A New Series of Ferulic Acid Amides Reveals an Unexpected Peroxiredoxin 1 Inhibition Activity With In Vivo Antidiabetic and Hypolipidemic Effects.

A New Series of Ferulic Acid Amides Reveals an Unexpected Peroxiredoxin 1 Inhibition Activity With In Vivo Antidiabetic and Hypolipidemic Effects. ChemMedChem. 2020 Oct 08;: Authors: Yasmin S, Cerchia C, Badavath VN, Laghezza A, Dal Piaz F, Mondal SK, Atlı Ö, Baysal M, Vadivelan S, S S, Siddique MUM, Pattnaik AK, Singh RP, Loiodice F, Jayaprakash V, Lavecchia A Abstract Insulin resistance is a major pathophysiological feature in the development of type 2 diabetes (T2DM). Ferulic acid is known for attenuating the insulin resistance and reducing the blood glucose in T2DM rats. In this work, we designed and synthesized a library of new ferulic acid amides (FAA), which could be considered as ring opening derivatives of the antidiabetic PPARγ agonists Thiazolidinediones (TZDs). However, since these compounds displayed weak PPAR transactivation capacity, we employed a proteomics approach to unravel their molecular target(s) and identified the peroxiredoxin 1 (PRDX1) as a direct binding target of FAAs. Interestingly, PRDX1, a protein with antioxidant and chaperone activity, has been implied in the development of T2DM by inducing hepatic insulin resistance. SPR, mass spectrometry-based studies, docking experiments and in vitro inhibition assay confirmed that compounds VIe and VIf bound PRDX1 and induced a dose-dependent inhibition. Furthermore, VIe and VIf significantly improved hyperglycemia and hyperlipidemia in streptozotocin-nicotinam...
Source: ChemMedChem - Category: Chemistry Authors: Tags: ChemMedChem Source Type: research