Synthesis of novel pyrazole derivatives and neuroprotective effect investigation

Spinal cord injuries (SCIs) cause irreversible damage and lasting neurological impairments. Current treatments are limited to surgical and pharmaceutical interventions, underscoring the need for novel agents. In this study, 27 novel pyrazole derivatives were designed, synthesised. The anti-inflammatory and antioxidant activities of the compounds were systematically evaluated utilising lipopolysaccharide-stimulated BV2 microglial cells. Anti-inflammatory activity was assessed by quantifying the mRNA expression levels of key pro-inflammatory cytokines [tumour necrosis factor-α, interleukin-1β, and interleukin-6 (IL-6)] via quantitative reverse transcription polymerase chain reaction. Among the synthesised derivatives, compound 6g demonstrated the most potent anti-inflammatory effect, exhibiting an IC₅₀ value of 9.562 μM for the suppression of IL-6 expression and no significant cytotoxicity was observed. Notable, compound 6g exhibited better inhibitory potency against IL-6 expression compared to the anti-inflammatory drugs dexamethasone and Celecoxib. These findings strongly support the potential of compound 6g as a promising therapeutic candidate for mitigating secondary inflammation in SCI.