Background: Microglia are associated with neuroinflammation, which play a key role in the pathogenesis of neurodegenerative diseases. It has been reported that some quinazolines and quinazolinones possess anti-inflammatory properties. However, the pharmacological properties of certain quinazoline derivatives are still unknown.

Objective: The antioxidant, cytotoxic, and protective effects of a series of synthesized 2- trifluoromethylquinazolines (2, 4, and 5) and quinazolinones (6-8) in lipopolysaccharide (LPS)- murine microglia (BV2) and hydrogen peroxide (H₂O₂)-mouse neuroblastoma-2a (N2a) cells were investigated.

Method: The antioxidant activity of synthesized compounds was evaluated with ABTS and DPPH assays. The cytotoxic activities were determined by MTS assay in BV2 and N2a cells. The production of nitric oxide (NO) in LPS-induced BV2 microglia cells was quantified.

Results: The highest ABTS and DPPH scavenging activities were observed for compound 8 with 87.7% of ABTS scavenge percentage and 54.2% DPPH inhibition. All compounds were noncytotoxic in BV2 and N2a cells at 5 and 50 μg/mL. The compounds which showed the highest protective effects in LPS-induced BV2 and H₂O₂-induced N2a cells were 5 and 7. All tested compounds, except 4, also reduced NO production at concentrations of 50 μg/mL. The quinazolinone series 6-8 exhibited the highest percentage of NO reduction, ranging from 38 to 60%. Compounds 5 and 8 possess balanced antioxidant and protective properties against LPS- and H₂O₂-induced cell death, thus showing great potential to be developed into anti-inflammatory and neuroprotective agents.

Conclusion: Compounds 5 and 7 were able to protect the BV2 and N2a cells against LPS and H₂O₂ toxicity, respectively, at a low concentration (5 μg/mL). Compounds 6-8 showed potent reduction of NO production in BV2 cells.

背景：小胶质细胞与神经炎症有关，神经炎症在神经退行性疾病的发病机制中起关键作用。据报道，一些喹唑啉和喹唑啉酮具有抗炎特性。然而，某些喹唑啉衍生物的药理特性仍然未知。

目的：一系列合成的 2-三氟甲基喹唑啉（2、4 和 5）和喹唑啉酮（6-8）在脂多糖 (LPS)-鼠小胶质细胞 (BV2) 和过氧化氢 (H ₂ ) 中的抗氧化、细胞毒性和保护作用研究了 O ₂ )-小鼠神经母细胞瘤-2a (N2a) 细胞。

方法：通过 ABTS 和 DPPH 测定评估合成化合物的抗氧化活性。BV2和N2a细胞中的细胞毒活性通过MTS测定确定。量化 LPS 诱导的 BV2 小胶质细胞中一氧化氮 (NO) 的产生。

结果： 化合物 8 的 ABTS 和 DPPH 清除活性最高，ABTS 清除百分比为 87.7%，DPPH 抑制率为 54.2%。所有化合物在 5 和 50 μg/mL 时在 BV2 和 N2a 细胞中均无细胞毒性。在 LPS 诱导的 BV2 和 H ₂ O ₂诱导的 N2a 细胞中显示出最高保护作用的化合物是 5 和 7。所有测试的化合物，除了 4，还在 50 μg/mL 的浓度下减少了 NO 的产生。喹唑啉酮系列 6-8 表现出最高的 NO 还原百分比，范围从 38% 到 60%。化合物 5 和 8 对 LPS- 和 H ₂ O ₂具有平衡的抗氧化和保护性能诱导细胞死亡，因此显示出开发成抗炎和神经保护剂的巨大潜力。

结论：化合物5和7能够在低浓度(5 μg/mL)下分别保护BV2和N2a细胞免受LPS和H ₂ O ₂毒性。化合物 6-8 显示出 BV2 细胞中 NO 产生的有效减少。