Synthesis of Rottlerone Analogues and Evaluation of Their α-Glucosidase and DPP-4 Dual Inhibitory and Glucose Consumption-Promoting Activity
Our previous study found that desmethylxanthohumol (<b>1</b>) inhibited α-glucosidase in vitro. Recently, further investigations revealed that dehydrocyclodesmethylxanthohumol (<b>2</b>) and its dimer analogue rottlerone (<b>3</b>) exhibited more potent α-glucosid...
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MDPI AG
2021-02-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/4/1024 |
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| author | Yinan Zhang Haibo Wang Yan Wu Xue Zhao Zhihong Yan Robert H. Dodd Peng Yu Kui Lu Hua Sun |
| author_facet | Yinan Zhang Haibo Wang Yan Wu Xue Zhao Zhihong Yan Robert H. Dodd Peng Yu Kui Lu Hua Sun |
| author_sort | Yinan Zhang |
| collection | DOAJ |
| description | Our previous study found that desmethylxanthohumol (<b>1</b>) inhibited α-glucosidase in vitro. Recently, further investigations revealed that dehydrocyclodesmethylxanthohumol (<b>2</b>) and its dimer analogue rottlerone (<b>3</b>) exhibited more potent α-glucosidase inhibitory activity than <b>1</b>. The aim of this study was to synthesize a series of rottlerone analogues and evaluate their α-glucosidase and DPP-4 dual inhibitory activity. The results showed that compounds <b>4d</b> and <b>5d</b> irreversibly and potently inhibited α-glucosidase (IC<sub>50</sub> = 0.22 and 0.12 μM) and moderately inhibited DPP-4 (IC<sub>50</sub> = 23.59 and 26.19 μM), respectively. In addition, compounds <b>4d</b> and <b>5d</b> significantly promoted glucose consumption, with the activity of <b>5d</b> at 0.2 μM being comparable to that of metformin at a concentration of 1 mM. |
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| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T00:51:50Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-b9a1cfaef5cc43ab84327baa0a8df9312023-12-11T17:11:47ZengMDPI AGMolecules1420-30492021-02-01264102410.3390/molecules26041024Synthesis of Rottlerone Analogues and Evaluation of Their α-Glucosidase and DPP-4 Dual Inhibitory and Glucose Consumption-Promoting ActivityYinan Zhang0Haibo Wang1Yan Wu2Xue Zhao3Zhihong Yan4Robert H. Dodd5Peng Yu6Kui Lu7Hua Sun8China International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, ChinaChina International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, ChinaChina International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, ChinaChina International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, ChinaChina International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, ChinaChina International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, ChinaChina International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, ChinaChina International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, ChinaChina International Science and Technology Cooperation Base of Food Nutrition/Safety and Medicinal Chemistry, College of Biotechnology, Tianjin University of Science & Technology, Tianjin 300457, ChinaOur previous study found that desmethylxanthohumol (<b>1</b>) inhibited α-glucosidase in vitro. Recently, further investigations revealed that dehydrocyclodesmethylxanthohumol (<b>2</b>) and its dimer analogue rottlerone (<b>3</b>) exhibited more potent α-glucosidase inhibitory activity than <b>1</b>. The aim of this study was to synthesize a series of rottlerone analogues and evaluate their α-glucosidase and DPP-4 dual inhibitory activity. The results showed that compounds <b>4d</b> and <b>5d</b> irreversibly and potently inhibited α-glucosidase (IC<sub>50</sub> = 0.22 and 0.12 μM) and moderately inhibited DPP-4 (IC<sub>50</sub> = 23.59 and 26.19 μM), respectively. In addition, compounds <b>4d</b> and <b>5d</b> significantly promoted glucose consumption, with the activity of <b>5d</b> at 0.2 μM being comparable to that of metformin at a concentration of 1 mM.https://www.mdpi.com/1420-3049/26/4/1024rottleroneα-glucosidase inhibitorDPP-4 inhibitorinhibitory mechanismglucose consumption |
| spellingShingle | Yinan Zhang Haibo Wang Yan Wu Xue Zhao Zhihong Yan Robert H. Dodd Peng Yu Kui Lu Hua Sun Synthesis of Rottlerone Analogues and Evaluation of Their α-Glucosidase and DPP-4 Dual Inhibitory and Glucose Consumption-Promoting Activity Molecules rottlerone α-glucosidase inhibitor DPP-4 inhibitor inhibitory mechanism glucose consumption |
| title | Synthesis of Rottlerone Analogues and Evaluation of Their α-Glucosidase and DPP-4 Dual Inhibitory and Glucose Consumption-Promoting Activity |
| title_full | Synthesis of Rottlerone Analogues and Evaluation of Their α-Glucosidase and DPP-4 Dual Inhibitory and Glucose Consumption-Promoting Activity |
| title_fullStr | Synthesis of Rottlerone Analogues and Evaluation of Their α-Glucosidase and DPP-4 Dual Inhibitory and Glucose Consumption-Promoting Activity |
| title_full_unstemmed | Synthesis of Rottlerone Analogues and Evaluation of Their α-Glucosidase and DPP-4 Dual Inhibitory and Glucose Consumption-Promoting Activity |
| title_short | Synthesis of Rottlerone Analogues and Evaluation of Their α-Glucosidase and DPP-4 Dual Inhibitory and Glucose Consumption-Promoting Activity |
| title_sort | synthesis of rottlerone analogues and evaluation of their α glucosidase and dpp 4 dual inhibitory and glucose consumption promoting activity |
| topic | rottlerone α-glucosidase inhibitor DPP-4 inhibitor inhibitory mechanism glucose consumption |
| url | https://www.mdpi.com/1420-3049/26/4/1024 |
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