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

• Main Authors: Peng-Fei Zheng (Author), Zhuang Xiong (Author), Cui-ying Liao (Author), Xin Zhang (Author), Mei Feng (Author), Xiao-Zheng Wu (Author), Jing Lin (Author), Lin-Sheng Lei (Author), You-Cheng Zhang (Author), Shao-Hua Wang (Author), Xue-Tao Xu (Author)
• Format: Book
• Published: Taylor & Francis Group, 2021-01-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 1475-6366; 1475-6374; 10.1080/14756366.2021.1971976
• Keywords: bis (indol-3-yl) methanes; α-glucosidase; α-amylase; inhibitor; molecular docking; Therapeutics. Pharmacology; RM1-950
• Source: Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 36, Iss 1, Pp 1938-1951 (2021)

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 (IC50: 7.54 ± 1.10 μM), 5e (IC50: 9.00 ± 0.97 μM), and 5 h (IC50: 9.57 ± 0.62 μM) presented strongest inhibitory activities against α-glucosidase, that were ∼ 30 times stronger than acarbose. Compounds 5 g (IC50: 32.18 ± 1.66 µM), 5 h (IC50: 31.47 ± 1.42 µM), and 5 s (IC50: 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 (IC50 = 7.54 ± 1.10 μM) against α-glucosidase. Compound 5s exhibited promising activity (IC50 = 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.