Discovery of novel indazole derivatives with anti-neuroinflammatory activity.

Authors

Qingqing Zhang, Xixi Hou, Xuanwei Zhang, Yimian Wang, Yaquan Cao, Lan Wang, Longfei Mao

Published in

RSC medicinal chemistry. Jun 23, 2026. Epub Jun 23, 2026.

Abstract

This study focuses on the critical role of microglia-mediated neuroinflammation in various neurological disorders. Utilizing the indazole heterocycle-a scaffold known for its structural plasticity and multi-target potential-as the core structure, a series of derivatives were designed and synthesized with the aim of screening and elucidating their anti-inflammatory activity and underlying mechanisms. The activities of the compounds were systematically evaluated in an in vitro LPS-stimulated BV-2 microglial model using Griess assay, MTT assay, qPCR, and western blotting. Among the 15 derivatives obtained, compound 5o exhibited the most potent anti-inflammatory activity (IC₅₀ = 8.45 ± 0.64 μM). Its mechanism of action involves the regulation of microglial polarization-significantly suppressing M1 phenotype markers such as NO, IL-1β, IL-6, TNF-α, iNOS, and COX-2. Further mechanistic studies revealed that this effect is mediated through positive regulation nuclear translocation of Nrf2. In summary, this study demonstrates that the indazole derivative 5o exerts anti-neuroinflammatory effects by inhibiting microglial M1 polarization, providing a promising lead compound and a robust pharmacological basis for the development of novel therapeutic strategies targeting neuroinflammatory diseases.

PMID:
42491970
Bibliographic data and abstract were imported from PubMed on 24 Jul 2026.

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