Synthesis of benzylated amine-substituted xanthone derivatives and their antioxidant and anti-inflammatory activities.
Ka Woong WongSoek Sin TehKung Pui LawIntan Safinar IsmailKohei SatoNobuyuki MaseSiau Hui MahPublished in: Archiv der Pharmazie (2022)
Oxidative stress and its constant companion, inflammation, play a critical part in the pathogenesis of many acute and chronic illnesses. The discovery of new multi-targeted drug candidates with antioxidant and anti-inflammatory properties is deemed necessary. Thus, a series of novel xanthone derivatives with halogenated benzyl (4b-4d, 4f-4h) and methoxylated benzyl groups (4e) attached to the butoxy amine substituent were synthesized in this study. The synthesized xanthone derivatives exhibited stronger antioxidant activity against H 2 O 2 scavenging than the standard drug, α-tocopherol, but weaker towards DPPH scavenging and ferrous ion chelation. Besides that, 4b-4d, 4f-4h demonstrated good anti-inflammatory activities through NO production inhibition towards lipopolysaccharide (LPS)-induced RAW 264.7 cells and showed 2-4 times stronger effects than the standard drug, diclofenac sodium. Moreover, compound 4b with two brominated benzyl groups attached to the butoxy amine substituent suppressed the production of pro-inflammatory cytokines, TNF-α and IL-1β, significantly. Structure-activity relationship elucidated that the halogenated benzylamine substituent plays an important role in contributing the antioxidant and anti-inflammatory activities of xanthones. In summary, xanthone 4b was identified as a potential lead compound to be further developed into antioxidant and anti-inflammatory drugs. Thus, further studies on the related mechanisms of action of 4b are recommended.
Keyphrases
- anti inflammatory
- structure activity relationship
- lps induced
- oxidative stress
- inflammatory response
- drug induced
- induced apoptosis
- anti inflammatory drugs
- small molecule
- liver failure
- emergency department
- dna damage
- respiratory failure
- high throughput
- molecular docking
- signaling pathway
- cell death
- drug delivery
- molecular dynamics simulations
- extracorporeal membrane oxygenation
- aortic dissection
- acute respiratory distress syndrome