TY  - JOUR
T1  - Design, Biological Evaluation, and PPARγ Modulation of Nitro- and Acetamidophenoxyisobutyric Acids as Antidiabetic Agents
A1  - Kenji Nakamura
A1  - Aiko Fujita
JF  - Pharmaceutical Sciences and Drug Design
JO  - Pharm Sci Drug Des
SN  - 3062-4428
Y1  - 2025
VL  - 5
IS  - 1
DO  - 10.51847/NlNkX8Fh31
SP  - 283
EP  - 296
N2  - Four isobutyric acid derivatives, including two nitro- and two acetamido-substituted analogues, were synthesized through a two-step procedure and fully characterized by spectroscopic techniques. Treatment of 3T3-L1 adipocytes with compounds 1–4 resulted in elevated mRNA expression levels of PPARγ and GLUT-4, two well-established molecular targets in diabetes therapy, whereas no detectable induction of PPARα expression was observed in vitro. Computational docking and molecular dynamics simulations supported favorable binding interactions between the synthesized molecules and PPARγ. In vivo evaluations demonstrated that all tested compounds exerted antihyperglycemic effects linked to enhanced insulin sensitivity. Among the series, nitrocompound 2 exhibited the most pronounced activity and oral bioavailability. Its mechanism of action may involve selective modulation of PPARγ, potentially facilitated by an additional stabilizing interaction with the Gln-286 residue. Overall, these findings identify nitrocompound 2 as a promising experimental candidate for antidiabetic drug development.
UR  - https://galaxypub.co/article/design-biological-evaluation-and-pparg-modulation-of-nitro-and-acetamidophenoxyisobutyric-acids-a-gql5gg0kru7fgig
ER  -