-dihydroerisodin compound can work on the Serine / threonine-protein kinase Chk1 receptor that serves as an anti-cancer candidate.Keywords: anti-cancer, Erythrina poeppigiana, target receptor, 10, 11- dihidroerisodin
Procedia PDF Downloads 2284659 Medical Image Compression Based on Region of Interest: A Review
Authors: Sudeepti Dayal, Neelesh Gupta
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In terms of transmission, bigger the size of any image, longer the time the channel takes for transmission. It is understood that the bandwidth of the channel is fixed. Therefore, if the size of an image is reduced, a larger number of data or images can be transmitted over the channel. Compression is the technique used to reduce the size of an image. In terms of storage, compression reduces the file size which it occupies on the disk. Any image is based on two parameters, region of interest and non-region of interest. There are several algorithms of compression that compress the data more economically. In this paper we have reviewed region of interest and non-region of interest based compression techniques and the algorithms which compress the image most efficiently.Keywords: compression ratio, region of interest, DCT, DWT
Procedia PDF Downloads 3544658 Discovery of New Inhibitors for Colorectal Cancer Treatment
Authors: Kai-Cheng Hsu, Tzu-Ying Sung, Jinn-Moon Yang
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Colorectal cancer (CRC) is one of the main causes of cancer death in the world. Although several drugs have been developed to treat colorectal cancer, such as Regorafenib and 5-FU, their efficacy is often limited by the development of drug resistance. Therefore, development of new drugs with new scaffolds is necessary to treat CRC. Here, we used site-moiety maps to identify inhibitors against PIM1, LIMK1, SRC, and mTOR, which are often overexpressed in CRC. A site-moiety map represents physicochemical properties and moiety preferences of a binding site through anchors. An anchor contains three elements: (1) conserved interacting residues of a binding pocket; (2) moiety preference of the binding pocket; and (3) the type (e.g., hydrogen-bonding or van der Waals interactions) of interaction between the moieties and the binding pocket. Then, we performed a structure-based virtual screening of ~260,000 compounds and selected compound candidates with high site-moiety map scores for bioassays. Among these candidates, compound 1 and compound 2 inhibited the growth of CRC cells with IC50 values of <10 μM. The experimental result of enzyme-based assays indicated that compound 1 is a dual inhibitor against PIM1 (IC50 6 μM) and LIMK1(IC50 11 μM). Compound 2 was predicted as a SRC inhibitor and will be further validated. The compounds inhibited different protein targets compared to the current drugs. We believe that the compounds provide a starting point to design new drugs for CRC treatment.Keywords: colorectal cancer, drug discovery, site-moiety map, virtual screening, PIM1, LIMK1
Procedia PDF Downloads 2184657 Design, Synthesis, and Evaluation of Small Peptides for Managing Inflammation: Inhibition to Substrate Approach
Authors: Palwinder Singh, Baljit Kaur, Sukhmeet Kaur
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Amongst a library of rationally designed small peptides, (H)Gly-Gly-Phe-Leu(OMe) was identified, reducing prostaglandin production of COX-2 with IC50 60 nM vs. 6000 nM for COX-1. The 5 mg Kg-1 dose of this compound rescued albino mice by 80% from capsaicin-induced paw licking and recovered it by 60% from carrageenan-induced inflammation. The mode of action of the compound for targeting COX-2, iNOS, and VGSC was investigated by using substances P, L-arginine, and veratrine, respectively, as the biomarkers. The interactions of the potent compound with COX-2 were supported by the isothermal calorimetry experiments showing Ka 6.10±1.10x104 mol-1 and ΔG -100.3 k J mol-1 in comparison to Ka 0.41x103 ±0.09 mol-1 and ΔG -19.2±0.06 k J mol-1 for COX-1. This compound did not show toxicity up to 2000 mg Kg-1 dose. Furthermore, beyond the conventional mode of working with anti-inflammatory agents through enzyme inhibition, COX-2 was provided with a peptide-based alternate substrate. Proline-centered pentapeptide iso-conformational to arachidonic acid exhibited appreciable selectivity for COX-2 overcoming acetic acid and formalin-induced pain in rats to almost 80% and was treated as a substrate by the enzyme. Hence, we suggest small peptides as highly potent and promising candidates for their further development into an anti-inflammatory drug.Keywords: small peptides, cyclooxygenase, inflammation, substrate
Procedia PDF Downloads 594656 Interest Charges and Sustainability Challenges: The Case of OECD Countries
Authors: Aime Philombe Zapji Ymele
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Servicing public debt is a significant budgetary burden. In the sense that the payment of interest charges is a liability on the balance sheet of the public budget and affects fiscal policy. Interest charges can sometimes become a burden if they crowd out private activities. In order to analyse and understand the determinants of the debt burden and its impact on the sustainability of public finances, the present work focuses on OECD countries. It is noted from the literature that the factors that determine interest charges are macroeconomic (inflation, GDP growth, and interest rates) and public finances (primary balance and public debt). After analysing a panel of 33 OECD countries and using ordinary least squares (OLS), we find that public debt, inflation, and long-term interest rates are positively correlated with interest charges. An increase in any of these variables leads to an increase in debt charges. On the other hand, a growth in GDP is negatively associated with interest charges. Indeed, an increase in GDP generates enough revenue to meet the repayment of debt charges. According to the empirical analysis, we can say that, despite the large and growing debt-to-GDP ratio of major OECD countries, interest charges are not a threat to the sustainability of public finances. However, it is important for these countries to reduce the ratio of public debt to GDP because, in the face of the many challenges (health, aging population, etc.) that are looming on the horizon, an increase in interest rates could bring with it considerable burdens that would threaten the budgetary balance of these states.Keywords: interest charges, sustainability, public debt, interest rates
Procedia PDF Downloads 1004655 The Investigation of the Impact of Process and Location Parameters in Warpage Study of Semiconductor Packages
Authors: Wheyming Song, Ssu-Ping Lin
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The primary advantage of package-on-package (PoP) packaging is that since it has less volume, it weighs less. But this is also related to its principal drawback, which is warpage. This research investigates how PoP package warpage patterns are affected by assembling process parameters, including substrate temperature, injection speed, injection temperature, and compound forces. We also investigate how warpage patterns are affected by the location of the silicon chip. The methodologies used in this research are design of experiment and warpage simulation via ANSYS. We propose a regression model to predict the warpage value as a function of substrate temperature, injection speed, injection temperature, and compound forces. Our results show that interaction effects exist between substrate temperature and compound forces and between injection speed and injection temperature. Therefore, determining the optimal values for substrate temperature, compound forces, injection speed, and injection temperature cannot be done individually. Also, our results show that the warpage patterns based on the location of silicon chips can be classified into 11 groups, with the largest warpage occurring at the left-most and right-most sides.Keywords: package-on-package, warpage, design of experiment, simulation
Procedia PDF Downloads 2784654 X-Ray and DFT Electrostatics Parameters Determination of a Coumarin Derivative Compound C17H13NO3
Authors: Y. Megrous, A. Chouaih, F. Hamzaoui
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The crystal structure of 4-Methyl-7-(salicylideneamino)coumarin C17H13NO3has been determined using X-ray diffraction to establish the configuration and stereochemistry of the molecule. This crystal is characterized by its nolinear activity. The molecular electron charge density distribution of the title compound is described accurately using the multipolar model of Hansen and Coppens. The net atomic charge and the molecular dipole moment in-crystal have been determined in order to understand the nature of inter-and intramolecular charge transfer. The study present the thermal motion and the structural analysis obtained from the least-square refinement on F2,this study has also allowed us to determine the electrostatic potential and therefore locate the electropositive part and the electronegative part in molecular scale of the title compound.Keywords: electron charge density, net atomic charge, molecular dipole moment, X-ray diffraction
Procedia PDF Downloads 4294653 MCD-017: Potential Candidate from the Class of Nitroimidazoles to Treat Tuberculosis
Authors: Gurleen Kour, Mowkshi Khullar, B. K. Chandan, Parvinder Pal Singh, Kushalava Reddy Yumpalla, Gurunadham Munagala, Ram A. Vishwakarma, Zabeer Ahmed
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New chemotherapeutic compounds against multidrug-resistant Mycobacterium tuberculosis (Mtb) are urgently needed to combat drug resistance in tuberculosis (TB). Apart from in-vitro potency against the target, physiochemical properties and pharmacokinetic properties play an imperative role in the process of drug discovery. We have identified novel nitroimidazole derivatives with potential activity against mycobacterium tuberculosis. One lead candidates, MCD-017, which showed potent activity against H37Rv strain (MIC=0.5µg/ml) and was further evaluated in the process of drug development. Methods: Basic physicochemical parameters like solubility and lipophilicity (LogP) were evaluated. Thermodynamic solubility was determined in PBS buffer (pH 7.4) using LC/MS-MS. The partition coefficient (Log P) of the compound was determined between octanol and phosphate buffered saline (PBS at pH 7.4) at 25°C by the microscale shake flask method. The compound followed Lipinski’s rule of five, which is predictive of good oral bioavailability and was further evaluated for metabolic stability. In-vitro metabolic stability was determined in rat liver microsomes. The hepatotoxicity of the compound was also determined in HepG2 cell line. In vivo pharmacokinetic profile of the compound after oral dosing was also obtained using balb/c mice. Results: The compound exhibited favorable solubility and lipophilicity. The physical and chemical properties of the compound were made use of as the first determination of drug-like properties. The compound obeyed Lipinski’s rule of five, with molecular weight < 500, number of hydrogen bond donors (HBD) < 5 and number of hydrogen bond acceptors(HBA) not more then 10. The log P of the compound was less than 5 and therefore the compound is predictive of exhibiting good absorption and permeation. Pooled rat liver microsomes were prepared from rat liver homogenate for measuring the metabolic stability. 99% of the compound was not metabolized and remained intact. The compound did not exhibit cytoxicity in hepG2 cells upto 40 µg/ml. The compound revealed good pharmacokinetic profile at a dose of 5mg/kg administered orally with a half life (t1/2) of 1.15 hours, Cmax of 642ng/ml, clearance of 4.84 ml/min/kg and a volume of distribution of 8.05 l/kg. Conclusion : The emergence of multi drug resistance (MDR) and extensively drug resistant (XDR) Tuberculosis emphasize the requirement of novel drugs active against tuberculosis. Thus, the need to evaluate physicochemical and pharmacokinetic properties in the early stages of drug discovery is required to reduce the attrition associated with poor drug exposure. In summary, it can be concluded that MCD-017 may be considered a good candidate for further preclinical and clinical evaluations.Keywords: mycobacterium tuberculosis, pharmacokinetics, physicochemical properties, hepatotoxicity
Procedia PDF Downloads 4264652 Investigation of the Stability and Spintronic Properties of NbrhgeX (X= Cr, Co, Mn, Fe, Ni) Using Density Functional Theory
Authors: Shittu Akinpelu, Issac Popoola
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The compound NbRhGe has been predicted to be a semiconductor with excellent mechanical properties. It is an indirect band gap material. The potential of NbRhGe for non-volatile data storage via element addition is being studied using the Density Functional Theory (DFT). Preliminary results on the electronic and magnetic properties are suggestive for their application in spintronic.Keywords: half-metals, Heusler compound, semiconductor, spintronic
Procedia PDF Downloads 1364651 A Deterministic Approach for Solving the Hull and White Interest Rate Model with Jump Process
Authors: Hong-Ming Chen
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This work considers the resolution of the Hull and White interest rate model with the jump process. A deterministic process is adopted to model the random behavior of interest rate variation as deterministic perturbations, which is depending on the time t. The Brownian motion and jumps uncertainty are denoted as the integral functions piecewise constant function w(t) and point function θ(t). It shows that the interest rate function and the yield function of the Hull and White interest rate model with jump process can be obtained by solving a nonlinear semi-infinite programming problem. A relaxed cutting plane algorithm is then proposed for solving the resulting optimization problem. The method is calibrated for the U.S. treasury securities at 3-month data and is used to analyze several effects on interest rate prices, including interest rate variability, and the negative correlation between stock returns and interest rates. The numerical results illustrate that our approach essentially generates the yield functions with minimal fitting errors and small oscillation.Keywords: optimization, interest rate model, jump process, deterministic
Procedia PDF Downloads 1344650 Theoretical Investigations on Optical Properties of GaFeMnN Quaternary Compound
Authors: H. A. Bentounes, A. Abbad, W. Benstaali
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Using first principles calculations based on the density functional theory and local spin density approximation, we investigate optical properties of GaFeMnN quaternary compound. Results show that optical properties confirm that GaFeMnN can be a good candidate in the design of thin film solar cells in the visible and ultraviolet parts of the spectrum, and a good sensor in the infraredKeywords: GaN, optical absorption, semi-metallic, dielectric function
Procedia PDF Downloads 3524649 Performance of Air Cured Concrete Treated with Waterproofing Admixtures or Surface Treatments
Authors: Sirwan Kamal, Hsein Kew, Hamid Jahromi
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This paper reports results of a study conducted to investigate strength, sorptivity, and permeability under pressure of concrete specimens, cured using a water-based curing compound. The specimens are treated with waterproofing admixtures or surface treatments to enhance performance while exposed to water. Four types of concrete specimens were prepared in the laboratory, Portland cement (CEM I), Portland-fly ash (CEM II/A-V), Blast-furnace cement (CEM III) and Portland-silica fume (CEM II/A-D). Concrete cubes were de-molded three hours after casting, and sprayed with a curing compound. Admixtures were added to the mix during batching, whereas surface treatments were applied on concrete after 28 days. Compressive strength test was carried out to assess the efficiency of curing compound to develop required strength. In addition, sorptivity and permeability tests were conducted to evaluate the performance of treated specimens with respect to water ingress. Results show that strength development in specimens cured with curing compound achieved up to 96% and 90% at 7 and 28 days respectively, compared to cubes cured in water. Moreover, specimens treated with waterproofing admixtures or surface treatments materials characterized by hydrophobic impregnation considerably reduced water penetration compared to untreated control cubes. On the other hand, cubes treated with admixtures or surface treatments materials characterized by crystalline effect were ineffective in reducing water penetration.Keywords: admixtures, concrete, curing compound, surface treatments
Procedia PDF Downloads 1074648 Establishing a Drug Discovery Platform to Progress Compounds into the Clinic
Authors: Sheraz Gul
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The requirements for progressing a compound to clinical trials is well established and relies on the results from in-vitro and in-vivo animal tests to indicate that it is likely to be safe and efficacious when testing in humans. The typical data package required will include demonstrating compound safety, toxicity, bioavailability, pharmacodynamics (potential effects of the compound on body systems) and pharmacokinetics (how the compound is potentially absorbed, distributed, metabolised and eliminated after dosing in humans). If the desired criteria are met and the compound meets the clinical Candidate criteria and is deemed worthy of further development, a submission to regulatory bodies such as the US Food & Drug Administration for an exploratory Investigational New Drug Study can be made. The purpose of this study is to collect data to establish that the compound will not expose humans to unreasonable risks when used in limited, early-stage clinical studies in patients or normal volunteer subjects (Phase I). These studies are also designed to determine the metabolism and pharmacologic actions of the drug in humans, the side effects associated with increasing doses, and, if possible, to gain early evidence on their effectiveness. In order to reach the above goals, we have developed a pre-clinical high throughput Absorption, Distribution, Metabolism and Excretion–Toxicity (ADME–Toxicity) panel of assays to identify compounds that are likely to meet the Lead and Candidate compound acceptance criteria. This panel includes solubility studies in a range of biological fluids, cell viability studies in cancer and primary cell-lines, mitochondrial toxicity, off-target effects (across the kinase, protease, histone deacetylase, phosphodiesterase and GPCR protein families), CYP450 inhibition (5 different CYP450 enzymes), CYP450 induction, cardio-toxicity (hERG) and gene-toxicity. This panel of assays has been applied to multiple compound series developed in a number of projects delivering Lead and clinical Candidates and examples from these will be presented.Keywords: absorption, distribution, metabolism and excretion–toxicity , drug discovery, food and drug administration , pharmacodynamics
Procedia PDF Downloads 1534647 Effects of Concentrator and Encapsulated Phase Change Material for Desalination: An Experimental Study
Authors: Arunkumar Thirugnanasambantham, Velraj Ramalingam
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An experimental attempt has been made to study the effect of system integration by two different concentrator assisted desalting systems. The compound parabolic concentrator (CPC) and compound conical concentrator (CCC) are used in this research work. Two solar desalination systems, the single slope solar still (SSSS) and pyramid solar still (PSS), have been integrated with a CCC and compound parabolic concentrator-concentric circular tubular solar still (CPC-CCTSS). To study the effect of system integration, a thick cloth prevents the entry of sunlight into the solar still top. Additionally, the concentrator assisted desalting systems are equipped with phase change material (PCM) for enhancement. In CCC-SSSS, PCM has been filled inside copper balls and placed on the SSSS basin. The PCM is loaded in the specially designed circular trough of the tubular solar still. Here, the used concentrators and distillers are not the same. Two methodologies are followed here to produce the fresh water even while the distillers are blocked from the sunlight. They are (1) thermosyphon effect in CCC-SSSS and (2) waste heat recovery from CPC-CCTSS. The results showed that the productivity of CCC-SSSS, CCC-SSSS with PCM and CCC-SSSS (PCM) top cover shaded were found as 2680 ml / m² / day, 3240 ml / m² / day, and 1646 ml / m² / day. Similarly, the productivity of the CPC-CCTSS-PSS, CPC-CCTSS (PCM)-PSS and CPC-CCTSS (PCM)-PSS top cover shaded were found as 7160 ml / m² / day, 7346 ml / m² / day, and ml / m² / day. The productivity of the CCC-SSSS and CPC-CCTSS-PSS is examined, and conclusions are drawn such as the solar radiation blocked distillers productivity did not drop to zero.Keywords: compound conical concentrator, compound parabolic concentrator, desalination, system integration
Procedia PDF Downloads 2364646 Interest Charges and Sustainability Challenges: The Case of OECD Countries
Authors: Zapji Ymele Aime Philombe
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Servicing public debt is a significant budgetary burden in the sense that the payment of interest charges is a liability on the balance sheet of the public budget and affects fiscal policy. Interest charges can sometimes become a burden if they crowd out private activities. In order to analyse and understand the determinants of the debt burden and its impact on the sustainability of public finances, the present work focuses on OECD countries. It is noted from the literature that the factors that determine interest charges are macroeconomic (inflation, GDP growth and interest rates) and public finances (primary balance and public debt). After analysing a panel of 33 OECD countries and using ordinary least squares (OLS), we find that public debt, inflation and long-term interest rates are positively correlated with interest charges. An increase in any of these variables leads to an increase in debt charges. On the other hand, a growth in GDP is negatively associated with interest charges. Indeed, an increase in GDP generates enough revenue to meet the repayment of debt charges. According to the empirical analysis, we can say that, despite the large and growing debt-to-GDP ratio of major OECD countries, interest charges are not a threat to the sustainability of public finances. However, it is important for these countries to reduce the ratio of public debt to GDP because, in the face of the many challenges (health, aging population, etc.) that are looming on the horizon, an increase in interest rates could bring with it considerable burdens that would threaten the budgetary balance of these states.Keywords: interests charges, public debt, sustainability, interest rates
Procedia PDF Downloads 984645 Tracking of Linarin from the Ethyl Acetate Fraction of Melinjo (Gnetum gnemon L.) Seeds Using Preparative High Performance Liquid Chromatography
Authors: Asep Sukohar, Ramadhan Triyandi, Muhammad Iqbal, Sahidin, Suharyani
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Introduction: Resveratrol is a class of bioactive chemicals found in melinjo, which has a wide range of biological actions. The purpose of this study is to determine the linarin content of the melinjo fraksi by using preparative-high-performance liquid chromatography (prep-HPLC). Method: Extraction used the soxhletation method with 96% ethanol solvent. Fractionation used ethyl acetate and ethanol in a ratio of 1:1. Tracing of linarin compound used prep-HPLC with a mobile phase ratio of distilled water: methanol (55: 45, v/v). The presence of linarin was detected using a wavelength of 215 nm. Fourier Transform Infrared (FTIR) was used to identify the functional groups of compound. Result: The retention time required to elute the ethyl acetate fraction was 2.601 minutes. Compound separation identification using Fourier Transform Infrared Spectroscopy - Quest Attenuated Total Reflectance (FTIR - QATR) has a similarity value range with standards from 0 to 1000. The elution results of the ethyl acetate fraction have similar values with the standard compounds linarin (668), resveratrol (578), and catechin (455). Conclusion: Tracing for active compound in the ethyl acetate fraction of Gnetum Gnemon L. using prep-HPLC showed a strong suspicion of the presence of linarin compound.Keywords: Gnetum gnemon L., linarin, prep-HPLC, fraction ethyl acetate
Procedia PDF Downloads 634644 Schiff Bases of Isatin and Admantane-1-Carbohydrazide: Synthesis, Characterization, and Anticonvulsant Activity
Authors: Hind O. Osman, Tilal Elsaman, Bashir A. Yousef, Esraa Elhadi, Aimun A. E. Ahmed, Eyman Mohamed Eltayib, Malik Suliman Mohamed, Magdi Awadalla Mohamed
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Epilepsy is the most common neurological condition and cause of substantial morbidity and mortality. In the present study, the molecular hybridization tool was adopted to obtain six Schiff bases of isatin and adamantane-1-carbohydrazide (18–23). Then, their anticonvulsant activity was evaluated using a pentylenetetrazole- (PTZ-) induced seizure model using phenobarbitone as a positive control. Our findings showed that compounds 18–23 provided significant protection against PTZ-induced seizure, and maximum activities were associated with compound 23. Moreover, all investigated compounds increased the latency of induced convulsion and reduced the duration of epilepsy, with compound 23 being the best. Interestingly, most of the synthesized molecules showed a reduction in neurological symptoms and severity of the seizure. Molecular docking studies suggest GABA-A receptor as a potential target, and in silico ADME screening revealed that the pharmaceutical properties of compound 23 are within the specified limit. Thus, compound 23 was identified as a promising candidate that warrants further drug discovery processes.Keywords: isatin and adamantane, anticonvulsant activity, PTZ-induced seizure, molecular docking
Procedia PDF Downloads 1794643 Korean Men’s Interest in Gonzo Pornography and Use of Condoms
Authors: Chyng Sun
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This brief report examines correlations between Korean men’s interest in gonzo pornography, perceptions of pornography’s functional value, and use of condoms. The report found that, neither a higher interest in gonzo or the perception that pornography is a source of sexual information was directly related to condom utilization. However, interest in gonzo pornography interacted with pornography perceptions to predict condomless sex. The findings suggest that Korean men who 1) had higher interest in viewing gonzo pornography, and 2) had a tendency to view pornography as a source of sexual information, are more likely to have sex without condoms. That is, when viewers consider pornography to be a form of sexual education, they are more likely to use the learned pornographic script to inform their sexual behavior.Keywords: Korean, male, pornography, sexuality
Procedia PDF Downloads 1294642 Empirical Research on Rate of Return, Interest Rate and Mudarabah Deposit
Authors: Inten Meutia, Emylia Yuniarti
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The objective of this study is to analyze the effects of interest rate, the rate of return of Islamic banks on the amount of mudarabah deposits in Islamic banks. In analyzing the effect of rate of return in the Islamic banks and interest rate risk in the conventional banks, the 1-month Islamic deposit rate of return and 1 month fixed deposit interest rate of a total Islamic deposit are considered. Using data covering the period from January 2010 to Sepember 2013, the study applies the regression analysis to analyze the effect between variable and independence t-test to analyze the mean difference between rate of return and rate of interest. Regression analysis shows that rate of return have significantly negative influence on mudarabah deposits, while interest rate have negative influence but not significant. The result of independent t test shows that the interest rate is not different from the rate of return in Islamic Bank. It supports the hyphotesis that rate of return in Islamic banking mimic rate of interest in conventional bank. The results of the study have important implications on the risk management practices of the Islamic banks in Indonesia.Keywords: conventional bank, interest rate, Islamic bank, rate of return
Procedia PDF Downloads 4854641 Novel Nickel Complex Compound Reactivates the Apoptotic Network, Cell Cycle Arrest and Cytoskeletal Rearrangement in Human Colon and Breast Cancer Cells
Authors: Nima Samie, Batoul Sadat Haerian, Sekaran Muniandy, M. S. Kanthimathi
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Colon and breast cancers are categorized as the most prevalent types of cancer worldwide. Recently, the broad clinical application of metal complex compounds has led to the discovery of potential therapeutic drugs. The aim of this study was to evaluate the cytotoxic action of a selected nickel complex compound (NCC) against human colon and breast cancer cells. In this context, we determined the potency of the compound in the induction of apoptosis, cell cycle arrest, and cytoskeleton rearrangement. HT-29, WiDr, CCD-18Co, MCF-7 and Hs 190.T cell lines were used to determine the IC50 of the compound using the MTT assay. Analysis of apoptosis was carried out using immunofluorescence, acridine orange/ propidium iodide double staining, Annexin-V-FITC assay, evaluation of the translocation of NF-kB, oxygen radical antioxidant capacity, quenching of reactive oxygen species content , measurement of LDH release, caspase-3/-7, -8 and -9 assays and western blotting. The cell cycle arrest was examined using flowcytometry and gene expression was assessed using qPCR array. Results showed that our nickel complex compound displayed a potent suppressive effect on HT-29, WiDr, MCF-7 and Hs 190.T after 24 h of treatment with IC50 value of 2.02±0.54, 2.13±0.65, 3.76±015 and 3.14±0.45 µM respectively. This cytotoxic effect on normal cells was insignificant. Dipping in the mitochondrial membrane potential and increased release of cytochrome c from the mitochondria indicated induction of the intrinsic apoptosis pathway by the nickel complex compound. Activation of this pathway was further evidenced by significant activation of caspase 9 and 3/7.The nickel complex compound (NCC) was also shown activate the extrinsic pathways of apoptosis by activation of caspase-8 which is linked to the suppression of NF-kB translocation to the nucleus. Cell cycle arrest in the G1 phase and up-regulation of glutathione reductase, based on excessive ROS production were also observed. The results of this study suggest that the nickel complex compound is a potent anti-cancer agent inducing both intrinsic and extrinsic pathways as well as cell cycle arrest in colon and breast cancer cells.Keywords: nickel complex, apoptosis, cytoskeletal rearrangement, colon cancer, breast cancer
Procedia PDF Downloads 2894640 Flame Retardancy of Organophosphorus Compound on Cellulose - an Eco Friendly Concern
Authors: M. A. Hannan, N. Matthias Neisius
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Organophosphorus compound diethyloxymethyl-9-oxa-10-phosphaphenanthrene-10-oxide (DOPAC) was applied on cotton cellulose to impart eco-friendly flame retardant property to it. Here acetal linkage was introduced rather than conventionally used ester linkage to rescue from the undurability problem of flame retardant compound. Some acidic catalysts, sodium dihydrogen phosphate (NaH2PO4), ammonium dihydrogen phosphate (NH4H2PO4) and phosphoric acid (H3PO4) were successfully used to form acetal linkage between the base material and flame retardant compound. Inspiring limiting oxygen index (LOI) value of 22.4 was found after exclusive washing treatment. A good outcome of total heat of combustion (THC) 6.05 KJ/g was found possible during pyrolysis combustion flow calorimetry (PCFC) test of the treated sample. Low temperature dehydration with sufficient amount of char residue (14.89%) was experienced in case of treated sample. In addition, the temperature of peak heat release rate (TPHRR) 343.061°C supported the expected low temperature pyrolysis in condensed phase mechanism. With the consequence of pyrolysis effects, thermogravimetric analysis (TGA) also reported inspiring weight retention% of the treated samples.Keywords: acetal linkage, char residue, cotton cellulose, flame retardant, loi, low temperature pyrolysis, organophosphorus, THC, THRR
Procedia PDF Downloads 2694639 Organotin (IV) Based Complexes as Promiscuous Antibacterials: Synthesis in vitro, in Silico Pharmacokinetic, and Docking Studies
Authors: Wajid Rehman, Sirajul Haq, Bakhtiar Muhammad, Syed Fahad Hassan, Amin Badshah, Muhammad Waseem, Fazal Rahim, Obaid-Ur-Rahman Abid, Farzana Latif Ansari, Umer Rashid
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Five novel triorganotin (IV) compounds have been synthesized and characterized. The tin atom is penta-coordinated to assume trigonal-bipyramidal geometry. Using in silico derived parameters; the objective of our study is to design and synthesize promiscuous antibacterials potent enough to combat resistance. Among various synthesized organotin (IV) complexes, compound 5 was found as potent antibacterial agent against various bacterial strains. Further lead optimization of drug-like properties was evaluated through in silico predictions. Data mining and computational analysis were utilized to derive compound promiscuity phenomenon to avoid drug attrition rate in designing antibacterials. Xanthine oxidase and human glucose- 6-phosphatase were found as only true positive off-target hits by ChEMBL database and others utilizing similarity ensemble approach. Propensity towards a-3 receptor, human macrophage migration factor and thiazolidinedione were found as false positive off targets with E-value 1/4> 10^-4 for compound 1, 3, and 4. Further, displaying positive drug-drug interaction of compound 1 as uricosuric was validated by all databases and docked protein targets with sequence similarity and compositional matrix alignment via BLAST software. Promiscuity of the compound 5 was further confirmed by in silico binding to different antibacterial targets.Keywords: antibacterial activity, drug promiscuity, ADMET prediction, metallo-pharmaceutical, antimicrobial resistance
Procedia PDF Downloads 4774638 Effect of Interest-Based Debt Financing Upon Sustainable Development of Residents of Pakistan
Authors: Gul Ghutai, Nouman Khan Kakar
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Interest-Based Debt Disturbs The Financial, Social And Economic Structure Of The Country, Due To Which Sustainable Development Of The Masses Is Undermined. Such As, In Pakistan, The State’s Reliance Upon Interest-Based Debt (Both Foreign And National Levels) Affects The Socio-Economic Fabrication Of The Country, Thus Undermining The Sustainable Development Of Its Residents. The Objective Of The Study Is To Analyze The Effect Of Interest-Based Debt Financing On The Well-Being Of The Masses In Pakistan. The Question Arises Whether Interest-Based Debt Financing Undermines The Sustainable Development Of The Masses Of Pakistan Or Not. Moreover, Qualitative Research Methodology Is Pursued Towards Building A Conceptual Framework By Applying An Inductive Paradigm. It Is Expected That Interest-Based Debt, Whether Acquired From Foreign Or National Institutions By The Government Of Pakistan, Undermines The Sustainable Economic Growth Of The Country. However, The State Of Pakistan Is Under A Constitutional Obligation To Attain Sustainable Development Of Its Residents In Compliance With Islamic Shariah So That Eradication Of Interest From The Economy Of Pakistan Can Be Witnessed So That The Residents Of Pakistan Can Be Served To Attain Socio-Economic Well-Being Both Tangibly And Intangibly.Keywords: socio-economic wellbeing, residents, sustainable development, interest-based debt
Procedia PDF Downloads 95