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.
Throughout history, artists have played many important roles in society.
Generally speaking, the role of the artist is defined by the society he is part of.
Indeed, there are as many ideas as to the role of the artist and, ultimately the purpose
of art in society, as there are types of art. This is, as a matter of fact, neither a new
question- the dialogue has been present within art for centuries- nor probably one
that will ever fully be answered.
Tom Stoppard came to prominence in the mid-sixties, when art and politics
were closely linked, and theatre sought to change the world. Stoppard would have
none of that: his work has no overt message, no political program. In fact,
... Show MorePhysiological status and litter size can indeed have a significant impact on ewes' hematological parameters, which are essential indicators of their health. Therefore, this study examined the hematological profiles of ewes during pregnancy with single and twins in the Awassi ewes. The present study involved 232 ewes in good health and at sexual maturity. Among them, 123 ewes had single pregnancies, while 109 ewes had twin pregnancies. The age range of the ewes included in the study was between 3.5 and 4.5 years. Hematological tests were conducted on the sheep's blood samples promptly following collection. The findings demonstrated variations in hematological parameters among pregnant
... Show More: zonal are included in phraseological units, form metaphorical names for a person, give him various emotional and evaluative characteristics. This article examines the topic of zoomorphic metaphors that characterize a person in the Russian and Arabic languages in the aspect of their comparative analysis, since the comparative analysis of the metaphorical meanings of animalisms is an important method for studying cultural linguistics, since zoomorphic metaphors are a reflection of culture in a language.
Since the emergence of the science of international relations as an independent academic scientific field, various theories and trends have appeared and have tried to understand and explain the international reality and give a clear picture of what is happening within the international system of interactions and influences and the search for tools for stability and peace in international relations. Among these theories is the feminist theory, which is a new intellectual trend on the level of international relations theories, which tried to give an explanation of what is happening in world politics and in international relations in particular. The main issue that feminist theory is concerned with is the lack of women’s subordination
... Show MoreThe standard formulation of Wave Intensity Analysis (WIA) assumes that the flow velocity (U) in the conduit is <;<; the velocity of propagation of waves (c) in the system, and Mach number, M=U/c, is negligible. However, in the large conduit arteries, U is relatively high due to ventricular contraction and c is relatively low due to the large compliance; thus M is > 0, and may not be ignored. Therefore, the aim of this study is to identify experimentally the relationship between M and the reflection coefficient in vitro. Combinations of flexible tubes, of 2 m in length with isotropic and uniform circular cross sectional area along their longitudinal axes, were used to present mother and daughter tubes to produce a range of reflection coeffic
... Show MoreBackground: Acute urinary tract infection is a common bacterial infection causing illness in infants and children. At age of seven, 8% of girls and 2% of boys will have at least one episode. Although drinking water and using home remedies are known to help to flush away bacteria and keeps them from sticking to the bladder wall, researches to test the efficacy and safety of hydrochlorothiazide's diuretic effect as adjuvant to the antibiotics in pediatric age groups are lacking, and so this research was to address this subject.
Objectives: To assess the effectiveness and the safety of hydrochlorothiazide as adjuvant therapy to the antibiotics in treating acute urinary tract infect
... Show MoreThe aims of this study are to measure the defect rate and analyze the problems of production of ready concrete mixture plant by using Six Sigma methodology which is a business strategy for operations improvement depending basically on the application of its sub-methodology DMAIC improvement cycle and the basic statistical tools where the process sigma level of concrete production in the case study was 2.41 σ.