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ORIGINAL RESEARCH article

Front. Pharmacol.
Sec. Neuropharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1509520
This article is part of the Research Topic Exploring the Key Targets and Compounds That Manipulate Brain Neurocircuits Against Mental Disorders and Psychiatric Volume II View all 13 articles

Synthesis of 2H-1,4-Benzoxazin-3(4H)-one Derivatives Modified with 1,2,3-Triazole and Their Anti-inflammatory Activity in LPS-induced BV-2 Cells

Provisionally accepted
Xixi Hou Xixi Hou 1Longfei Mao Longfei Mao 2*Huibin Zhang Huibin Zhang 2Lan Wang Lan Wang 2Baoyu He Baoyu He 3Jingjing Guo Jingjing Guo 3Jianji Wang Jianji Wang 1
  • 1 Henan Normal University, Xinxiang, Henan Province, China
  • 2 Henan University of Science and Technology, Luoyang, China
  • 3 Macao Polytechnic University, Macau, Macao, SAR China

The final, formatted version of the article will be published soon.

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

    Keywords: 1, 2, 3-triazoles, 2H-1, 4-benzoxazin-3(4H)-one, Microglial cells, LPS-induced, antiinflammatory

    Received: 11 Oct 2024; Accepted: 18 Dec 2024.

    Copyright: © 2024 Hou, Mao, Zhang, Wang, He, Guo and Wang. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Longfei Mao, Henan University of Science and Technology, Luoyang, China

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.