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Synthesized 2-Trifluoromethylquinazolines and Quinazolinones Protect BV2 and N2a Cells against LPS- and H 2 O 2 -induced Cytotoxicity.
- Source :
-
Medicinal chemistry (Shariqah (United Arab Emirates)) [Med Chem] 2021; Vol. 17 (6), pp. 623-629. - Publication Year :
- 2021
-
Abstract
- 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.<br />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 (H <subscript>2</subscript> O <subscript>2</subscript> )-mouse neuroblastoma-2a (N2a) cells were investigated.<br />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.<br />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 H <subscript>2</subscript> O <subscript>2</subscript> -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 H <subscript>2</subscript> O <subscript>2</subscript> -induced cell death, thus showing great potential to be developed into anti-inflammatory and neuroprotective agents.<br />Conclusion: Compounds 5 and 7 were able to protect the BV2 and N2a cells against LPS and H <subscript>2</subscript> O <subscript>2</subscript> toxicity, respectively, at a low concentration (5 μg/mL). Compounds 6-8 showed potent reduction of NO production in BV2 cells.<br /> (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)
- Subjects :
- Animals
Cell Line, Tumor
Chemistry Techniques, Synthetic
Dose-Response Relationship, Drug
Hydrogen Peroxide antagonists & inhibitors
Lipopolysaccharides antagonists & inhibitors
Mice
Neuroprotective Agents chemistry
Nitric Oxide biosynthesis
Quinazolines chemistry
Cytoprotection drug effects
Hydrogen Peroxide toxicity
Lipopolysaccharides toxicity
Neuroprotective Agents chemical synthesis
Neuroprotective Agents pharmacology
Quinazolines chemical synthesis
Quinazolines pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1875-6638
- Volume :
- 17
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Medicinal chemistry (Shariqah (United Arab Emirates))
- Publication Type :
- Academic Journal
- Accession number :
- 31849289
- Full Text :
- https://doi.org/10.2174/1573406416666191218095635