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.
The phenomenon of spatial variation in the economic, social and urban development levels is considered prevalent in most of the economic and social systems,this relates to the concentration of most of those activities in certain regions and because of their rarity in other regions , that led to the emergence of the problem of the sharp contrast between the most developed areas and least developed areas within the same region or within the regions of the same country,
Reduction of this variables , in addition to the development of areas through following up and relying on an effective regional development enabling to reduce unemployment as well as to stop the migration of the unplanned for population,
And the ideal use of available
Background: Colorectal cancer (CRC) is a major killer, and nonalcoholic fatty liver disease (NAFLD) affects almost one-quarter of the global population. The aim of the study is to Investigate the correlation between nonalcoholic fatty liver disease (NAFLD) and an increased risk of colorectal cancer (CRC), as well as the relationship between liver function enzymes and specific serum biomarkers in CRC patients with NAFLD. Methods: A case-control study involving 60 participants was conducted from February to August 2022. The patients with colon cancer were examined at Baghdad Medical City's Al-Amal Hospital for Radiation and Nuclear Medicine and Oncology Teaching Hospital, and blood samples were taken. Thirty patients with NAFLD who ha
... Show MoreThe study is done in the period between (February 20 and October 20) by using ten adult quail Coturnix coturnix (Linnaeus, 1758). The sections are preparing by paraffin method then stain in Harris haematoxylin-eosin. The histological aspects of spinal cord in quail (Coturnix coturnix) the white matter is in the outer part, while the gray matter is arranged in from of X represents its internal part, the dorsal region is called the dorsal horns while the ventral region is called the ventral horns and the central canal cavity, the spinal cord areas appeared as follows: The medial column, column of von Lenhossek, lateral column, dorsal magnocellular column and marginal paragriseal, columns are also called Hoffmann’s nuclei.
This research was conducted to study the histological structure of the eye in the tree frog (Hyla arborea savignyi) and showed that it is composed of the eyeball and the lens and optic nerve. Appeared eyeball is surrounded by three Tunica from the inside to the outside are Tunica Interna, Tunica vasculosa, Tunica fibrosa. The tunica interna consists of the retina that consists of 10 layers are from outer to inner pigment epithelial layer, rods and cones layer, external limiting membrane, outer nuclear layer, outer plexiform layer, inner nuclear layer, inner plexiform layer , ganglion cells layer , nerve fibers layer, internal limiting membrane .The vascular tunic or Uvea consists of the choroid, ciliary body , and iris . The fibrous coat co
... Show MoreTheoretical trends have appeared Which posed the concept of biological structures in contemporary architecture concept, Spread through the emergence of architectural production that reflect and indicate the nature of the construction structures based on the ideas and principles of biological structures in biological science: Despite the emergence of many architectural proposals that tried to explain the concept in the field of architecture, but it is not dealt with in depth and not given a comprehensive definition: So there was need to search for the concept and its beginning in the biological field as a general framework down to the field of architecture for the purpose of reducing the limits of their search framework T
... Show MoreAbstract.. Quantitative characteristics of the surrounding world’s entities are expressed by the specific words – logical quantifiers. In a language, quantifiers are represented by the so-called quantifier words. Representing different degrees of the concentration of quantity, quantifier words in natural languages are positioned in a strict sequence – the quantifying scale. In terms of logic, it starts with nothingness (quantifier of meaningful nothingness), terminating at universality while in terms of language quantifier words, it is represented by the complex scale of quantifying words’ intensity. Logically speaking, this scale should start with the quantifier word ‘nothing’ to move all the way through increasing intensity ov
... Show MoreArid and semi-arid climates are critical for water security in sustainable river systems. The Euphrates River in western Iraq has been increasingly stressed by both geogenic and anthropogenic factors. This study analyzed hydro-geochemical processes, recharge dynamics, and groundwater flow modeling in western Iraq. Additionally, stable isotope tracing (δ¹⁸O, Cl⁻) integrated with hydro-chemical parameters was used to assess water quality and river-aquifer connectivity in both Syria and western Iraq. A total of 144 groundwater samples were collected annually across 12 stations in western Iraq. Surface water and groundwater data were collected from previous studies at 13 stations in Syria. Results revealed slightly alkaline freshwater con
... Show MoreCoupling reaction of 4-amino antipyrene with 4-amino benzoic acid gave bidentate azo ligand. The prepared ligand was identified by Microelemental Analysis, 1HNMR, FT-IR and UV-Vis spectroscopic techniques. Treatment of the prepared ligand with the following metal ions (CoII, NiII, CuII and ZnII) in aqueous ethanol with a 1:2 M:L ratio and at optimum pH, yielded a series of neutral complexes of the general formula [M(L)2]Cl2 . The prepared complexes were characterized using flame atomic absorption, (C.H.N) Analysis, FT-IR and UV-Vis spectroscopic methods as well as magnetic susceptibility and conductivity measurements. Chloride ion content was also evaluated by (Mohr method). The nature of the complexes formed were studied following the mol
... Show More2-amino-4-(4-chloro phenyl)-1,3-thiazole (1) was synthesized by refluxing thiourea with para-chloro phenacyl bromide in absolute methanol. The condensation of amine compound (1) with phenylisothiocyanate in the presence of pyridine will produce 1-(4-(4-chlorophenyl)thiazol-2-yl)-3-phenylthiourea(2), which is upon treatment with 2,4 dinitrophenyl hydrazine by conventional method, afforded 1- ( 4 - ( 4 – chlorophenyl ) thiazol – 2 – yl ) – 3 - phenylhydrazonamide,N' - ( 2 , 4 -dinitrophenyl) ,(3).The characterization of the titled compounds were performed utilizing FTIR spectroscopy, 1HNMR and CHNS elemental analysis, and by me
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