The prostaglandins inside inflamed tissues are produced by cyclooxygenase-2 (COX-2), making it an important target for improving anti-inflammatory medications over a long period. Adverse effects have been related to the traditional usage of non-steroidal anti-inflammatory drugs (NSAIDs) for the treatment of inflammation, mainly centered around gastrointestinal (GI) complications. The current research involves the creation of a virtual library of innovative molecules showing similar drug properties via a structure-based drug design. A library that includes five novel derivatives of Diclofenac was designed. Subsequently, molecular docking through the Glide module and determining the binding free energy implementing the Prime-MMGBSA module by the Schrödinger software package was used to identify compounds that showed marked specificity towards the COX-2 isoform. In addition, the ligands are subject to evaluation of their drug-like properties and ADMET (absorption, distribution, metabolism, excretion, and toxicity) characteristics using the QikProp module. Finally, molecular dynamics simulation has been calculated for the best molecule. The docking results indicated that all compounds own a predictive capability for specific binding to the COX-2 enzyme compared to the standard drug with a docking score range from -10.07 to -10.66 Kcal/mole, thus potentially overcoming the limitations imposed previously by the drugs currently used in clinical use. The ADMET analysis of the virtually active compounds demonstrated an acceptable drug-like profile and desirable pharmacokinetics properties. MM/GBSA calculation revealed that all the suggested compounds exhibited favorable free binding energies (-49.150 to - 60.185 Kcal/mole), indicating their strong potential to fit well into the COX-2 receptor. Finally, the MD simulation study revealed that compound 1 had perfect alignment with COX-2 receptor. The findings indicated that the compounds possess a predictive capability for specific binding to the COX-2 enzyme, thus potentially surmounting the restrictions imposed by the drugs currently employed in clinical use.
Abstract
Although the rapid development in reverse engineering techniques, 3D laser scanners can be considered the modern technology used to digitize the 3D objects, but some troubles may be associate this process due to the environmental noises and limitation of the used scanners. So, in the present paper a data pre-processing algorithm has been proposed to obtain the necessary geometric features and mathematical representation of scanned object from its point cloud which obtained using 3D laser scanner (Matter and Form) through isolating the noised points. The proposed algorithm based on continuous calculations of chord angle between each adjacent pair of points in point cloud. A MATLAB program has been built t
... Show MoreAbstract: Tin oxide thin films were deposited by direct current (DC) reactive sputtering at gas pressures of 0.015 mbar – 0.15 mbar. The crystalline structure and surface morphology of the prepared SnO2 films were introduced by X-ray diffraction (XRD) and atomic force microscopy (AFM). These films showed preferred orientation in the (110) plane. Due to AFM micrographs, the grain size increased non-uniformly as the working gas pressure increased.
Sewer sediment deposition is an important aspect as it relates to several operational and environmental problems. It concerns municipalities as it affects the sewer system and contributes to sewer failure which has a catastrophic effect if happened in trunks or interceptors. Sewer rehabilitation is a costly process and complex in terms of choosing the method of rehabilitation and individual sewers to be rehabilitated. For such a complex process, inspection techniques assist in the decision-making process; though, it may add to the total expenditure of the project as it requires special tools and trained personnel. For developing countries, Inspection could prohibit the rehabilitation proceeds. In this study, the researchers propos
... Show MoreHigh-volume traffic with ultra-heavy axle loads combined with extremely hot weather conditions increases the propagation of rutting in flexible pavement road networks. Several studies suggested using nanomaterials in asphalt modification to delay the deterioration of asphalt pavement. The current work aims to improve the resistance of hot mix asphalt (HMA) to rutting by incorporating Nano Silica (NS) in specific concentrations. NS was blended into asphalt mixtures in concentrations of 2, 4, and 6% by weight of the binder. The behavior of asphalt mixtures subjected to aging was investigated at different stages (short-term and long-term aging). The performance characteristics of the asphalt mixtures were evaluated using the Marshall s
... Show MoreA simple ,accurate and sensitive spectrophotometric method has been developed the determination of Cobalt(II) and Cupper (II) .The method is based on the chelation of Co(II) and Cu(II) ions with 4-(4´-pyrazolon azo) -2-Naphthol(APAN) in aqueous medium . The complexes have a maximum absorption at (513) and (506) nm and ? max 0.531×10 4 and 0.12×10 5 L.mol -1.cm -1 for Co(II) and Cu(II) respectively .The reagent and two complexes have been prepared in ethanolic solution.The stoichiometry of both complexes were found to be 1:2 (metal :legend) .The effects of various cations and anions on Co(II) and Cu(II) determination have been investigated .The stability constants and standard deviations for Co(II) and Cu(II) 0.291 x107 ,0.909X108 L.mol
... Show MoreMachine Learning (ML) algorithms are increasingly being utilized in the medical field to manage and diagnose diseases, leading to improved patient treatment and disease management. Several recent studies have found that Covid-19 patients have a higher incidence of blood clots, and understanding the pathological pathways that lead to blood clot formation (thrombogenesis) is critical. Current methods of reporting thrombogenesis-related fluid dynamic metrics for patient-specific anatomies are based on computational fluid dynamics (CFD) analysis, which can take weeks to months for a single patient. In this paper, we propose a ML-based method for rapid thrombogenesis prediction in the carotid artery of Covid-19 patients. Our proposed system aims
... Show MoreA simple technique is proposed in this paper for estimating the coefficient of permeability of an unsaturated soil based on physical properties of soils that include grain size analysis, degree of saturation or water content, and porosity of the soil. The proposed method requires the soil-water characteristic curve for the prediction of the coefficient of permeability as most of the conventional methods. A procedure is proposed to define the hydraulic conductivity function from the soil water characteristic curve which is measured by the filter paper method. Fitting methods are applied through the program (SoilVision), after indentifying the basic properties of the soil such as Attereberg limits, specific gravity, void ratio, porosity, d
... Show MoreThe influence of an aortic aneurysm on blood flow waveforms is well established, but how to exploit this link for diagnostic purposes still remains challenging. This work uses a combination of experimental and computational modelling to study how aneurysms of various size affect the waveforms. Experimental studies are carried out on fusiform-type aneurysm models, and a comparison of results with those from a one-dimensional fluid–structure interaction model shows close agreement. Further mathematical analysis of these results allows the definition of several indicators that characterize the impact of an aneurysm on waveforms. These indicators are then further studied in a computational model of a systemic blood flow network. This demonstr
... Show More