Synthesis of benzylated amine-substituted xanthone derivatives and their antioxidant and anti-inflammatory activities |
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Authors: | Ka Woong Wong Soek Sin Teh Kung Pui Law Intan Safinar Ismail Kohei Sato Nobuyuki Mase Siau Hui Mah |
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Affiliation: | 1. School of Biosciences, Faculty of Health & Medical Sciences, Taylor's University, Subang Jaya, Selangor, Malaysia;2. Engineering and Processing Division, Energy and Environment Unit, Malaysian Palm Oil Board, Kajang, Selangor, Malaysia;3. School of Pre-University Studies, Taylor's College, Subang Jaya, Selangor, Malaysia;4. Natural Medicine and Products Research Laboratory, Institute of Bioscience, Universiti Putra Malaysia, Serdang, Selangor, Malaysia;5. Department of Applied Chemistry and Biochemical Engineering, Faculty of Engineering, Shizuoka University, Shizuoka, Japan Research Institute of Green Science and Technology, Shizuoka University, Shizuoka, Japan |
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Abstract: | 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 H2O2 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. |
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Keywords: | halogenated benzylamine hydrogen peroxide scavenging activity nitric oxide O-alkylation pro-inflammatory cytokines |
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