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
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
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.