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 As the United Nations approaches its 70th anniversary, the world is going through the most severe accumulation of serious international security failures in recent memory, challenging the UN Security Council’s ability to address them effectively. Over the past four years, crises in Libya, Syria and Ukraine have precipitated a worrisome erosion of great power relations that has complicated Security Council decision making on a number of trouble spots. Its inability to devise consensus responses to the escalating civil war in Syria has been particularly troubling, resulting in the regional spill over into Iraq and the emergence of Islamic State as a new threat to peace in the region and beyond. Meanwhile, the UN’s often under
... Show MoreSearch marked (the reflection of diode technology light emitting (LED) on the modular design of external lighting) is an analytical study of the units, external lighting for gardens and adopted in its work on the diode technology emitting light to reach the magnitude of the effect and the change happening where according to this technique was the problem of the research in which is (what emotion the formal and functional units of external lighting according diode technology light emitting) and identified in the first part of it, including the goals came Search of b (statement reversal winning technical transformation of lighting from incandescent bulbs to light emitting diode technology (LED) on each of shape design and the nature of the
... Show MoreDiverting river flow during construction of a main dam involves the construction of cofferdams, and tunnels, channels or other temporary passages. Diversion channels are commonly used in wide valleys where the high flow makes tunnels or culverts uneconomic. The diversion works must form part of the overall project design since it will have a major impact on its cost, as well as on the design, construction program and overall cost of the permanent works. Construction costs contain of excavation, lining of the channel, and construction of upstream and downstream cofferdams. The optimization model was applied to obtain optimalchannel cross section, height of upstream cofferdam, and height of downstream cofferdamwith minimum construction cost
... Show MoreThe water supply network inside the building is of high importance due to direct contact with the user that must be optimally designed to meet the water needs of users. This work aims to review previous research and scientific theories that deal with the design of water networks inside buildings, from calculating the amount of consumption and the optimal distribution of the network, as well as ways to rationalize the use of water by the consumer. The process of pumping domestic water starts from water treatment plants to be fed to the public distribution networks, then reaching a distribution network inside the building till it is provided to the user. The design of the water supply network inside the building is
... Show MoreObjectives. This study aimed at finding out whether anterior teeth angulation and inclination have a relationship with the maxillary teeth and dental arch dimensions. Methods. Fifty study models with normal occlusion were selected from the archive of the Department of Orthodontics at Baghdad Dental Faculty. Maxillary dental arch width and length at different points were determined in addition to measuring anterior teeth angulation, inclination, crown thickness, overjet, overbite, and Bolton’s ratios. The unpaired t-test and Pearson’s correlation coefficient test were used for data analysis. Results. No statistical gender differences were reported in all measurements except the dental arch widths and length where males had signif
... Show MoreHuman beings have an innate and natural aim to achieve their self-interests and to show their ability to overcome challenges in a better way, therefore the move towards self determination is expressed by intrinsic motivation. The desire of absorbing in this task is to enjoy the task in it self and benefitting from it such a motivation is the desire rooted in human nature to judge and choose in which individual is conscious in his self, abilities and adequacy that help him in control the different situations of life passed by him. His choices and actions are voluntary and non-restricted to intervention or external control because control is inner and subjective, while his behavior is self-regulated with the feeling of
... Show More