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Cistobislactones A-B, two sixteen-membered spiro-linked macrocylic bislactones from marine octopus Cistopus indicus: new anti-inflammatory agents attenuate arachidonate 5-lipoxygenase
Medicinal Chemistry Research ( IF 2.6 ) Pub Date : 2021-09-08 , DOI: 10.1007/s00044-021-02790-x
Silpa Kunnappilly Paulose 1 , Kajal Chakraborty 2
Affiliation  

Biochemical analysis of secondary metabolites of marine old-woman octopus Cistopus indicus (family Octopodidae) led to the identification of two sixteen-membered spiro-linked macrocyclic bislactones, named as cistobislactone A and cistobislactone B with unprecedented feature of henicos framework, based on extensive spectroscopic analyses. Cistobislactone B exhibited potential inhibition property against arachidonate 5-lipoxygenase (IC50 2.18 mM) than that demonstrated by cistobislactone A (IC50 2.54 mM) and standard non-steroidal anti-inflammatory agent ibuprofen (IC50 4.50 mM) thus signifying the higher anti-inflammatory activity of the cistobislactone B analogue. The studied macrocyclic bislactones exhibited promising antioxidant potential, in which cistobislactone B exhibited potential radical quenching (IC50 2.33 mM) and hydrogen peroxide scavenging (IC50 1.81 mM) activities that were proximal to the commercial anti-oxidant α-tocopherol (IC50 ~ 1.60 mM). This further reinforced its attenuation property against arachidonate 5-lipoxygenase. Considerably greater electronic properties coupled with balanced hydrophobicity of cistobislactone B could ascribe the superior ligand-receptor interfaces leading to its anti-inflammatory activity. Molecular docking analysis of cistobislactone B with 5-lipoxygenase recorded lesser docking score (−12.24 kcal mol−1) and binding energy (−11.24 kcal mol−1), which further supported its anti-inflammatory activity. Cistobislactone B, with six fold lesser value of inhibition constant (Ki 5.76 nM) towards 5-lipoxygenase than that displayed by cistobislactone A, could describe the superior protein-ligand interactions of the former. The undescribed cistobislactone B might be a potential natural anti-inflammatory lead to moderate the odds of inflammatory pathologies.



中文翻译:

Cistobislactones AB,来自海洋章鱼 Cistopus indicus 的两个十六元螺环连接的大环双内酯:新的抗炎剂减弱花生四烯酸 5-脂氧合酶

对海洋老妇章鱼Cistopus indicus(Octopodidae 科)次级代谢产物的生化分析,基于广泛的光谱分析,鉴定出两个十六元螺环连接的大环双内酯,命名为具有前所未有的 Henicos 骨架特征的cistobislactone A 和cistobislactone B分析。Cistobislactone乙表现出对花生四烯酸5-脂氧合酶抑制的潜在性(IC 50 2.18毫米)比由cistobislactone甲证明(IC 50 2.54毫摩尔)和布洛芬标准的非甾体抗炎剂(IC 504.50 mM),因此表明顺式双内酯 B 类似物具有更高的抗炎活性。研究的大环双内酯表现出有希望的抗氧化潜力,其中顺式双内酯 B 表现出潜在的自由基猝灭 (IC 50 2.33 mM) 和过氧化氢清除 (IC 50 1.81 mM) 活性,与商业抗氧化剂α-生育酚 (IC 50~ 1.60 毫米)。这进一步增强了其对花生四烯酸 5-脂肪氧化酶的衰减特性。相当大的电子特性加上顺式双内酯 B 的平衡疏水性可以归因于优越的配体 - 受体界面,导致其抗炎活性。具有5-脂氧合酶的顺式双内酯B的分子对接分析记录了较低的对接评分(-12.24 kcal mol -1)和结合能(-11.24 kcal mol -1),这进一步支持了其抗炎活性。Cistobislactone B,抑制常数值小六倍 (K i5.76 nM) 对 5-脂氧合酶的影响比由cistobislactone A 显示的高,可以描述前者的优越的蛋白质-配体相互作用。未描述的顺式双内酯 B 可能是一种潜在的天然抗炎药,可减轻炎症病理的发生几率。

更新日期:2021-09-09
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