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.
Isradipine related to dihydropyridine (DHP) class of calcium channel blockers (CCBs). It is used to treat hypertension, angina pectoris, as well as Parkinson disease. It goes under the BCS class II drug (low solubility-high permeability). The drug will experience extensive first-pass metabolism in liver, thus, oral bio-availability will be approximately15 to 24 %.
The aim of the study is preparing stable oral oil in water (o/w) nanoemulsion of isradipine to promote the colloidial dispersion of isradipine in the nano range, so that it may be absorded by intestinal lymphatic transport in order to avoid hepatic first-pass metabolism (israpidi
... Show MoreSome new 2,5-disubsituted-1,3,4-oxadiazole derivatives with azo group were synthesized by known reactions sequence . The structure of the synthesized compounds were confirmed by physical and spectral means .
In this work 2-hydrazino pyrimidine (1) was prepared from 2-mercapto pyrimidine with hydrazine hydrate. Treatment of (1) with active methylene compounds gave 2-(3,5-dimethyl -1 H – Pyrazole-1-yl) pyrimidine , whereas the reaction of (1) with carboxylic anhydride namely maleic anhydride or 1,2,3,6-tetra hydro phthalic anhydride yielded 1-Pyrimidine-2-yl-1,2-dihydro pyridazine-3,6-dione (3) and 2 – Pyrimidin -2-yl -2,3,4 a ,5,8 a – hexahydro phthalazine 1,4 – dione (4) . Reaction of (1) with phenyl isothiocyanate and ethyl chloro acetate afforded 3-Phenyl-1,3-thiazolidine-2,4-dione-2( pyrimidine -2- yl hydrazone (6) Azomethine (7-10) were prepared through condensation of (1) with aromatic aldehydes or ketones, then comp
... Show MoreNew series of 2-mecapto benzoxazole derivatives (1-20) incorporated into fused to different nitrogen and suphur containing heterocyclic were prepared from 2-meracpto benzoxazole, when treated with hydrazine hydrate to afford 2-hydrazino benzoxazol (1). Compound (1) converted to a variety of pyridazinone andphthalazinone derivatives (2-4) by reaction with different carboxylic anhydride. Also, reaction of (1) with phenyl isothiocyanate and ethyl chloro acetate afforded 3-phenyl-1,3-thiazolidin-2,4-dione-2-(benzoxazole-2-yl-hydrazone) (6). Azomethines (7-10) were prepared through reaction of (1) with aromatic aldehyde, then (7, 8) converted to thaizolidinone derivatives (11, 12). Treatment of (1) with active methylene compounds afforded deriva
... Show MoreThe thermoelectric power as a function of temperature for the Iron-Manganese-Aluminum, Fe-Mn-Al, alloys for manganese concentrations 0.04, 0.06, 0.08, 0.10 and 0.20 have been investigated in the temperature range 300 K. to 500 K. these results showed that the thermoelectric power coefficient in hot probe measurements showed that the electrons are the majority charge carriers in these alloys.
This research involves design and simulation of GaussianFSK transmitter in UHF band using direct modulation of ΣΔ fractional-N synthesizer with the following specifications:
Frequency range (869.9– 900.4) MHz, data rate 150kbps, channel spacing (500 kHz), Switching time 1 µs, & phase noise @10 kHz = -85dBc.
New circuit techniques have been sought to allow increased integration of radio transmitters and receivers, along with new radio architectures that take advantage of such techniques. Characteristics such as low power operation, small size, and low cost have become the dominant design criteria by which these systems are judged.
A direct modulation by ΣΔ fractional-N synthesizer is proposed
... Show MoreA preventing shield for neutrons and gamma rays was designed using alternate layers of water and iron with pre-fixed dimensions in order to study the possibility of attenuating both neutrons and gamma-rays. ANISN CODE was prepared and adapted for the shield calculation using radiation doses calculation: Two groups of cross-section were used for each of neutrons and gamma-rays that rely on the one – dimensional transport equation using discrete ordinate's method, and through transforming cross-section values to values that are independent on the number of groups. The memory size required for the applied code was reduced and the results obtained were in agreement with those of standard acceptable document samples of cross –section, this a
... Show MoreThis research deals with the topic (Fantasy Parody in the Design of the Advertisement) in view of the important role that fantasia plays in designing the most creative and attractive advertisements to the recipients. The research problem lies in accordance with the following question:
What is the Fantasy Parody in the Design of the Advertisement?
It means the imagination, the unfamiliar; and features that emerge for it that distinguish it from other concepts. Fantasy advertisement is creativity in innovative ways, either through collage, merging, or the use of various artistic expressions in terms of intellectual and cultural awareness. When uses in the parody of advertisement, it has helped to come up with an aesthetic experie
The visual stimulus is the effective force in visual attraction that achieves visual and perceptual co-optation and is important in wooing the recipient, and many procedural processes in the design are interpreted on it as the visual stimulus achieves visual comfort and a sense of pleasure and gives (place) the interior space a transformation in its plastic structure as well as arousing attention through The kinetic rhythm and the formal diversity, which increases the possibility of breaking the routine and traditional constraints of design patterns through the coating and encapsulation of the vertical and horizontal levels . Thus, the research problem was launched based on the following question: What are the stimuli of the visual stimu
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