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Anti-inflammatory polyoxygenated furanocembranoids, salmacembranes A–B from the sea urchin Salmacis bicolor attenuate pro-inflammatory cyclooxygenases and lipoxygenase
Medicinal Chemistry Research ( IF 2.6 ) Pub Date : 2020-09-10 , DOI: 10.1007/s00044-020-02620-6
Prima Francis , Kajal Chakraborty

Two undescribed polyoxygenated furanocembranoid derivatives, methyl 15-(9-hydroxy-8-methoxy-2,12-dimethyl-15-oxa-bicyclo[10.2.1]pentadeca-2,4,6,11-tetraen-3-yl)propanoate (salmacembrane A) and 1-(16-methyl-2,16-dihydrofuran)-8-methoxy-12-methyl-20-oxabicyclo[10.2.1]pentadeca-2,4,6,11-tetraen-9-ol (salmacembrane B), were isolated from the organic extract of sea urchin Salmacis bicolor (family Temnopleuridae) by extensive chromatographic purification. Their structures were elucidated using detailed spectroscopic evidence. Salmacembrane A displayed significantly greater attenuation property against pro-inflammatory cyclooxygenase-2 (IC50 1.71 mM) than that exhibited by salmacembrane B (IC50 1.99 mM). Salmacembrane A could potentially inhibit 5-lipoxygenase (IC50 1.87 mM) and its activity was significantly greater than that exhibited by anti-inflammatory agent ibuprofen (IC50 4.50 mM, p < 0.05). The greater selectivity index (anti-cyclooxygense-2/anti-cyclooxygense-1) of salmacembrane A (1.06) than ibuprofen (0.43) further supported higher selectivity toward pro-inflammatory isoenzyme cyclooxygenase-2. Salmacembrane A displayed higher antioxidant properties against 2,2′-azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) and 2,2-diphenyl-1-picrylhydrazyl (IC50 1.57 and 1.65 mM, respectively) than those exhibited by salmacembrane B (IC50 > 1.85 mM). In addition, these antioxidant activities were comparable to the standard α-tocopherol (IC50 DPPH 1.51 mM, IC50 ABTS+ 1.70 mM p < 0.05). The higher electronic parameters obtained from structure–activity relationship analysis along with greater binding affinities of salmacembrane A at the active site of cyclooxygenase-2 ascribed its potential anti-inflammatory activity.



中文翻译:

海胆中的抗炎多氧呋喃类呋喃类化合物,海藻类A–B Salmacis bicolor可减弱促炎性环氧合酶和脂氧合酶

两种未描述的多氧呋喃呋喃类衍生物,甲基15-(9-羟基-8-甲氧基-2,12-二甲基-15-氧杂双环[10.2.1] pentadeca-2,4,6,11-四烯-3-基)丙酸酯(盐藻膜A)和1-(16-甲基-2,16-二氢呋喃)-8-甲氧基-12-甲基-20-氧杂双环[10.2.1] pentadeca-2,4,6,11-tetraen-9-通过广泛的色谱纯化从海胆Salmacis bicolor(Temnopleuridae家族)的有机提取物中分离出醇(Salmacembrane B)。使用详细的光谱学证据阐明了它们的结构。相较于Salmacembrane B(IC 50 1.99 mM),Salmacembrane A对促炎性环氧合酶2(IC 50 1.71 mM)表现出更大的衰减特性。Salmacembrane A可能会抑制5-脂氧合酶(IC50. 1.87 mM),其活性显着高于抗炎药布洛芬(IC 50 4.50 mM,p  <0.05)。相比于布洛芬(0.43),柳树膜A(1.06)的选择性指数(anti-cyclooxygense-2 / anti-cyclooxygense-1)更高,进一步支持了对促炎同工酶环氧合酶2的更高选择性。相比于金银膜,Salmacembrane A对2,2'-叠氮基双(3-乙基苯并噻唑啉-6-磺酸)和2,2-二苯基-1-吡啶并肼基(IC 50分别为1.57和1.65 mM)表现出更高的抗氧化性能。B(IC 50  > 1.85 mM)。此外,这些抗氧化活性与标准α-生育酚(IC 50DPPH 1.51 mM,IC 50 ABTS + 1.70 mM p  <0.05)。从结构-活性关系分析获得的更高的电子参数,以及在加氧合酶-2的活性位点上具有更大的结合度的salmacembrane A归因于其潜在的抗炎活性。

更新日期:2020-09-10
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