Investigation of 2,3-diaryl-1,3-thiazolidin-4-ones as promising agents for reducing lipid accumulation in liver cells through AMPK activation: synthesis, in vitro, in silico and lipidomic studies
Issued Date
2026-01-01
Resource Type
eISSN
26328682
Scopus ID
2-s2.0-105040119287
Journal Title
Rsc Medicinal Chemistry
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SCOPUS
Bibliographic Citation
Rsc Medicinal Chemistry (2026)
Suggested Citation
Maiuthed A., Sandech N., Yang M.C., Krobthong S., Rukthong P., Sripha K., Imaram W., Aonsri C. Investigation of 2,3-diaryl-1,3-thiazolidin-4-ones as promising agents for reducing lipid accumulation in liver cells through AMPK activation: synthesis, in vitro, in silico and lipidomic studies. Rsc Medicinal Chemistry (2026). doi:10.1039/d6md00226a Retrieved from: https://repository.li.mahidol.ac.th/handle/123456789/117081
Title
Investigation of 2,3-diaryl-1,3-thiazolidin-4-ones as promising agents for reducing lipid accumulation in liver cells through AMPK activation: synthesis, in vitro, in silico and lipidomic studies
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Abstract
1,3-Thiazolidin-4-ones are versatile heterocyclic scaffolds with diverse biological activities, however efficient synthesis and identification of potent lipid-lowering derivatives remain challenging. Here, we report a rapid, scalable sealed-tube, acid-catalyzed three-component synthesis of 2,3-diaryl-1,3-thiazolidin-4-ones, enabling broad substrate tolerance and the preparation of thirty synthetic derivatives, including twelve novel compounds, with moderate to excellent yields (from 25% to quantitative yield). Biological evaluation in HepG2 cells identified compound 9y as a non-toxic lead with superior lipid-lowering activity in both prophylactic and therapeutic oleic acid-induced steatosis models, comparable to the clinically used hepatoprotective agent silymarin. Mechanistic studies revealed that 9y robustly activates AMPKα, promoting lipid catabolism while suppressing lipogenesis, as confirmed by western blot, immunofluorescence, and molecular docking. Lipidomic profiling further demonstrated that 9y selectively reduces pathogenic ceramide and phosphatidylethanolamine species, highlighting its broad lipidome remodeling potential. These results establish 9y as a promising lead for the treatment of fatty liver disease and provide a practical synthetic platform for the development of thiazolidin-4-one-based metabolic therapeutics.