Synthesis of benzotriazoles derivatives and their dual potential as α-amylase and α-glucosidase inhibitors in vitro: Structure-activity relationship, molecular docking, and kinetic studies

Benzotriazoles (4-6) were synthesized which were further reacted with different substituted benzoic acids and phenacyl bromides to synthesize benzotriazole derivatives (7-40). The synthetic compounds (7-40) were characterized via different spectroscopic techniques including EI-MS, HREI-MS, H-1-, and C-13 NMR. These molecules were examined for their anti-hyperglycemic potential hence were evaluated for alpha-glucosidase and alpha-amylase inhibitory activities. All benzotriazoles displayed moderate to good inhibitory activity in the range of IC50 values of 2.00-5.6 and 2.04-5.72 mu M against alpha-glucosidase and alpha-amylase enzymes, respectively. The synthetic compounds were divided into two categories A and B, in order to understand the structure-activity relationship. Compounds 25 (IC50 = 2.41 +/- 131 mu M), (IC50 = 2.5 +/- 1.21 mu M), 36 (IC50= 2.12 +/- 1.35 M), (IC50 = 2.21 +/- 1.08 mu M), and 37 (IC50 = 2.00 +/- 1.22 mu M), (IC50 = 2.04 +/- 1.4 mu M) with chloro substitution/s at aryl ring were found to be most active against alpha-glucosidase and alpha-amylase enzymes. Molecular docking studies on all compounds were performed which revealed that chloro substitutions are playing a pivotal role in the binding interactions. The enzyme inhibition mode was also studied and the kinetic studies revealed that the synthetic molecules have shown competitive mode of inhibition against alpha-amylase and non-competitive mode of inhibition against alpha-glucosidase enzyme. (C) 2019 Elsevier Masson SAS. All rights reserved.