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 histological structure of integument in Mastacembelus mastacembelus have been investigated from skin fragments cut from nine regions at body surface. The results revealed that the integument of the fish investigated comprises three principal layers- the epidermis, the dermis (corium) and the subcutis-All the three principal layers may further be divided into secondary layers according to the function performed by their cells. The epidermis may further divided into three layers- the outermost epithelial coverage, the middle layer and the basal layer (stratum germinatiuum)-The dermis consists of a relatively thin upper layer of loose vascular connective tissue called the stratum laxum and a thick lower compact layer- the stratum compactu
... Show MoreThis research attempts to investigate narrative structure in oral narrative particularly in Oprah's Show from a sociolinguistic viewpoint. Narrative is said to be universal in the sense that it is found in all times and places. There is no society or culture without narrative. Oral narrative is organized in a specific order. The research aims at studying and analyzing this order. In addition to that, it highlights the importance of narrative in conveying some moral messages to people who are listening to the story. The study is divided into two parts; theoretical and practical. The theoretical part draws on presenting a survey of literature which includes definitions and explanations of some related terms. The practical part is concerned
... Show MoreThe aim of the present study was to investigate the histological structure of the tongue in Mongoose (Herpestes javanicus) and its related to the feeding pattern. Five adult animals were used in this study . The tongues were dissected and fixed in 10% formalin, then prepared by following stages (dehydration, clearing, and embedding).The serial section(5µ) were stained with(H&E) and some special stains.The histological examination showed that the tongue consists of three tunicae (mucosa, submucosa and musclaris) and the lining epithelium of the filiform papillae is composed of keratinized stratified squamous epithelial tissue. The cylindrical papillae are covered with a highly keratinized stratified squamous epithelial tissue, whereas the k
... Show MoreThe structure is considered in its scientific formula one of the concepts which complete the architectural image that seeks to take out an effective and attractive structure in contemporary architectural production, especially that the structure -in general- represents strength in addition to delight and functional benefits according to Vitruvius trinity. So, the role of structure depends on making its aesthetical properties able to give efficiency within architectural product. That has come through adoption of intellectual mechanism of structural means and details –as a whole or parts- and focused on structure with the recipient's needs, aesthetical, and sensory purposes in addition to its fundamental role of stabilit
... Show More Educational services in Iraq face many problems that have reduced the efficiency of the educational process, as a result of the difficult conditions experienced by educational services in Iraq. This led to the accumulation of these problems and their exacerbation significantly over the years, as there was no fundamental solution to these problems. The study proposes a planning method for managing the educational system in Iraq, especially for the primary and secondary levels, where these negative phenomena are very prominent, especially the deficit in school buildings and the phenomenon of overcrowding in classrooms. &am
... Show MoreTwo series of Schiff Bases [VI]n and thiazolidin-4-one derivatives[VII]n were synthesized by many steps starting from cyclization of 4- hydroxyacetophenon with thiourea in iodine to yield 1,3-thiazole compound which was reacted with pentoxy bromide in anhydrous potassium carbonate to converted compound[II] and this reacted with Phenol to yield azo compound[III]. The azo compound reacted with ethyl chloro acetate in basic medium to get a new easter compound[IV] which is converted to their acid hydrazid[V]. The later compound condensation with n-alkoxy benzaldehyde to give new Schiff bases[VI]n . Imine group undergoes addition cyclization with thioglycolic acid to get thiazolidinone compounds[VII]n .Also, two new series of Schiff Bases [XII]n
... Show MoreCrimes are prohibited by law and God Almighty has forbidden them with punishment or punishment.
The punishment is the prescribed punishments that the law has determined in its place and stipulated in the Book of God or the Sunnah of His Prophet, may God bless him and grant him peace.
Ta’zir: These are the punishments that are left to the ruler to assess according to what he sees as preventing corruption on earth and preventing evil. Extrapolation has proven that all the provisions of Islamic Sharia include the interests of the people, and they are based on five matters: what is in it is preserving the religion, what is in it is preserving the soul, and what is in it is preserving the soul. It involves preserving the mind, preserv
Design system often generated relationship within the frame work of their concept of interior design a system or more can be created between design relationships within this concept in the structure of its internal space product. Through the division of all to it parts to reveal the hidden places and stages of composition and their relationship and interdependence between them. And then re- composition of all its parts, doth in the deign process at the initial stages or in the processes of treatments that are necessary after the completion of design and circulation. To be able to use other events close to the first events designed for them. In terms of idea logical in fluency and its social, economic, cultural and political dimension. As
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