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.
The new compounds of pyrazolines were synthesized from the reaction of different acid hydrazide with ethylacetoacetate and ethanol under reflux. These compounds were obtained from many sequence reactions. The 4-acetyl-5-methyl-2,4-dihydro-3H-pyrazol-3-one compounds synthesized from the reaction of 5-methyl-2,4-dihydro-3H-pyrazol-3-one with acetyl chloride in calcium hydroxide and 1,4-dioxane. Finaly, Schiff bases were prepared via condensation reaction of products of mono- and tri ketone derivatives[IV]a, b with phenyl hydrazines as presented in (Scheme 1, 2). The synthesized compounds were identification by using FTIR, NMR and Mass spectroscopy (of some of them).
Cystic conditions of the jaw cause bony destruction and may cause resorption or displacement of adjacent teeth. Odontogenic cysts have developmental or inflammatory origins. To describe in detail the inflammatory odontogenic cysts, a manual search was done in hard copy books of oral and maxillofacial pathology, and an electronic search was done in the google website, oral and maxillofacial pathology E-books, PubMed, Research Gate, Academia, and Google scholar using the keywords "odontogenic cysts," "classification of the odontogenic cysts," "radicular cyst," "periapical cyst," "lateral inflammatory cyst," "residual cyst," "paradental cyst," "collateral inflammatory cyst," "treatment of inflammatory odontogenic cysts," and matching
... Show MoreThe present work involved designing and synthesizing of a series of new. compounds which their molecules are composed from two biologically active components namely sulfamethoxazole or β-lactam containing drugs and cyclic imides. The target new compounds were synthesized by two steps in the first one a series of six bis (N-drug phthalamic acid_4-yl) ketone (1-6) were prepared from the reaction of sulfamethoxazole or β-lactam containing drugs with benzophenone 3, 3′, 4, 4′ -tetracarboxylic dianhydride.
In the second step, compounds (1-6) were introduced in dehydration reaction via fusion process producing the target compounds bis (N-drug phthalimidyl-4-yl) ketone (7-12). The antibacterial and antifungal high
... Show MoreThe need for Dewatering is very important in construction workshops field and sometimes it needs to pay more attention as a result of its impacts on causing additional settlement of nearby pile foundations. Dewatering construction may become a costly topic if ignored during project planning and designing .In this paper a simplified procedure maybe adopted to calculate the foundation settlement induced by using dewatering system which is required to lower the water table level to reach a dry condition during construction. Synthesized case study adopted at a specified location in Baghdad city and analysis are computed for two types of piles both of them are submerged with water. Results shows the effect of dewatering on pile foundatio
... Show MoreThe aim of this research is to compare traditional and modern methods to obtain the optimal solution using dynamic programming and intelligent algorithms to solve the problems of project management.
It shows the possible ways in which these problems can be addressed, drawing on a schedule of interrelated and sequential activities And clarifies the relationships between the activities to determine the beginning and end of each activity and determine the duration and cost of the total project and estimate the times used by each activity and determine the objectives sought by the project through planning, implementation and monitoring to maintain the budget assessed
... Show MoreIn cooling water systems, cooling towers play a critical role in removing heat from the water. Cooling water systems are commonly used in industry to dispose the waste heat. An upward spray cooling water systems was especially designed and investigated in this work. The effect of two nanofluids (Al2O3/ water, black carbon /water) on velocity and temperature distributions along reverse spray cooling tower at various concentrations (0.02, 0.08, 0.1, 0.15, and 0.2 wt.%) were investigated, beside the effect of the inlet water temperature (35 ,40, and 45 ͦ C) and water to air flow ratio (L/G) of 0.5, 0.75, and 1. The best thermal performance was found when the working solution contained 0.1 wt.% for each of Al2
... Show MoreCo-crystals are new solid forms of drugs that could resolve more than one problem associated with drugs formulations like solubility, stability, bioavailability, mechanical and tableting properties. A preliminary theoretical study for estimating the possible bonding between the co-crystal components (paracetamol and naproxen) was performed using the ChemOffice program. The results revealed a high possibility for bonding between paracetamol and naproxen and indicated the ability of molecular mechanics study to predict the co-crystal design.
In this work, four different methods were used for the preparation of three different ratios 1:1, 2:1, and 1:2 of paracetamol:naproxen co-crystals. The four
... Show MoreThe design was distinguished in Late Twenty-First Century With new and new methods Through which the ability to adapt all technical media in the formation of two-dimensional and three-dimensional figures and shapes was achieved .
Which led to the emergence of endless sets of design ideas characterized by the heterogeneity of design forms and design solutions that preceded it. The designer could not access these creations in various architectural and artistic fields only through computer programs, especially those related to the activation of mathematical logic and what is known as algorithms in the formation and construction of the form, which led to the emergence of the "parametric direction" and the problem of research is summarized