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Title
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Docking study, molecular dynamic, synthesis, anti-α-glucosidase assessment, and ADMET prediction of new benzimidazole-Schiff base derivatives
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Type
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JournalPaper
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Keywords
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Docking study, ADMET prediction, benzimidazole, Schiff base derivatives
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Abstract
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The control of postprandial hyperglycemia is an important target in the treatment of type 2 diabetes mellitus (T2DM). As a result, targeting α-glucosidase as the most important enzyme in the breakdown of carbohydrates to glucose that leads to an increase in postprandial hyperglycemia is one of the treatment processes of T2DM. In the present work, a new class of benzimidazole-Schiff base hybrids 8a–p has been developed based on the potent reported α-glucosidase inhibitors. These compounds were synthesized by sample recantations, characterized by 1H-NMR, 13C-NMR, FT-IR, and CHNS elemental analysis, and evaluated against α-glucosidase. All new compounds, with the exception of inactive compound 8g, showed excellent inhibitory activities (60.1 ± 3.6–287.1 ± 7.4 µM) in comparison to acarbose as the positive control (750.0 ± 10.5). Kinetic study of the most potent compound 8p showed a competitive type of inhibition (Ki value = 60 µM). In silico induced fit docking and molecular dynamics studies were performed to further investigate the interaction, orientation, and conformation of the title new compounds over the active site of α-glucosidase. In silico druglikeness analysis and ADMET prediction of the most potent compounds demonstrated that these compounds were druglikeness and had satisfactory ADMET profile.
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Researchers
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Maryam Mohammadi-Khanaposhtani (Not In First Six Researchers), Yaghoub Sarrafi (Not In First Six Researchers), mohammad mahdavi (Not In First Six Researchers), Hossein Rastegar (Not In First Six Researchers), Bagher Larijani (Not In First Six Researchers), Hossein Adibi (Not In First Six Researchers), Samanesadat Hosseini (Not In First Six Researchers), Mohammad Ali Faramarzi (Not In First Six Researchers), Ali Zamani (Not In First Six Researchers), Kimia Khavaninzadeh (Fifth Researcher), Yousef Valizadeh (Fourth Researcher), Ali Moazzam (Third Researcher), Keyvan Pedrood (Second Researcher), Homa Azizian (First Researcher)
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