Search results for: inverse docking

Authors: Mouna Baassi, Mohamed Moussaoui, Hatim Soufi, Sanchaita RajkhowaI, Ashwani Sharma, Subrata Sinha, Said Belaaouad

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Human Immunodeficiency Virus type 1 protease (HIV-1 PR) is one of the most challenging targets of antiretroviral therapy used in the treatment of AIDS-infected people. The performance of protease inhibitors (PIs) is limited by the development of protease mutations that can promote resistance to the treatment. The current study was carried out using statistics and bioinformatics tools. A series of thirty-three compounds with known enzymatic inhibitory activities against HIV-1 protease was used in this paper to build a mathematical model relating the structure to the biological activity. These compounds were designed by software; their descriptors were computed using various tools, such as Gaussian, Chem3D, ChemSketch and MarvinSketch. Computational methods generated the best model based on its statistical parameters. The model’s applicability domain (AD) was elaborated. Furthermore, one compound has been proposed as efficient against HIV-1 protease with comparable biological activity to the existing ones; this drug candidate was evaluated using ADMET properties and Lipinski’s rule. Molecular Docking performed on Wild Type and Mutant Type HIV-1 proteases allowed the investigation of the interaction types displayed between the proteases and the ligands, Darunavir (DRV) and the new drug (ND). Molecular dynamics simulation was also used in order to investigate the complexes’ stability, allowing a comparative study of the performance of both ligands (DRV & ND). Our study suggested that the new molecule showed comparable results to that of Darunavir and may be used for further experimental studies. Our study may also be used as a pipeline to search and design new potential inhibitors of HIV-1 proteases.

Keywords: QSAR, ADMET properties, molecular docking, molecular dynamics simulation.

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Authors: Ogunrinde Roseline Bosede

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This paper presents the development, analysis and implementation of an inverse polynomial numerical method which is well suitable for solving initial value problems in first order ordinary differential equations with applications to sample problems. We also present some basic concepts and fundamental theories which are vital to the analysis of the scheme. We analyzed the consistency, convergence, and stability properties of the scheme. Numerical experiments were carried out and the results compared with the theoretical or exact solution and the algorithm was later coded using MATLAB programming language.

Keywords: differential equations, numerical, polynomial, initial value problem, differential equation

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Authors: Rizwan H. Khan, Saima Nusrat

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Despite the fact that amyloid associated neurodegenerative diseases and non-neuropathic systemic amyloidosis have allured the research endeavors, as no curative drugs have been proclaimed up till now except for symptomatic cure. Therapeutic compounds which can diminish or disaggregate such toxic oligomers and fibrillar species have been examined and more are on its way. In the present study, we had reported an extensive biophysical, microscopic and computational study, revealing that L-3, 4-dihydroxyphenylalanine (L-Dopa) possess undeniable potency to inhibit heat induced human lysozyme (HL) amyloid fibrillation and also retain the fibril disaggregating potential. L-Dopa interferes in the amyloid fibrillogenesis process by interacting hydrophobically and also by forming hydrogen bonds with the amino acid residues found in amyloid fibril forming prone region of HL as elucidated by molecular docking results. L-Dopa also disaggregates the mature amyloid fibrils into some unorganised species. Thus, L-Dopa and related compounds can work as a promising inhibitor for the therapeutic advancement prospective against systemic amyloidosis.

Keywords: amyloids, disaggregation, human lysozyme, molecular docking

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Authors: Mthokozisi Simelane

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Background: Malaria remains a life-threatening disease in tropical regions despite the advances in the treatment of this disease, it still remains a significant burden as some parasites have become resistant to the currently available drugs. This has created a necessity for the development of alternative, more efficient antimalarial drugs. Warburgia salutaris is a traditional medicinal plant used in malaria treatment by Zulu traditional healers. Materials and methods: The W. salutaris stem-bark was extracted with dichloromethane and the compound was isolated through column chromatography. The compound was identified and characterized by spectroscopic analysis (1H NMR, 13C NMR, IR and MS) and the structure was also confirmed by x-ray crystallography. The anti-plasmodial activity (in vitro) was studied on NF54 Plasmodium falciparum strain (CQS). Cytotoxicity was measured using the MTT assay on HEK239 and HEPG2 cell lines. Docking of Mukaadial acetate was conducted in AutoDock Vina. Structural modifications were conducted in UCSF Chimera and molecular interactions examined in LigPlot. Results: The compound, Mukaadial Acetate showed appreciable inhibition (IC50 0.44±0.10 µg/ml) of the parasite growth and cytotoxicity activity of 0.124±0.109 and 0.199±0.083 (µg/ml) on HEK293 and HEPG2 cells respectively. Molecular docking revealed that Mukaadial Acetate binds to the purine, pyrophosphate and ribose binding sites of the PfHGXPRT with an optimum binding conformation and forms hydrogen bond, steric and hydrophobic interactions with the residues inhabiting the respective binding sites. Conclusion: It is apparent that W. salutaris contains components (including Mukaadial Acetate) that exhibit antimalarial activity. This study scientifically validates the use of this plant in folk medicine.

Keywords: plasmodium falciparum, molecular docking, antimalarial activity, PfHGXPRT, Warburgia salutaris, mukaadial acetate

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Authors: Mor Diama L. O., Matthieu Davy, Laurent Ferro-Famil

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In this article, inverse synthetic aperture radar (ISAR) is combined with compressive imaging techniques in order to perform 3D interferometric imaging. Interferometric ISAR (InISAR) imaging relies on a two-dimensional antenna array providing diversities in the elevation and azimuth directions. However, the signals measured over several antennas must be acquired by coherent receivers resulting in costly and complex hardware. This paper proposes to use a chaotic cavity as a compressive device to encode the signals arising from several antennas into a single output port. These signals are then reconstructed by solving an inverse problem. Our approach is demonstrated experimentally with a 3-elements L-shape array connected to a metallic compressive enclosure. The interferometric phases estimated from a unique broadband signal are used to jointly estimate the target’s effective rotation rate and the height of the dominant scattering centers of our target. Our experimental results show that the use of the compressive device does not adversely affect the performance of our imaging process. This study opens new perspectives to reduce the hardware complexity of high-resolution ISAR systems.

Keywords: interferometric imaging, inverse synthetic aperture radar, compressive device, computational imaging

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Authors: Sema Şenoğlu, Sevgi Karakuş

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Hydrazone scaffold is important to design new drug groups and is found to possess numerous uses in pharmaceutical chemistry. Besides, hydrazone derivatives are also known for biological activities such as anticancer, antimicrobial, antiviral, and antifungal. Hydrazone derivatives are promising anticancer agents because they inhibit cancer proliferation and induce apoptosis. Human carbonic anhydrase IX has a high potential to be an antiproliferative drug target, and targeting this protein is also important for obtaining potential anticancer inhibitors. The protein construct was retrieved as a PDB file from the RCSB protein database. This binding interaction of proteins and ligands was performed using Discovery Studio Visualizer. In vitro inhibitory activity of hydrazone derivatives was tested against enzyme carbonic anhydrase IX on the PyRx programme. Most of these molecules showed remarkable human carbonic anhydrase IX inhibitory activity compared to the acetazolamide. As a result, these compounds appear to be a potential target in drug design against human carbonic anhydrase IX.

Keywords: cancer, carbonic anhydrase IX enzyme, docking, hydrazone

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Authors: F. Ambreen, A.Naheed

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Osteoarthritis (OA) is a degenerative disorder affecting millions of people worldwide. Nitric oxide (NO) was found to play a catabolic role in the development of osteoarthritis. It is a toxic free radical gas generated during the metabolism of L-arginine by the enzyme Nitric oxide synthase (NOS). Inducible Nitric Oxide Synthase (iNOS) is one of the isoform of NOS, and its overexpression leads to the excessive formation of NO that results in pathophysiological joint conditions. Several synthetic anti-inflammatory drugs and inhibitors are present to date, but all showed side effects and complications. Therefore, the pursuit of natural disease-modifying drugs remains a top priority. Curcumin is an active component of turmeric, and the past few decades have witnessed intense research devoted to the antioxidant and anti-inflammatory properties of curcumin. The present study focused on curcumin and its derivatives in the search for new iNOS inhibitors for the treatment of osteoarthritis. We conducted a molecular docking study on curcumin and its four derivatives; cyclocurcumin, tetrahydrocurcumin, demethoxycurcumin and curcumin monoglucoside with iNOS using CLC Drug discovery work bench 3.02. We selected two co-crystallized ligands for this study; tetrahydrobiopterin and N-omega-propyl-L-arginine present in complex with the enzyme iNOS. Results showed the best binding affinity of N-omega-propyl-L-arginine with cyclocurcumin and curcumin monoglucoside that exhibit binding energies of -65.2 kcal/mol and -68 kcal/mol respectively. Whereas with tetrahydrobiopterin, best binding scores of -64.7 kcal/mol and -62.2 kcal/mol were found with tetrahydrocurcumin and demethoxycurcumin respectively. This information could open doors of research for the designing of novel drugs using herbs such as curcumin for the treatment of inflammatory joint diseases.

Keywords: curcumin, iNOS, molecular docking, osteoarthritis

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Authors: Adnan A. Y. Mustafa

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Image matching is a fundamental problem that arises frequently in many aspects of robot and computer vision. It can become a time-consuming process when matching images to a database consisting of hundreds of images, especially if the images are big. One approach to reducing the time complexity of the matching process is to reduce the search space in a pre-matching stage, by simply removing dissimilar images quickly. The Probabilistic Matching Model for Binary Images (PMMBI) showed that dissimilarity detection between binary images can be accomplished quickly by random pixel mapping and is size invariant. The model is based on the gamma binary similarity distance that recognizes an image and its inverse as containing the same scene and hence considers them to be the same image. However, in many applications, an image and its inverse are not treated as being the same but rather dissimilar. In this paper, we present a comparative analysis of dissimilarity detection between PMMBI based on the gamma binary similarity distance and a modified PMMBI model based on a similarity distance that does distinguish between an image and its inverse as being dissimilar.

Keywords: binary image, dissimilarity detection, probabilistic matching model for binary images, image mapping

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Authors: Fatemah A. Alqallaf, Debasis Kundu

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The aim of this paper is to introduce a bivariate inverse generalized exponential distribution which has a singular component. The proposed bivariate distribution can be used when the marginals have heavy-tailed distributions, and they have non-monotone hazard functions. Due to the presence of the singular component, it can be used quite effectively when there are ties in the data. Since it has four parameters, it is a very flexible bivariate distribution, and it can be used quite effectively for analyzing various bivariate data sets. Several dependency properties and dependency measures have been obtained. The maximum likelihood estimators cannot be obtained in closed form, and it involves solving a four-dimensional optimization problem. To avoid that, we have proposed to use an EM algorithm, and it involves solving only one non-linear equation at each `E'-step. Hence, the implementation of the proposed EM algorithm is very straight forward in practice. Extensive simulation experiments and the analysis of one data set have been performed. We have observed that the proposed bivariate inverse generalized exponential distribution can be used for modeling dependent competing risks data. One data set has been analyzed to show the effectiveness of the proposed model.

Keywords: Block and Basu bivariate distributions, competing risks, EM algorithm, Marshall-Olkin bivariate exponential distribution, maximum likelihood estimators

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Authors: Zohreh Moghaddas, Morteza Yazdani, Farhad Hosseinzadeh

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Nowadays, data envelopment analysis (DEA) models featuring network structures have gained widespread usage for evaluating the performance of production systems and activities (Decision-Making Units (DMUs)) across diverse fields. By examining the relationships between the internal stages of the network, these models offer valuable insights to managers and decision-makers regarding the performance of each stage and its impact on the overall network. To further empower system decision-makers, the inverse data envelopment analysis (IDEA) model has been introduced. This model allows the estimation of crucial information for estimating parameters while keeping the efficiency score unchanged or improved, enabling analysis of the sensitivity of system inputs or outputs according to managers' preferences. This empowers managers to apply their preferences and policies on resources, such as inputs and outputs, and analyze various aspects like production, resource allocation processes, and resource efficiency enhancement within the system. The results obtained can be instrumental in making informed decisions in the future. The top result of this study is an analysis of infeasibility and incorrect estimation that may arise in the theory and application of the inverse model of data envelopment analysis with network structures. By addressing these pitfalls, novel protocols are proposed to circumvent these shortcomings effectively. Subsequently, several theoretical and applied problems are examined and resolved through insightful case studies.

Keywords: inverse models of data envelopment analysis, series network, estimation of inputs and outputs, efficiency, resource allocation, sensitivity analysis, infeasibility

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Authors: Mohamed Moussaoui

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A series of thirty-one potential inhibitors targeting the epidermal growth factor receptor kinase (EGFR), derived from quinazoline, underwent 3D-QSAR analysis using CoMFA and CoMSIA methodologies. The training and test sets of quinazoline derivatives were utilized to construct and validate the QSAR models, respectively, with dataset alignment performed using the lowest energy conformer of the most active compound. The best-performing CoMFA and CoMSIA models demonstrated impressive determination coefficients, with R² values of 0.981 and 0.978, respectively, and Leave One Out cross-validation determination coefficients, Q², of 0.645 and 0.729, respectively. Furthermore, external validation using a test set of five compounds yielded predicted determination coefficients, R² test, of 0.929 and 0.909 for CoMFA and CoMSIA, respectively. Building upon these promising results, eighteen new compounds were designed and assessed for drug likeness and ADMET properties through in silico methods. Additionally, molecular docking studies were conducted to elucidate the binding interactions between the selected compounds and the enzyme. Detailed molecular dynamics simulations were performed to analyze the stability, conformational changes, and binding interactions of the quinazoline derivatives with the EGFR kinase. These simulations provided deeper insights into the dynamic behavior of the compounds within the active site. This comprehensive analysis enhances the understanding of quinazoline derivatives as potential anti-cancer agents and provides valuable insights for lead optimization in the early stages of drug discovery, particularly for developing highly potent anticancer therapeutics

Keywords: 3D-QSAR, CoMFA, CoMSIA, ADMET, molecular docking, quinazoline, molecular dynamic, egfr inhibitors, lung cancer, anticancer

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Authors: Igor V. Kuzminov

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The proposed article is a development of the topics of gravity, the inverse temperature dependence of gravity, the action of the inverse temperature dependence of gravity, and the second law of thermodynamics, dark matter, the identity of gravity, inertial forces, and centrifugal forces. All interaction schemes are built on the basis of Newton's laws of classical mechanics and Rutherford's planetary model of the structure of the atom. The basis of all constructions is the gyroscopic effect of rotation of all particles of the atomic structure. In this case, interatomic and intermolecular bonds are accepted as the static part of the gyroscope, and the rotation of an electron in an atom is accepted as the dynamic part. The structure of the planet Earth is accepted as a model of the structure of the Black Hole. Namely, gravitational and thermodynamic phenomena in the structure of the planet Earth are accepted as a model. Based on this model, assumptions are made about the processes inside the Black Hole. Moreover, a version is put forward, a scheme of a closed cycle of transformation of matter in the Universe.

Keywords: black hole, gravity, inverse temperature dependence of gravitational forces, second law of thermodynamics, gyroscopic effect, dark matter

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Authors: Naveeda Akhtar Qureshi, Wajiha

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Coccidiosis is a protozoan parasitic disease of genus Eimeria. It is an avian infection causing a great economic loss of 3 billion USD per year globally. A number of anticoccidial drugs are in use however many of them have side effects and cost effective. With increase in poultry demand throughout the world there is a need of more drugs and vaccines against coccidiosis. The present study is based upon the use of F. racemosa a medicinal plant to be a potential source of anticoccidial agents. The methanolic leaves extract was fractionated by column and thin layer chromatography and got nineteen fractions. Each fraction different concentrations was evaluated for its anticoccidial properties in an invitro experiment against E. tenella, E. necatrix and E. mitis. The anticoccidial active fractions were further characterized by spectroscopy (UV-Vis, FTIR) and GC-MS analysis. The in silico molecular docking of active fractions identified compounds were carried out. Among all fractions significantly maximum sporulation inhibition efficacy was shown by F-19 (67.11±2.18) followed by F-15 (65.21±1.34) at concentration of 30mg/ml against E. tenella. The significantly highest sporozoites viability inhibition was shown by F-19 (69.23±2.11) followed by F-15 (67.14±1.52) against E. necatrix at concentration 30mg/ml. Anticoccidial active fractions 15 and 19 showed peak spectrum at 207 and 202nm respectively by UV analysis. Their FTIR analysis confirmed the presence of carboxylic acid, amines, phenols, etc. Anticoccidial active compounds like Cyclododecane methanol, oleic acid, Octadecanoic acid, etc were identified by GC-MS analysis. Identified compounds in silico molecular docking study showed that cyclododecane methanol of F-19 and oleic acid of F-15 showed highest binding affinity with target S-Adenosylmethionine synthase. Hence for further authentication in vivo anticoccidial studies are recommended.

Keywords: ficus racemosa, cluster fig, column chromatography, anticoccidial fractions, GC-MS, molecular docking., s-adenosylmethionine synthase

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Authors: Kwan U. Kim, Jin Sim, Ryong Jin Jang, Sung Duk Kim

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It is Leverrier that discovered the precession of the perihelion in the planetary orbits for the first time in the world, while it is Einstein that explained the astronomical phenomenom for the first time in the world. The amount of the precession of the perihelion for Einstein’s theory of gravitation has been explained by means of the inverse fourth power force(inverse third power potential) introduced totheory of gravitation through Schwarzschild metric However, the methodology has a serious shortcoming that it is impossible to explain the cause for the precession of the perihelion in the planetary orbits. According to our study, without taking the cause for the precession of the perihelion, 6 methods can explain the amount of the precession of the perihelion discovered by Leverrier. Therefore, the problem of what caused the perihelion to precess in the planetary orbits must be solved for physics because it is a profound scientific and technological problem for a basic experiment in construction of relativistic theory of gravitation. The scientific solution to the problem proved that Einstein’s explanation for the planetary orbits is a magic made by the numerical expressions obtained from fictitious gravitation introduced to theory of gravitation and wrong definition of proper time The problem of the precession of the perihelion seems solved already by means of general theory of relativity, but, in essence, the cause for the astronomical phenomenon has not been successfully explained for astronomy yet. The right solution to the problem comes from generalized theory of gravitation. Therefore, in this paper, it has been shown that by means of Schwarzschild field and the physical quantities of relativistic Lagrangian redflected in it, fictitious gravitation is not the main factor which can cause the perihelion to precess in the planetary orbits. In addition to it, it has been shown that the main factor which can cause the perihelion to precess in the planetary orbits is the inverse third power force existing really in the relativistic region in the Solar system.

Keywords: inverse third power force, precession of the perihelion, fictitious gravitation, planetary orbits

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Authors: Sakshi Piplani, Ajit Kumar

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Valproic acid (VPA) is the first synthetic therapeutic agent used to treat epileptic disorders, which account for affecting nearly 1% world population. Teratogenicity caused by VPA has prompted the search for next generation drug with better efficacy and lower side effects. Recent studies have posed HDAC8 as direct target of VPA that causes the teratogenic effect in foetus. We have employed molecular dynamics (MD) and docking simulations to understand the binding mode of VPA and their analogues onto HDAC8. A total of twenty 3D-structures of human HDAC8 isoforms were selected using BLAST-P search against PDB. Multiple sequence alignment was carried out using ClustalW and PDB-3F07 having least missing and mutated regions was selected for study. The missing residues of loop region were constructed using MODELLER and energy was minimized. A set of 216 structural analogues (>90% identity) of VPA were obtained from Pubchem and ZINC database and their energy was optimized with Chemsketch software using 3-D CHARMM-type force field. Four major neurotransmitters (GABAt, SSADH, α-KGDH, GAD) involved in anticonvulsant activity were docked with VPA and its analogues. Out of 216 analogues, 75 were selected on the basis of lower binding energy and inhibition constant as compared to VPA, thus predicted to have anti-convulsant activity. Selected hHDAC8 structure was then subjected to MD Simulation using licenced version YASARA with AMBER99SB force field. The structure was solvated in rectangular box of TIP3P. The simulation was carried out with periodic boundary conditions and electrostatic interactions and treated with Particle mesh Ewald algorithm. pH of system was set to 7.4, temperature 323K and pressure 1atm respectively. Simulation snapshots were stored every 25ps. The MD simulation was carried out for 20ns and pdb file of HDAC8 structure was saved every 2ns. The structures were analysed using castP and UCSF Chimera and most stabilized structure (20ns) was used for docking study. Molecular docking of 75 selected VPA-analogues with PDB-3F07 was performed using AUTODOCK4.2.6. Lamarckian Genetic Algorithm was used to generate conformations of docked ligand and structure. The docking study revealed that VPA and its analogues have more affinity towards ‘hydrophobic active site channel’, due to its hydrophobic properties and allows VPA and their analogues to take part in van der Waal interactions with TYR24, HIS42, VAL41, TYR20, SER138, TRP137 while TRP137 and SER138 showed hydrogen bonding interaction with VPA-analogues. 14 analogues showed better binding affinity than VPA. ADMET SAR server was used to predict the ADMET properties of selected VPA analogues for predicting their druggability. On the basis of ADMET screening, 09 molecules were selected and are being used for in-vivo evaluation using Danio rerio model.

Keywords: HDAC8, docking, molecular dynamics simulation, valproic acid

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Authors: Hong Su, Qiuju Yan, Wei Du, En Hu, Zhaoyu Yang, Wei Zhang, Yusheng Li, Tao Tang, Wang yang, Shushan Zhao

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Osteoarthritis (OA) is a severe chronic inflammatory disease. As the main active component of Astragalus mongholicus Bunge, a classic traditional ethnic herb, calycosin exhibits anti-inflammatory action and its mechanism of exact targets for OA have yet to be determined. In this study, we established an anterior cruciate ligament transection (ACLT) mouse model. Mice were randomized to sham, OA, and calycosin groups. Cartilage synthesis markers type II collagen (Col-2) and SRY-Box Transcription Factor 9 (Sox-9) increased significantly after calycosin gavage. While cartilage matrix degradation index cyclooxygenase-2 (COX-2), phosphor-epidermal growth factor receptor (p-EGFR), and matrix metalloproteinase-9 (MMP9) expression were decreased. With the help of network pharmacology and molecular docking, these results were confirmed in chondrocyte ATDC5 cells. Our results indicated that the calycosin treatment significantly improved cartilage damage, this was probably attributed to reversing the imbalance between chondrocyte synthesis and catabolism.

Keywords: calycosin, osteoarthritis, network pharmacology, molecular docking, inflammatory, cyclooxygenase 2

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Authors: Jineetkumar Gawad, Chandrakant Bonde

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Tuberculosis (TB) is a major worldwide concern whose control has been exacerbated by HIV, the rise of multidrug-resistance (MDR-TB) and extensively drug resistance (XDR-TB) strains of Mycobacterium tuberculosis. The interest for newer and faster acting antitubercular drugs are more remarkable than any time. To search potent compounds is need and challenge for researchers. Here, we tried to design lead for inhibition of Decaprenyl phosphoryl-β-D-ribose 2′-epimerase (DprE1) enzyme. Arabinose is an essential constituent of mycobacterial cell wall. DprE1 is a flavoenzyme that converts decaprenylphosphoryl-D-ribose into decaprenylphosphoryl-2-keto-ribose, which is intermediate in biosynthetic pathway of arabinose. Latter, DprE2 converts keto-ribose into decaprenylphosphoryl-D-arabinose. We had a selection of 23 compounds from azaindole series for computational study, and they were drawn using marvisketch. Ligands were prepared using Maestro molecular modeling interface, Schrodinger, v10.5. Common pharmacophore hypotheses were developed by applying dataset thresholds to yield active and inactive set of compounds. There were 326 hypotheses were developed. On the basis of survival score, ADRRR (Survival Score: 5.453) was selected. Selected pharmacophore hypotheses were subjected to virtual screening results into 1000 hits. Hits were prepared and docked with protein 4KW5 (oxydoreductase inhibitor) was downloaded in .pdb format from RCSB Protein Data Bank. Protein was prepared using protein preparation wizard. Protein was preprocessed, the workspace was analyzed using force field OPLS 2005. Glide grid was generated by picking single atom in molecule. Prepared ligands were docked with prepared protein 4KW5 using Glide docking. After docking, on the basis of glide score top-five compounds were selected, (5223, 5812, 0661, 0662, and 2945) and the glide docking score (-8.928, -8.534, -8.412, -8.411, -8.351) respectively. There were interactions of ligand and protein, specifically HIS 132, LYS 418, TRY 230, ASN 385. Pi-pi stacking was observed in few compounds with basic Imidazo [4,5-b] pyridine ring. We had basic azaindole ring in parent compounds, but after glide docking, we received compounds with Imidazo [4,5-b] pyridine as a basic ring. That might be the new lead in the process of drug discovery.

Keywords: DprE1 inhibitors, in silico drug designing, imidazo [4, 5-b] pyridine, lead, tuberculosis

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Authors: Muhammad Hassan Khalil, Xu Jiadong

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Early detection through screening is the best tool short of a perfect treatment against the malignant tumor inside the breast of a woman. By detecting cancer in its early stages, it can be recognized and treated before it has the opportunity to spread and change into potentially dangerous. Microwave tomography is a new imaging method based on contrast in dielectric properties of materials. The mathematical theory of microwave tomography involves solving an inverse problem for Maxwell’s equations. In this paper, we present designed antenna for breast cancer detection, which will use in microwave tomography configuration.

Keywords: microwave imaging, inverse scattering, breast cancer, malignant tumor detection

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Authors: Benarous Khedidja, Yousfi Mohamed

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Infections caused by Candida species manifest in a number of diseases, including candidemia, vulvovaginal candidiasis, endocarditis, and peritonitis. These Candida species have been reported to have lipolytic activity by secretion of lipolytic enzymes such as esterases, lipases and phospholipases. These Extracellular hydrolytic enzymes seem to play an important role in Candida overgrowth. Candidiasis is commonly treated with antimycotics such as clotrimazole and nystatin, which bind to a major component of the fungal cell membrane (ergosterol). This binding forms pores in the membrane that lead to death of the fungus. Due to their secondary effects, scientists have thought of another treatment basing on lipase inhibition but we haven’t found any lipase inhibitors used as candidiasis treatment. In this work, we are interested to lipases inhibitors such as alkaloids as another candidiasis treatment. In the first part, we have proceeded to optimize the alkaloid structures and protein 3D structure using Hyperchem software. Secondly, we have docked inhibitors using Genetic algorithm with GOLD software. The results have shown ten possibilities of binding inhibitor to Candida rugosa lipase (CRL) but only one possibility has been accepted depending on the weakest binding energy.

Keywords: marrubiin, candida rugosa lipase, docking, gold

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Authors: Srinivasarao Kondaparla, Utsab Debnath, Awakash Soni, Vasantha Rao Dola, Manish Sinha, Kumkum Kumkum Srivastava, Sunil K. Puri, Seturam B. Katti

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In a focused exploration, we have designed synthesized and biologically evaluated chiral conjugated new chloroquine (CQ) analogs with substituted piperazines as antimalarial agents. In vitro as well as in vivo studies revealed that compound 7c showed potent activity [for in vitro IC₅₀= 56.98nM (3D7), 97.76nM (K1); for in vivo (up to at the dose of 12.5 mg/kg); SI = 3510] as a new lead of antimalarial agent. Other compounds 6b, 6d, 7d, 7h, 8c, 8d, 9a, and 9c are also showing moderate activity against CQ-sensitive (3D7) strain and superior activity against resistant (K1) strain of P. falciparum. Furthermore, we have carried out docking and 3D-QSAR studies of all in-house data sets (168 molecules) of chiral CQ analogs to explain the structure activity relationships (SAR). Our new findings specified the significance of H-bond interaction with the side chain of heme for biological activity. In addition, the 3D-QSAR study against 3D7 strain indicated the favorable and unfavorable sites of CQ analogs for incorporating steric, hydrophobic and electropositive groups to improve the antimalarial activity.

Keywords: piperazines, CQ-sensitive strain-3D7, in-vitro and in-vivo assay, docking, 3D-QSAR

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Authors: Ashis Mallick, Rajeev Ranjan

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The closed form solution for thermal stresses in an annular fin with hyperbolic profile is derived using Adomian decomposition method (ADM). The conductive-convective fin with variable thermal conductivity is considered in the analysis. The nonlinear heat transfer equation is efficiently solved by ADM considering insulated convective boundary conditions at the tip of fin. The constant of integration in the solution is to be estimated using minimum decomposition error method. The solution of temperature field is represented in a polynomial form for convenience to use in thermo-elasticity equation. The non-dimensional thermal stress fields are obtained using the ADM solution of temperature field coupled with the thermo-elasticity solution. The influence of the various thermal parameters in temperature field and stress fields are presented. In order to show the accuracy of the ADM solution, the present results are compared with the results available in literature. The stress fields in fin with hyperbolic profile are compared with those of uniform thickness profile. Result shows that hyperbolic fin profile is better choice for enhancing heat transfer. Moreover, less thermal stresses are developed in hyperbolic profile as compared to rectangular profile. Next, Nelder-Mead based simplex search method is employed for the inverse estimation of unknown non-dimensional thermal parameters in a given stress fields. Owing to the correlated nature of the unknowns, the best combinations of the model parameters which are satisfying the predefined stress field are to be estimated. The stress fields calculated using the inverse parameters give a very good agreement with the stress fields obtained from the forward solution. The estimated parameters are suitable to use for efficient and cost effective fin designing.

Keywords: Adomian decomposition, inverse analysis, hyperbolic fin, variable thermal conductivity

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Authors: Minho Kwon, Seonghyeok Lee, Wooyoung Jung

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In recent years, with increase of construction of skyscraper structures, the study of concrete materials to improve their weight and performance has been emerging as a key of research area. Typically, the concrete structures has disadvantage of increasing the weight due to its mass in comparison to the strength of the materials. Therefore, in order to improve such problems, the light-weight aggregate concrete and high strength concrete materials have been studied during the past decades. On the other hand, the study of light-weight aggregate concrete materials has lack of data in comparison to the concrete structure using high strength materials, relatively. Consequently, this study presents the performance characteristics of light-weight aggregate concrete materials due to the material properties and strength. Also, this study conducted the experimental tests with respect to normal and lightweight aggregate materials, in order to indentify the tensile crack failure of the concrete structures. As a result, the Crack Mouth Opening Displacement (CMOD) from the experimental tests was constructed and the fracture energy using inverse problem analysis was developed from the force-CMOD relationship in this study, respectively.

Keywords: lightweight aggregate concrete, crack mouth opening displacement, inverse analysis, fracture energy

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Authors: Kabrambam D. Singh, Dinabandhu Sahoo, Yallappa Rajashekar

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Evolution has caused many insects to develop resistance to several synthetic insecticides. This problem along with the persisting concern regarding the health and environmental safety issues of the existing synthetic insecticides has urged the scientific fraternity to look for a new plant-based natural insecticide with inherent eco-friendly nature. Colocasia esculenta var. esculenta (L.) Schott (Araceae family) is widely grown throughout the South- East Asian Countries for its edible corms and leaves. Various physico-chemical and spectroscopic techniques (IR, 1H NMR, 13C NMR and Mass) were used for the isolation and characterization of isolated bioactive molecule named 2, 3-dimethylmaleic anhydride (3, 4-dimethyl-2, 5-furandione). This compound was found to be highly toxic, even at low concentration, against several storage grain pests when used as biofumigant. Experimental studies on the mode of action of 2, 3-dimethylmaleic anhydride revealed that the biofumigant act as inhibitor of acetylcholinesterase enzyme in cockroach and stored grain insects. The knockdown activity of bioactive compound is concurrent with in vivo inhibition of AChE; at KD99 dosage of bioactive molecule showed more than 90% inhibition of AChE activity in test insects. The molecule proved to affect the antioxidant enzyme system; superoxide dismutase (SOD), and catalase (CAT) and also found to decrease reduced glutathione (GSH) level in the treated insects. The above results indicate involvement of inhibition of AChE activity and oxidative imbalance as the potential mode of action of 2, 3-dimethylmaleic anhydride. In addition, the study reveals computational docking programs elaborate the possible interaction of 2, 3-dimethylmaleic anhydride with enzyme acetylcholinesterase (AChE) of Periplaneta americana. Finally, the results represent that toxicity of 2, 3-dimethylmaleic anhydride might be associated with inhibition of AChE activity and oxidative imbalance.

Keywords: 2, 3-dimethylmaleic anhydride, Colocasia esculenta var. esculenta (L.) Schott, Biofumigant, acetylcholinesterase, antioxidant enzyme, molecular docking

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Authors: Hammed Tanimowo Aiyelabegan, Oluchukwu Franklin Aladi, Mutiu Adewumi Alabi, Raliat Abimbola Aladodo, Emmanuel Oladipupo Ajani, Abdulganiyu Giwa, Esther Owolabi

Abstract:

The study aimed to evaluate the inhibitory activities of ligands from Enantia chlorantha stem bark on α-amylase and α-glucosidase. In silico pharmacokinetic properties and docking scores were employed to analyse the inhibition using SwissADME and Autodock4.2, respectively. Results revealed that drug-likeness, pharmacokinetics and bioavailability radar of all the ligands except jatrorrhizine and acarbose falls within the radar according to the Lipinski rule of 5. The binding energies of the protein-ligand interactions also show that the ligand fits into the active site. The results obtained from this study show that the chemical constituents from Enantia chlorantha stem bark may bring about positive physiological changes in a patient suffering from diabetes mellitus. Further in vitro studies on diabetes cell lines and in vivo studies on the animal may validate these compounds for diabetes treatment. These phytoconstituents could help in the development of novel anti-diabetic molecules.

Keywords: diabetes mellitus, ?-amylase, ?-glucosidase, in silico, Enantia chlorantha stem bark

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Authors: Mouna Baassi, Mohamed Moussaoui, Sanchaita Rajkhowa, Hatim Soufi, Said Belaaouad

Abstract:

The objective of this paper is to address the challenging task of targeting Human Immunodeficiency Virus type 1 Reverse Transcriptase (HIV-1 RT) in the treatment of AIDS. Reverse Transcriptase inhibitors (RTIs) have limitations due to the development of Reverse Transcriptase mutations that lead to treatment resistance. In this study, a combination of statistical analysis and bioinformatics tools was adopted to develop a mathematical model that relates the structure of compounds to their inhibitory activities against HIV-1 Reverse Transcriptase. Our approach was based on a series of compounds recognized for their HIV-1 RT enzymatic inhibitory activities. These compounds were designed via software, with their descriptors computed using multiple tools. The most statistically promising model was chosen, and its domain of application was ascertained. Furthermore, compounds exhibiting comparable biological activity to existing drugs were identified as potential inhibitors of HIV-1 RT. The compounds underwent evaluation based on their chemical absorption, distribution, metabolism, excretion, toxicity properties, and adherence to Lipinski's rule. Molecular docking techniques were employed to examine the interaction between the Reverse Transcriptase (Wild Type and Mutant Type) and the ligands, including a known drug available in the market. Molecular dynamics simulations were also conducted to assess the stability of the RT-ligand complexes. Our results reveal some of the new compounds as promising candidates for effectively inhibiting HIV-1 Reverse Transcriptase, matching the potency of the established drug. This necessitates further experimental validation. This study, beyond its immediate results, provides a methodological foundation for future endeavors aiming to discover and design new inhibitors targeting HIV-1 Reverse Transcriptase.

Keywords: QSAR, ADMET properties, molecular docking, molecular dynamics simulation, reverse transcriptase inhibitors, HIV type 1

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

Abstract:

The complexes of transition metals with various organic ligands have been extensively studied as models of some important pharmaceutical molecules. It was found that biological properties of different substituted organic molecules are improved when they are complexed by different metals. Therefore, it is of great importance for the development of coordination chemistry to explore the assembly of functional organic ligands with metal ion and to investigate the relationship between the structure and property. In the present work, we have bioassayed the antibacterial potency of benzimidazoles and their metal salts (Cu or Zn) against yeast Sarcina lutea. In order to validate our in vitro study, we performed in silico studies using molecular docking software. The investigated compounds and their metal complexes (Cu, Zn) showed good to moderate inhibitory activity against Sarcina lutea. In silico docking studies of the synthesized compounds suggested that complexed benzimidazoles have a greater binding affinity and improved antibacterial activity in comparison with non-complexed ligands. These results are part of the CMST COST Action No. 1105 "Functional metal complexes that bind to biomolecules".

Keywords: organometallic complexes, benzimidazoles, chemometric design, Sarcina lutea

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Authors: Hind O. Osman, Tilal Elsaman, Bashir A. Yousef, Esraa Elhadi, Aimun A. E. Ahmed, Eyman Mohamed Eltayib, Malik Suliman Mohamed, Magdi Awadalla Mohamed

Abstract:

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

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Authors: Mengjun Yang, Zhulin Zong, Jie Gao

Abstract:

In this paper, a new and robust algorithm is proposed to achieve high resolution for inverse synthetic aperture radar (ISAR) imaging in the compressive sensing (CS) framework. Traditional CS based methods have to assume that unknown scatters exactly lie on the pre-divided grids; otherwise, their reconstruction performance dropped significantly. In this processing algorithm, several basis shifts are utilized to achieve the same effect as grid refinement does. The detailed implementation of the basis shift algorithm is presented in this paper. From the simulation we can see that using the basis shift algorithm, imaging precision can be improved. The effectiveness and feasibility of the proposed method are investigated by the simulation results.

Keywords: ISAR imaging, sparse reconstruction, off-grid, basis shift

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Authors: Yanli Qi, Ning Lv, Jing Li

Abstract:

Sub-Nyquist sampling jamming method (SNSJ) is a well known deception jamming method for inverse synthetic aperture radar (ISAR). However, the anti-decoy of the SNSJ method performs easier since the amplitude of the false-target images are weaker than the real-target image; the false-target images always lag behind the real-target image, and all targets are located in the same cross-range. In order to overcome the drawbacks mentioned above, a simple modulation based on SNSJ (M-SNSJ) is presented in this paper. The method first uses amplitude modulation factor to make the amplitude of the false-target images consistent with the real-target image, then uses the down-range modulation factor and cross-range modulation factor to make the false-target images move freely in down-range and cross-range, respectively, thus the capacity of deception is improved. Finally, the simulation results on the six available combinations of three modulation factors are given to illustrate our conclusion.

Keywords: inverse synthetic aperture radar (ISAR), deceptive jamming, Sub-Nyquist sampling jamming method (SNSJ), modulation based on Sub-Nyquist sampling jamming method (M-SNSJ)

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Authors: Mohsen S. Sajadieha, Danyar Molavia

Abstract:

In this paper, a truck scheduling problem is investigated at a two-touch cross-docking center with due dates for outbound trucks as a hard constraint. The objective is to minimize the total cost comprising penalty and delivery cost of delayed shipments. The sequence of unloading shipments is considered and is assumed that shipments are sent to shipping dock doors immediately after unloading and a First-In-First-Out (FIFO) policy is considered for loading the shipments. A mixed integer programming model is developed for the proposed model. Two meta-heuristic algorithms including genetic algorithm (GA) and variable neighborhood search (VNS) are developed to solve the problem in medium and large sized scales. The numerical results show that increase in due dates for outbound trucks has a crucial impact on the reduction of penalty costs of delayed shipments. In addition, by increase the due dates, the improvement in the objective function arises on average in comparison with the situation that the cross-dock is multi-touch and shipments are sent to shipping dock doors only after unloading the whole inbound truck.

Keywords: cross-docking, truck scheduling, fixed due date, door assignment

Procedia PDF Downloads 404