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In vitro α-Glucosidase Inhibition by Non-sugar based Triazoles of Dibenzoazepine, their Structure-Activity Relationship, and Molecular Docking

[ Vol. 13 , Issue. 7 ]

Author(s):

Maria A. Khan*, Kulsoom Javaid, Abdul Wadood, Alam Jamal, Farhana Batool, Saba Fazal-ur-Rehman, Fatima Z. Basha and Muhammad I. Choudhary   Pages 698 - 704 ( 7 )

Abstract:


Background: α-Glucosidase inhibitors (AGIs) have been reported for their clinical potential against postprandial hyperglycemia, which is responsible for the risks associated with diabetes mellitus 2 and cardiovascular diseases (CVDs). Besides, a number of compounds have been reported as potent AGIs, several side effects are associated with them.

Methods: The aim of present work is to explore new and potent molecules as AGIs. Therefore, a library of dibenzoazepine linked triazoles (1-15) was studied for their in vitro α-glucosidase inhibitory activity. The binding modes of potent compounds in the active site of α-glucosidase enzyme were also explored through molecular docking studies.

Results and Conclusion: Among the reported triazoles, compounds 3-9, 11, and 13 (IC50 = 6.0 ± 0.03 to 19.8 ± 0.28 µM) were found to be several fold more active than the standard drug acarbose (IC50 = 840 ± 1.73 µM). Compound 5 (IC50 = 6.0 ± 0.03 µM) was the most potent AGIs in the series, about 77- fold more active than acarbose. Therefore, dibenzoazepine linked-triazoles described here can serve as leads for further studies as new non-sugar AGIs.

Keywords:

Acetophenones, diabetes, dibenzoazepine, molecular docking, triazoles, α-glucosidase.

Affiliation:

H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Department of Biochemistry, Computational Medicinal Chemistry Laboratory, UCSS, Abdul Wali Khan University Mardan, Department of Biochemistry, Computational Medicinal Chemistry Laboratory, UCSS, Abdul Wali Khan University Mardan, H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Department of Chemistry, University of Karachi, Karachi-75270, H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270

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