In vitro and in silico studies of bis (indol-3-yl) methane derivatives as potential α-glucosidase and α-amylase inhibitors

Abstract

In this paper, bis (indol-3-yl) methanes (BIMs) were synthesised and evaluated for their inhibitory activity against α-glucosidase and α-amylase. All synthesised compounds showed potential α-glucosidase and α-amylase inhibitory activities. Compounds 5 g (IC 50 : 7.54 ± 1.10 μM), 5e (IC 50 : 9.00 ± 0.97 μM), and 5 h (IC 50 : 9.57 ± 0.62 μM) presented strongest inhibitory activities against α-glucosidase, that were ∼ 30 times stronger than acarbose. Compounds 5 g (IC 50 : 32.18 ± 1.66 µM), 5 h (IC 50 : 31.47 ± 1.42 µM), and 5 s (IC 50 : 30.91 ± 0.86 µM) showed strongest inhibitory activities towards α-amylase, ∼ 2.5 times stronger than acarbose. The mechanisms and docking simulation of the compounds were also studied. Compounds 5 g and 5 h exhibited bifunctional inhibitory activity against these two enzymes. Furthermore, compounds showed no toxicity against 3T3-L1 cells and HepG2 cells. Highlights A series of bis (indol-3-yl) methanes (BIMs) were synthesised and evaluated inhibitory activities against α -glucosidase and α-amylase. Compound 5g exhibited promising activity (IC 50 = 7.54 ± 1.10 μM) against α -glucosidase. Compound 5s exhibited promising activity (IC 50 = 30.91 ± 0.86 μM) against α-amylase. In silico studies were performed to confirm the binding interactions of synthetic compounds with the enzyme active site.

Synthesis of Benzylidene Analogs of Oleanolic Acid as Potential α-Glucosidase and α-Amylase Inhibitors

“…Molecular docking was performed using SYBYL software to investigate the interaction between inhibitors and target protein ( Zheng P.-F. et al, 2021 ; Hu, et al, 2021 ). The crystal structure of Saccharomyces cerevisiae α -glucosidase was not resolved so far.…”

Anti-α-Glucosidase, SAR Analysis, and Mechanism Investigation of Indolo[1,2-b]isoquinoline Derivatives

“…The α-glucosidase inhibitory activity of indole [1,2-b]isoquinoline derivatives (1-20) was determined using PNPG as a substrate according to previous reports [34][35][36]. α-Glucosidase (0.1 U/mL) and the test compound were added to phosphate-buffered saline (0.1 M, pH 6.8) and then incubated for 10 min at 37 • C. After the addition of PNPG (0.25 mM), the change in absorbance was measured at 405 nm.…”

Ubiquitin‐conjugating enzyme E2 for regulating autophagy in diabetic cardiomyopathy: A mini‐review

“…Diabetes mellitus (DM) is one of the most common chronic systemic diseases, 1 the prevalence of which is increasing year by year due to increasing life expectancy and changes in diet and daily habits. 2 Diabetic cardiomyopathy (DCM) is one of the most serious cardiovascular complications of DM, 3 and the prevalence of DCM has increased in recent years along with the increasing prevalence of obesity and DM.…”