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.
In this work pyrazolin derivatives were prepared from the diazonium chloride salt of 4-aminobenzoic acid. Azo compounds were prepared from the reaction of an ethanolic solution of sodium acetate and calculated amount of active methylene compound namely, acetyl acetone to obtain the corresponding hydrazono derivative (1). Cyclocondensation reaction of compounds (1) with hydrazine hydrate and phenyl hydrazine in boiling ethanol affording the corresponding pyrazoline-5-one derivatives of 4-aminobenzoic acid (2,3). Then compound (3) was reacted with thionyl chloride to give the corresponding acid chloride derivative(4), followed by conversion into the corresponding acid hydrazide derivative (5) carboxylic acid thiosemicarbazide (11), esters
... Show MoreThe efficiency evaluation of the railway lines performance is done through a set of indicators and criteria, the most important are transport density, the productivity of enrollee, passenger vehicle production, the productivity of freight wagon, and the productivity of locomotives. This study includes an attempt to calculate the most important of these indicators which transport density index from productivity during the four indicators, using artificial neural network technology. Two neural networks software are used in this study, (Simulnet) and (Neuframe), the results of second program has been adopted. Training results and test to the neural network data used in the study, which are obtained from the international in
... Show MoreResearch on the automated extraction of essential data from an electrocardiography (ECG) recording has been a significant topic for a long time. The main focus of digital processing processes is to measure fiducial points that determine the beginning and end of the P, QRS, and T waves based on their waveform properties. The presence of unavoidable noise during ECG data collection and inherent physiological differences among individuals make it challenging to accurately identify these reference points, resulting in suboptimal performance. This is done through several primary stages that rely on the idea of preliminary processing of the ECG electrical signal through a set of steps (preparing raw data and converting them into files tha
... Show MoreExtracorporeal Shock Wave Lithotripsy (ESWL) is the most commonplace remedy for kidney stone. Shock waves from outside the body frame are centered at a kidney stone inflicting the stone to fragment. The success of the (ESWL) treatment is based on some variables such as age, sex, stone quantity stone period and so on. Thus, the prediction the success of remedy by this method is so important for professionals to make a decision to continue using (ESWL) or tousing another remedy technique. In this study, a prediction system for (ESWL) treatment by used three techniques of mixing classifiers, which is Product Rule (PR), Neural Network (NN) and the proposed classifier called Nested Combined Classi
... Show MoreIn this paper the concept of (m, n)- fully stable Banach Algebra-module relative to ideal (F − (m, n) − S − B − A-module relative to ideal) is introducing, we study some properties of F − (m, n) − S − B − A-module relative to ideal and another characterization is given
This research was conduct to evaluate the cytotoxic effect of exotoxin A (ETA) produced by Pseudomonas aeruginosa on mice in comparison with (phosphate buffer saline (PBS) as a negative control. The effect of the toxin was measured by employing the cytogenetic analysis which included (the mitotic index (MI), chromosomal aberrations (CAs), micronucleus (MN) and sperm abnormalities) parameters. In order to specify the cytotoxic effect of the toxin, three doses of ETA (125, 250 and 500 ng/ml) were used. Results showed that ETA was found to cause a significant decrease in mitotic index (MI) percentage, while significant increase in micronucleus (MN), chromosomal aberrations (CAs) and sperm abnormalities parameters in compression with control wa
... Show MoreThe effects of temperature on an exotic aquatic snail Pomacea canaliculata (Lamarck, 1819) collected from the Shatt Al-Arab intertidal zone were investigated. A series of laboratory experiments were conducted during the summer period of 2017. Individuals of new born snails hatched in the laboratory from adult snails were collected from Shatt Al-Arab intertidal zone, and subjected to five fixed temperatures: 15, 25, 35, 40 and 45 Cº, after short term thermal acclimation. The heartbeats (HB) were counted at each temperature level. The results showed significant direct increase of HB from 15 Cº (19.8 HB/min) up to 25 Cº (76 HB/min) (P<0.05) as well as from 25 Cº to 35 Cº (93 HB/min). At 40 Cº the snail HB
... Show MoreZusammenfassung: Das Drama " Minna von Barnhelm von Lessing ist ein weltbekannts Drama, das in verschiedene Sprachen übersetzt wurde. Es beschreibt die Schwierigkeiten eines Offiziers, der bestraft wurde. Er verlor seinen Job und auch seine Ehre. Minna ist seine Verlobte, die ihn suchte und auch neben ihm stehen wollte. Trotzdem sie ihm in einem Hotel zufällig begegnete, hatten die beide immer noch Probleme. Am Ende des Dramas könnten sie alle ihrer Probleme lösen und hatten schönes Ende.
Abstract:
Mina von Barnhelm is a German play written by the author ( Lessing ) , it's a well-known comedy play that was translated into many languages including Arabic language .
This play is about a