Design, synthesis and α-glucosidase inhibition study of novel embelin derivatives

Autor: Xiaole Chen, Min Gao, Rongchao Jian, Weiqian David Hong, Xiaowen Tang, Yuling Li, Denggao Zhao, Kun Zhang, Wenhua Chen, Xi Zheng, Zhaojun Sheng, Panpan Wu
Jazyk: angličtina
Rok vydání: 2020
Předmět:
Zdroj: Journal of Enzyme Inhibition and Medicinal Chemistry, Vol 35, Iss 1, Pp 565-573 (2020)
Druh dokumentu: article
ISSN: 1475-6366
1475-6374
14756366
DOI: 10.1080/14756366.2020.1715386
Popis: Embelin is a naturally occurring para-benzoquinone isolated from Embelia ribes (Burm. f.) of the Myrsinaceae family. It was first discovered to have potent inhibitory activity (IC50 = 4.2 μM) against α-glucosidase in this study. Then, four series of novel embelin derivatives were designed, prepared and evaluated in α-glucosidase inhibition assays. The results show that most of the embelin derivatives synthesised are effective α-glucosidase inhibitors, with IC50 values at the micromolar level, especially 10d, 12d, and 15d, the IC50 values of which are 1.8, 3.3, and 3.6 μM, respectively. Structure–activity relationship (SAR) studies suggest that hydroxyl groups in the 2/5-position of para-benzoquinone are very important, and long-chain substituents in the 3-position are highly preferred. Moreover, the inhibition mechanism and kinetics studies reveal that all of 10d, 12d, 15d, and embelin are reversible and mixed-type inhibitors. Furthermore, docking experiments were carried out to study the interactions between 10d and 15d with α-glucosidase.
Databáze: Directory of Open Access Journals
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