Discovery of natural anthraquinones as potent inhibitors against pancreatic lipase: structure-activity relationships and inhibitory mechanism

• Published in: Journal of enzyme inhibition and medicinal chemistry Vol. 39; no. 1; p. 2398561
• Main Authors: Chen, Zi-Qiang, He, Wen-Yao, Yang, Si-Yuan, Ma, Hong-Hong, Zhou, Jing, Li, Hao, Zhu, Ya-Di, Qian, Xing-Kai, Zou, Li-Wei
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis 01.12.2024; Taylor & Francis Group
• Subjects: anthraquinones; Anthraquinones - chemical synthesis; Anthraquinones - chemistry; Anthraquinones - pharmacology; Biological Products - chemical synthesis; Biological Products - chemistry; Biological Products - pharmacology; Dose-Response Relationship, Drug; Drug Discovery; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - chemistry; Enzyme Inhibitors - pharmacology; Humans; inhibitor; Lipase - antagonists & inhibitors; Lipase - metabolism; Molecular Docking Simulation; Molecular Structure; Pancreas - enzymology; Pancreatic lipase; Structure-Activity Relationship; structure-activity relationships; Pancreatic lipase; anthraquinones; inhibitor; structure-activity relationships
• ISSN: 1475-6366; 1475-6374; 1475-6374
• DOI: 10.1080/14756366.2024.2398561

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.