Design, synthesis, and anti-inflammatory activity of 2H-1,4-benzoxazin-3(4H)-one derivatives modified with 1,2,3-triazole in LPS-induced BV-2 cells

Frontiers in Pharmacology, Journal Year: 2025, Volume and Issue: 15

Published: Jan. 20, 2025

Given the potent anti-inflammatory properties of 1,2,3-triazole structure and wide use 2H-1,4-benzoxazin-3(4H)-one in developing treatments for neurodegenerative diseases, a series derivatives were synthesized by introducing moiety. Screening activity microglial cells revealed that compounds e2, e16, e20 exhibited most promising effects without significant cytotoxicity. These effectively reduced LPS-induced NO production significantly decreased transcription levels pro-inflammatory cytokines IL-1β, IL-6, TNF-α. Furthermore, they downregulated protein inflammation-related enzymes iNOS COX-2 response to LPS stimulation. To further investigate mechanisms these microglia, intracellular ROS activation Nrf2-HO-1 signaling pathway analyzed. The results indicated activated pathway, production, alleviated inflammation. Molecular docking studies suggested could interact with Nrf2-related binding sites, preventing its degradation Keap1. Additionally, acute toxicity tests mice demonstrated compound e16 favorable safety.

Language: Английский

Design, synthesis, and antiproliferative activity evaluation of novel cyclic secondary amine containing dithiocarbamate derivatives as potent EGFR inhibitors

Journal of Molecular Structure, Journal Year: 2025, Volume and Issue: unknown, P. 142036 - 142036

Published: March 1, 2025

Language: Английский