发现可作为胰脂肪酶强效抑制剂的天然蒽醌类化合物:结构-活性关系和抑制机制。

IF 5.6 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Zi-Qiang Chen, Wen-Yao He, Si-Yuan Yang, Hong-Hong Ma, Jing Zhou, Hao Li, Ya-Di Zhu, Xing-Kai Qian, Li-Wei Zou
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引用次数: 0

摘要

肥胖被认为是各种代谢性疾病的重要危险因素,而抑制人胰脂肪酶(hPL)可以阻碍脂质的消化和吸收,从而为肥胖症的治疗提供潜在的益处。蒽醌类化合物是一种应用广泛的天然及合成化合物。本研究评估了 31 种蒽醌类化合物对 hPL 的抑制作用。数据显示,AQ7、AQ26 和 AQ27 对 hPL 具有显著的抑制活性,并对其他已知的丝氨酸水解酶具有选择性。然后进一步分析了蒽醌类化合物与 hPL 之间的结构-活性关系。通过抑制动力学发现,AQ7 对 hPL 具有混合抑制作用,而 AQ26 和 AQ27 则对 hPL 具有有效的非竞争性抑制作用。分子对接数据显示,AQ7、AQ26 和 AQ27 都能与 hPL 的位点结合。有了这种新颖而有前景的先导化合物,开发用于肥胖症预防和治疗的 hPL 抑制剂就变得简单易行了。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Discovery of natural anthraquinones as potent inhibitors against pancreatic lipase: structure-activity relationships and inhibitory mechanism.

Obesity is acknowledged as a significant risk factor for various metabolic diseases, and the inhibition of human pancreatic lipase (hPL) can impede lipid digestion and absorption, thereby offering potential benefits for obesity treatment. Anthraquinones is a kind of natural and synthetic compounds with wide application. In this study, the inhibitory effects of 31 anthraquinones on hPL were evaluated. The data shows that AQ7, AQ26, and AQ27 demonstrated significant inhibitory activity against hPL, and exhibited selectivity towards other known serine hydrolases. Then the structure-activity relationship between anthraquinones and hPL was further analysed. AQ7 was found to be a mixed inhibition of hPL through inhibition kinetics, while AQ26 and AQ27 were effective non-competitive inhibition of hPL. Molecular docking data revealed that AQ7, AQ26, and AQ27 all could associate with the site of hPL. Developing hPL inhibitors for obesity prevention and treatment could be simplified with this novel and promising lead compound.

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来源期刊
CiteScore
10.30
自引率
10.70%
发文量
195
审稿时长
4-8 weeks
期刊介绍: Journal of Enzyme Inhibition and Medicinal Chemistry publishes open access research on enzyme inhibitors, inhibitory processes, and agonist/antagonist receptor interactions in the development of medicinal and anti-cancer agents. Journal of Enzyme Inhibition and Medicinal Chemistry aims to provide an international and interdisciplinary platform for the latest findings in enzyme inhibition research. The journal’s focus includes current developments in: Enzymology; Cell biology; Chemical biology; Microbiology; Physiology; Pharmacology leading to drug design; Molecular recognition processes; Distribution and metabolism of biologically active compounds.
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