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并研究双(吲哚-3-基)甲烷衍生物作为潜在的α-葡萄糖苷酶和α-淀粉酶抑制剂。

and studies of bis (indol-3-yl) methane derivatives as potential α-glucosidase and α-amylase inhibitors.

机构信息

Second Hospital of Lanzhou University, Lanzhou, PR China.

School of Biotechnology and Health Sciences, Wuyi University, Jiangmen, PR China.

出版信息

J Enzyme Inhib Med Chem. 2021 Dec;36(1):1938-1951. doi: 10.1080/14756366.2021.1971976.

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 (IC: 7.54 ± 1.10 μM), (IC: 9.00 ± 0.97 μM), and (IC: 9.57 ± 0.62 μM) presented strongest inhibitory activities against α-glucosidase, that were ∼ 30 times stronger than acarbose. Compounds (IC: 32.18 ± 1.66 µM), (IC: 31.47 ± 1.42 µM), and (IC: 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 and exhibited bifunctional inhibitory activity against these two enzymes. Furthermore, compounds showed no toxicity against 3T3-L1 cells and HepG2 cells.HighlightsA series of bis (indol-3-yl) methanes (BIMs) were synthesised and evaluated inhibitory activities against -glucosidase and α-amylase.Compound exhibited promising activity (IC = 7.54 ± 1.10 μM) against -glucosidase.Compound exhibited promising activity (IC = 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.

摘要

本文合成了双(吲哚-3-基)甲烷(BIMs),并评价了它们对α-葡萄糖苷酶和α-淀粉酶的抑制活性。所有合成的化合物均表现出潜在的α-葡萄糖苷酶和α-淀粉酶抑制活性。化合物(IC:7.54±1.10μM)、(IC:9.00±0.97μM)和(IC:9.57±0.62μM)对α-葡萄糖苷酶表现出最强的抑制活性,比阿卡波糖强约 30 倍。化合物(IC:32.18±1.66μM)、(IC:31.47±1.42μM)和(IC:30.91±0.86μM)对α-淀粉酶表现出最强的抑制活性,比阿卡波糖强约 2.5 倍。还研究了这些化合物的作用机制和对接模拟。化合物和表现出对这两种酶的双功能抑制活性。此外,化合物对 3T3-L1 细胞和 HepG2 细胞没有毒性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ea21/8409970/13b80985f24d/IENZ_A_1971976_UF0001_C.jpg

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