Title:In vitro α-Glucosidase Inhibition by Non-sugar based Triazoles of Dibenzoazepine, their Structure-Activity Relationship, and Molecular Docking
Volume: 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
Affiliation:
- H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270,Pakistan
Keywords:
Acetophenones, diabetes, dibenzoazepine, molecular docking, triazoles, α-glucosidase.
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.
