Dipeptidyl peptidase-4 DPP-4 inhibition has remained one of the most established ways in treating type 2 diabetes mellitus. Therefore, the development of improved DPP-4 inhibiters is consideredan essential strategy in the design of antidiabetic drugs. In the present study, a structure-based virtual approach was considered to design and evaluate new sitagliptin analogues with improved binding stability and pharmacokinetic properties. A virtual library consisting of 15,034 different compounds was created and then screened using a hierarchical Glide docking protocol (HTVS, SP, and XP). Using integrated computational analyses, the top ranked compounds were further assessed. Based on ADMET predictions, MM-GBSA binding free energy calculations, the results revealed that out of all the screened compounds, only 28 candidates had better docking scores than sitagliptin and compounds 14 and 22 were the most promising screened analogues. Compared to other tested analogies, compound 14 showed stable binding profile,low MM-GBSA binding free energy,stable ionic interactions between the catalytic residues Glu205 and Glu206, stable hydrophobic interactions within the S1 pocket. In addition, based on ADME simulation, compound 14 presented acceptable drug-like properties which indicates good oral bioavailability and lower predicted CNS penetration compared to sitagliptin. Overall, further experimental validation and development is required to evaluate compound 14 which exhibitsan increased electrostatic complementarity, dynamically stable properties, and acceptable pharmacokinetic properties making it a promising candidate as a DPP-4 inhibitor.
This research discusses the subject of identity in the urban environment as it attempts to answer a number of questions that come with the concept of identity. The first of these questions: What is identity? Can a definition or conceptual framework be developed for identity? What about individual, collective, cultural, ethnic, political and regional identity? Is there a definition of identity in the urban environment in particular? If there is a definition of identity, what about social mobility responsible for social change? How can we see identity through this kinetics? Can we assume that identity in the urban environment has a variable structure or is of variable shape with a more stable structure? Can we determine the spatial-tempora
... Show MoreThe two body model of (Core+n) within the radial wave functions of the cosh potential has been used to investigate the ground state features such as the proton, neutron and matter densities, the root mean square (RMS) nuclear proton, neutron, charge and mass radii of unstable neutron-rich 14B, 15C, 19C and 22N nuclei. The calculated results show that the two body model with the radial wave functions of the cosh potential succeeds in reproducing neutron halo in these nuclei.
A new azo (LH) ligand was prepared by coupling reaction between, diazonium salt of Sulfamethoxazole, and 8-hydroxyquinoline in a process called diazotization process resulting in azo-ligand [4-((8-hydroxyquinolin-7-yl)- N(4-methylisoxazol-3-yl) benzene sulfonamide]. The azo ligand was identified by using spectroscopic techniques to detect and characterize the formation of ligand and complexes of Ni2+, Pt4+, Pd2+, and Rh3+ metal ions, and to determine the chelating behavior of ligand and also its bind position. All complexes have a [1:1] [M-ligand] ratio and all complexes are nonelectrolytes and most of the complexes have octahedral geometry, while Pd2+complex gave square planer geometry and Ni2+ complex indicate tetrahedral geometry. Therma
... Show MoreBacterial toxins are considered to be virulence factors due to the fact that they interfere with the normal processes of the host cell in which they are found. The interplay between the infectious processes of bacteria and the immune system is what causes this impact. In this discussion, we are going to focus on bacterial toxins that act in the extracellular environment, especially on those that impair the activity of macrophages and neutrophils. These toxins are of particular interest since they may be found in a wide variety of bacteria. We will be concentrating our efforts, in particular, on the toxins that are generated by Gram-positive and Gram-negative bacteria. These toxins are able to interact with and have an effect on the many dif
... Show MoreActive worms have posed a major security threat to the Internet, and many research efforts have focused on them. This paper is interested in internet worm that spreads via TCP, which accounts for the majority of internet traffic. It presents an approach that use a hybrid solution between two detection algorithms: behavior base detection and signature base detection to have the features of each of them. The aim of this study is to have a good solution of detecting worm and stealthy worm with the feature of the speed. This proposal was designed in distributed collaborative scheme based on the small-world network model to effectively improve the system performance.
The liver is the primary organ for drug metabolism, elimination, Cyclophosphamid is the classical alkylating agent nitrogen mustard, its metabolism into two cytotoxic metabolites, and increase reactive oxygen species that is make liver toxicity. Safranal as the most abundant chemical in saffron essential oil, it have anti-oxidant, anti-inflammatory, antiapoptic and free radical scavenger activity. The aim of study is to assess the protective effects of safranal on the cyclophosphamide-induce liver toxicity in rat model. This occur by using five different groups of rats; control group, treatment group, cyclophosamide group (intraperitoneal i.p), cyclophosamide and (50mg and 100mg) oral safranal treatment groups. This study showed this pro
... Show MoreRed cabbage and garlic extracts have protective effect against liver damage induced by fumonisin B1 (FB1) in male mice was studied. Randomly sixty mice have been divided in to six groups. Group one are the healthy mice, Group two are mice received oral dose of only FB-1 (100 μg/kg.b.w) once on daily for 1 month, Group three: mice received with red cabbage extract (500 mg/kg.bw) plus FB1, Group four: mice receiving just red cabbage extracts, Group five: mice receiving garlic extract (500mg/kg.bw) plus FB1, group 6: mice received only garlic extract. After finished the experiment, samples of blood were used for biochemical examination. The results indicated that group (2) mice treated
The current trend worldwide is searching plant extracts towards prevention of neurodegenerative disorders. This study aimed to investigate the neuroprotective effect of Alpinia galanga leaves (ALE), Alpinia galanga rhizomes (ARE), Vitis vinifera seeds (VSE), Moringa oleifera leaves (MLE), Panax ginseng leaves (PLE) and Panax ginseng rhizomes (PRE) ethanolic extracts on human neuroblastoma (SHSY5Y) cells. The 1‐diphenyl‐1‐picrylhydrazyl (DPPH) radical scavenging of VSE and MLE were 81% and 58%, respectively. Ferric‐reducing antioxidant power (FRAP) of ALE and MLE (33.57 ± 0.20 and 26.76 ± 0.30 μmol Fe(ΙΙ)/g dry wt., respectively) were higher than for the other extracts. Liquid chromatography coupled to quadrupole time‐of‐fli
... Show MoreThe current study aimed to assess the biological efficacy of the triple arbuscular mycorrhiza (AM) mixture of fungi Glomus etunicatum, G. leptotichum and Rhizophagus intraradices, and mix it with organic matter (O) and pathogenic fungi Fusarium oxysporum f.sp.lycopersici by using voyeurism in the plastic house in the growth of the tomato plant after four and eight weeks of cultivation. The results were shown after the treatment of the tomato plant in agriculture with the mixture of mycorrhiza and the pathogenic fungi and organic matter were treated with the mixture of mycorrhiza, organic matter and pathogenic fungi together. The effect of mycorrhiza and organic matter interference on the increase in the percentage of the lignin afte
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