Molecular hybridization of syringaldehyde and fibrate pharmacophores yields a novel derivative with potent, multi-target lipid-lowering activity

This study aimed to reduce the hepatotoxicity of traditional fibrate drugs. A molecular hybridization strategy was adopted to synthesize a series of syringaldehyde-based fibrate derivatives. Screening revealed that T2 exhibited the most pronounced reduction in TG and TC levels in a dose-dependent manner in the Triton WR 1339-induced hyperlipidemia model. Moreover, a high-fat dietary regimen (HFD)-induced hyperlipidemia model was utilized to assess the lipid-lowering potential of T2. The findings indicated that T2 exerted a significant lipid-lowering effect and reduced the ALT and AST levels, thereby ameliorating pathological alterations in the liver tissue. Additionally, the activity of SOD was significantly enhanced. It was observed that the content of the lipid peroxidation product MDA was reduced considerably, and the levels of IL-6 and TNF-α were decreased. These changes suggest that T2 is capable of exerting anti-inflammatory and antioxidant effects. Findings from research on the lipid-lowering mechanism indicate that T2 enhances PPAR-α protein expression in the liver and interacts strongly with its active site. These results suggest that T2 is a potential novel multifunctional lipid-lowering fibrate candidate compound.