Synthesis of benzylated amine‐substituted xanthone derivatives and their antioxidant and anti‐inflammatory activities
Synthesis of benzylated amine‐substituted xanthone derivatives and their antioxidant and anti‐inflammatory activities
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苄基胺取代呫吨酮衍生物的合成及其抗氧化和抗炎活性
DOI：
10.1002/ardp.202200418
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发表时间：
2022
影响因子：
5.1
通讯作者：
Mah Siau Hui
中科院分区：
文献类型：
--
作者：
Wong Ka Woong;Teh Soek Sin;Law Kung Pui;Ismail Intan Safinar;Sato Kohei;Mase Nobuyuki;Mah Siau Hui
氧化应激及其持续的伴随物炎症在许多急性和慢性疾病的发病机制中起着关键作用。发现具有抗氧化和抗炎特性的新的多靶向候选药物被认为是必要的。因此，本研究合成了一系列新的氧杂蒽酮衍生物，其具有卤代苄基（4 b-4d，4f-4 h）和甲氧基化苄基（4 e）连接到丁氧基胺取代基上。合成的口山酮衍生物对H2 O2的清除能力强于标准药物α-生育酚，但对DPPH自由基的清除能力和亚铁离子螯合能力较弱。此外，4 b-4d、4f-4 h通过抑制脂多糖（LPS）诱导的RAW 264.7细胞的NO产生而显示出良好的抗炎活性，并且显示出比标准药物双氯芬酸钠强2-4倍的效果。此外，具有两个连接到丁氧基胺取代基的溴化苄基的化合物4 b显著抑制促炎细胞因子TNF-α和IL-1β的产生。构效关系表明，卤代苄胺取代基在氧杂蒽酮的抗氧化和抗炎活性中起着重要作用。总之，氧杂蒽酮4 b被确定为潜在的先导化合物，可进一步开发为抗氧化剂和抗炎药物。因此，建议进一步研究4的相关作用机制。
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 H2O2scavenging than the standard drug, α‐tocopherol, but weaker towards DPPH scavenging and ferrous ion chelation. Besides that,4b–4d,4f–4hdemonstrated 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, compound4bwith 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, xanthone4bwas 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 of4bare recommended.