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 Background: Viral hepatitis places a heavy burden on the health care. Large number of patient with bleeding disorders has chronic hepatitis C infection, while few are chronic carriers of hepatitis B virus. Aims of study: evaluate the prevalence of HBV, HCV infection among patient with Von Willebrand disease and to find factors that associated with the chance of getting the infection.
The activity of Alanine aminopeptidase( AAP ) was measured in the urine of healthy and urinary tract cancer patients , the results showed higher activity of (AAP) in patients compared to healthy . AAP was Purified from the urine of healthy and patients with urinary tract cancer by dialysis and gel filtration (Sephadex G – 50) and two isoenzymes of (AAP) were separated from urine by using ion-exchang resin (DEAE – Sephadex A – 50 ) in previous study. The kinetics studies showed that both isoenzymes I and II obeyed Michaelis – Menton equation . with optimal concentration of alanine-4-nitroanilide as substrate for isoenzymes I and II which was (2 x 10-3 mol/L ). The two isoenzymes obeyed Arrhenius equation up two 37° C and t
... Show MoreAbsence or hypoplasia of the internal carotid artery (ICA) is a rare congenital anomaly that is mostly unilateral and highly associated with other intracranial vascular anomalies, of which saccular aneurysm is the most common. Blood flow to the circulation of the affected side is maintained by collateral pathways, some of which include the anterior communicating artery (Acom) as part of their anatomy. Therefore, temporary clipping during microsurgery on Acom aneurysms in patients with unilateral ICA anomalies could jeopardize these collaterals and place the patient at risk of ischemic damage. In this paper, we review the literature on cases with a unilaterally absent ICA associa
In this paper, a procedure to establish the different performance measures in terms of crisp value is proposed for two classes of arrivals and multiple channel queueing models, where both arrival and service rate are fuzzy numbers. The main idea is to convert the arrival rates and service rates under fuzzy queues into crisp queues by using graded mean integration approach, which can be represented as median rule number. Hence, we apply the crisp values obtained to establish the performance measure of conventional multiple queueing models. This procedure has shown its effectiveness when incorporated with many types of membership functions in solving queuing problems. Two numerical illustrations are presented to determine the validity of the
... Show MoreHydrate dissociation equilibrium conditions for carbon dioxide + methane with water, nitrogen + methane with water and carbon dioxide + nitrogen with water were measured using cryogenic sapphire cell. Measurements were performed in the temperature range of 275.75 K–293.95 K and for pressures ranging from 5 MPa to 25 MPa. The resulting data indicate that as the carbon dioxide concentration is increased in the gas mixture, the gas hydrate equilibrium temperature increases. In contrast, by increasing the nitrogen concentration in the gas mixtures containing methane or carbon dioxide decreased the gas hydrate equilibrium temperatures. Furthermore, the cage occupancies for the carbon dioxide + methane system were evaluated using the Van der Wa
... Show MoreBackground: Diabetic is a chronic systemic disorder of glucose metabolism. That could be diagnosed using fasting and/or random plasma glucose and Glycated Haemoglobin (HbA1c). Several biochemical and microbial alterations of saliva could affect dental caries occurrence and severity among diabetic patients. The aim of the present study was to assess the relation of salivary glucose with severity of dental caries and Mutans Streptococci, among uncontrolled and controlled diabetic groups in comparison with non-diabetic control group. Materials and Methods: The total sample composed of adults aged (18-22) years. Divided into 25 uncontrolled diabetic patients (HbA1c > 7), 25 controlled diabetic patients (HbA1c ≤ 7), in addition to 25 no
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