Xanthones with multiple roles against diabetes : their synthesis, structure-activity relationship, and mechanism studies
© 2024 Wiley Periodicals LLC..
A four-step synthetic process has been developed to prepare 1,3,5,8-tetrahydroxyxanthone (2a) and its isomer 1,3,7,8-tetrahydroxyxanthone (2b). 25 more xanthones were also synthesized by a modified scheme. Xanthone 2a was identified as the most active inhibitor against both α-glucosidase and aldose reductase (ALR2), with IC50 values of 7.8 ± 0.5 μM and 63.2 ± 0.6 nM, respectively, which was far active than acarbose (35.0 ± 0.1 μM), and a little more active than epalrestat (67.0 ± 3.0 nM). 2a was also confirmed as the most active antioxidant in vitro with EC50 value of 8.9 ± 0.1 μM. Any structural modification including methylation, deletion, and position change of hydroxyl group in 2a will cause an activity loss in inhibitory and antioxidation. By applying a H2 O2 -induced oxidative stress nematode model, it was confirmed that xanthone 2a can be absorbed by Caenorhabditis elegans and is bioavailable to attenuate in vivo oxidative stress, including the effects on lifespan, superoxide dismutase, Catalase, and malondialdehyde. 2a was verified with in vivo hypoglycemic effect and mitigation of embryo malformations in high glucose. All our data support that xanthone 2a behaves triple roles and is a potential agent to treat diabetic mellitus, gestational diabetes mellitus, and diabetic complications.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:85 |
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| Enthalten in: |
Drug development research - 85(2024), 2 vom: 13. März, Seite e22170 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Ke, Youhong [VerfasserIn] |
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| Links: |
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| Themen: |
α-glucosidase |
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| Anmerkungen: |
Date Completed 15.03.2024 Date Revised 15.03.2024 published: Print Citation Status MEDLINE |
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| doi: |
10.1002/ddr.22170 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM369707095 |
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| 520 | |a A four-step synthetic process has been developed to prepare 1,3,5,8-tetrahydroxyxanthone (2a) and its isomer 1,3,7,8-tetrahydroxyxanthone (2b). 25 more xanthones were also synthesized by a modified scheme. Xanthone 2a was identified as the most active inhibitor against both α-glucosidase and aldose reductase (ALR2), with IC50 values of 7.8 ± 0.5 μM and 63.2 ± 0.6 nM, respectively, which was far active than acarbose (35.0 ± 0.1 μM), and a little more active than epalrestat (67.0 ± 3.0 nM). 2a was also confirmed as the most active antioxidant in vitro with EC50 value of 8.9 ± 0.1 μM. Any structural modification including methylation, deletion, and position change of hydroxyl group in 2a will cause an activity loss in inhibitory and antioxidation. By applying a H2 O2 -induced oxidative stress nematode model, it was confirmed that xanthone 2a can be absorbed by Caenorhabditis elegans and is bioavailable to attenuate in vivo oxidative stress, including the effects on lifespan, superoxide dismutase, Catalase, and malondialdehyde. 2a was verified with in vivo hypoglycemic effect and mitigation of embryo malformations in high glucose. All our data support that xanthone 2a behaves triple roles and is a potential agent to treat diabetic mellitus, gestational diabetes mellitus, and diabetic complications | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Xu, Qinfang |e verfasserin |4 aut | |
| 700 | 1 | |a Hu, Jianling |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Jianrun |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Shijian |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Zhijun |e verfasserin |4 aut | |
| 700 | 1 | |a Peng, Shuling |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Chao |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Zhenqiang |e verfasserin |4 aut | |
| 700 | 1 | |a Chen, Heru |e verfasserin |4 aut | |
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