AMPK Activation by 2′-Hydroxy-2,4,5-Trimethoxychalcone Derivatives in Podocyte Cells
4
Issued Date
2025-01-01
Resource Type
ISSN
18607179
eISSN
18607187
Scopus ID
2-s2.0-105007848548
Pubmed ID
40411518
Journal Title
Chemmedchem
Rights Holder(s)
SCOPUS
Bibliographic Citation
Chemmedchem (2025)
Suggested Citation
Nguyen V.D., Muanprasat C., Kaewin S., Poolsri W., Chavasiri W. AMPK Activation by 2′-Hydroxy-2,4,5-Trimethoxychalcone Derivatives in Podocyte Cells. Chemmedchem (2025). doi:10.1002/cmdc.202500177 Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/110774
Title
AMPK Activation by 2′-Hydroxy-2,4,5-Trimethoxychalcone Derivatives in Podocyte Cells
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Abstract
Activating AMP-activated protein kinase (AMPK) using chalcones has emerged as a potential therapeutic strategy for managing diabetes mellitus (DM) and diabetic nephropathy. This research focuses on discovering new chalcone derivatives with a stronger ability to stimulate AMPK in podocytes compared to 2′-hydroxychalcones 1, 2, and 3 reported from the earlier research. The results show that hydrogenated products (4–6) cannot exhibit considerably improved activity. Additionally, 2′-hydroxychalcone bearing 2,4,5-triethoxy groups on the B-ring (10) and 2,4,5-trimethoxychalcones bearing 2′,4′-, 2′,5′-, or 2′,6′-dimethoxy groups on the A-ring (17–19) demonstrate potent AMPK activation with fold changes of 2.69, 2.36, 3.22, and 2.17, respectively, surpassing both the reference compound 1 (1.28) and metformin (1.88). The structure–activity relationship shows that inserting dimethoxy groups on the A-ring can strengthen the activity better than without inserting any group or inserting other moieties such as hydroxy, methylenedioxy, amino, trifluoromethyl, bromo, acetyl, 2,3-dihydro-1,4-dioxin ring, and benzene ring. Notably, 2,4,5-trimethoxychalcone 23 possessing 2′,4′,5′-trimethoxy groups, bis-chalcones 35 and 36, and tris-chalcone 37 is poorly soluble in the experiments. Compound 18 exhibits more potent activity than compounds 2 and 3 (2.48 and 2.73, respectively); therefore, it would be a promising candidate for further studies on AMPK-stimulating activity.