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 w...
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2024-12-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
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| Online Access: | https://www.tandfonline.com/doi/10.1080/14756366.2024.2398561 |
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| author | 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 |
| author_facet | 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 |
| author_sort | Zi-Qiang Chen |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-6c3dd1b0a8d343bfbdecfd4f902cc30f |
| institution | Kabale University |
| issn | 1475-6366 1475-6374 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj-art-6c3dd1b0a8d343bfbdecfd4f902cc30f2024-12-26T09:30:44ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742024-12-0139110.1080/14756366.2024.2398561Discovery of natural anthraquinones as potent inhibitors against pancreatic lipase: structure-activity relationships and inhibitory mechanismZi-Qiang Chen0Wen-Yao He1Si-Yuan Yang2Hong-Hong Ma3Jing Zhou4Hao Li5Ya-Di Zhu6Xing-Kai Qian7Li-Wei Zou8Translational Medicine Research Center, Guizhou Medical University, Guiyang, Guizhou, ChinaInstitute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaDepartment of Cardiac Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang, Guizhou, ChinaSchool of Basic Medicine, Guizhou Medical University, Guiyang, Guizhou, ChinaTranslational Medicine Research Center, Guizhou Medical University, Guiyang, Guizhou, ChinaInstitute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaSchool of Basic Medicine, Guizhou Medical University, Guiyang, Guizhou, ChinaTranslational Medicine Research Center, Guizhou Medical University, Guiyang, Guizhou, ChinaInstitute of Interdisciplinary Integrative Medicine Research, Shanghai University of Traditional Chinese Medicine, Shanghai, ChinaObesity 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.https://www.tandfonline.com/doi/10.1080/14756366.2024.2398561Pancreatic lipaseinhibitorstructure-activity relationshipsanthraquinones |
| spellingShingle | 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 Discovery of natural anthraquinones as potent inhibitors against pancreatic lipase: structure-activity relationships and inhibitory mechanism Journal of Enzyme Inhibition and Medicinal Chemistry Pancreatic lipase inhibitor structure-activity relationships anthraquinones |
| title | Discovery of natural anthraquinones as potent inhibitors against pancreatic lipase: structure-activity relationships and inhibitory mechanism |
| title_full | Discovery of natural anthraquinones as potent inhibitors against pancreatic lipase: structure-activity relationships and inhibitory mechanism |
| title_fullStr | Discovery of natural anthraquinones as potent inhibitors against pancreatic lipase: structure-activity relationships and inhibitory mechanism |
| title_full_unstemmed | Discovery of natural anthraquinones as potent inhibitors against pancreatic lipase: structure-activity relationships and inhibitory mechanism |
| title_short | Discovery of natural anthraquinones as potent inhibitors against pancreatic lipase: structure-activity relationships and inhibitory mechanism |
| title_sort | discovery of natural anthraquinones as potent inhibitors against pancreatic lipase structure activity relationships and inhibitory mechanism |
| topic | Pancreatic lipase inhibitor structure-activity relationships anthraquinones |
| url | https://www.tandfonline.com/doi/10.1080/14756366.2024.2398561 |
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