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Procerolides A-B from Microcionidae marine sponge Clathria procera: Anti-inflammatory macrocylic lactones with selective cyclooxygenase-2 attenuation properties
Bioorganic Chemistry ( IF 4.5 ) Pub Date : 2021-01-21 , DOI: 10.1016/j.bioorg.2021.104663
Kajal Chakraborty 1 , Prima Francis 1
Affiliation  

Cyclooxygenase-2 has been recognized to catalyze the formation of inflammatory prostaglandins from arachidonic acid. Attenuation potential against cyclooxygenase-2 coupled with greater anti-inflammatory selectivity index were contemplated to be vital indicators to assess anti-inflammatory activities of bioactive compounds. In the present study, two undescribed fourteen-membered macrocyclic lactones, procerolide A and B were isolated to homogeneity from the organic extract of the marine sponge Clathria procera (family: Microcionidae). Procerolide B exhibited greater attenuation potential against cyclooxygenase-2 (IC50 0.89 mM) than that displayed by procerolide A, whereas 5-lipoxygenase inhibitory activity of procerolide B (IC50 1.08 mM) was significantly greater than that displayed by procerolide A (IC50 0.95 mM) and anti-inflammatory agent ibuprofen (IC50 4.50 mM). Additionally, greater anti-inflammatory selectivity index of the procerolides (~1.3) than the synthetic agent (0.43) was accounted for the selective inhibition of the compounds towards cyclooxygenase-2. Higher electronic properties (topological polar surface area of > 100) along with lesser steric properties (molar volume < 300 cm3) of the compounds compared to the standard supported their significant anti-inflammatory potential. Additionally, procerolide B exhibited comparatively lesser binding energy with aminoacyl residues of cyclooxygenase-2 (-9.82 kcal/mol) thereby recognizing its prospective therapeutic use against inflammatory pathogenesis.



中文翻译:

来自 Microcionidae 海洋海绵 Clathria procera 的 Procerolides AB:具有选择性环加氧酶 2 衰减特性的抗炎大环内酯

Cyclooxygenase-2 已被认为可催化花生四烯酸形成炎性前列腺素。对环加氧酶 2 的衰减潜力加上更大的抗炎选择性指数被认为是评估生物活性化合物抗炎活性的重要指标。在本研究中,两个未描述的十四元大环内酯,procerolide A 和 B 从海洋海绵Clathria procera(家族:Microcionidae)的有机提取物中分离到均质。Procerolide乙表现出更大的衰减电势对环氧合酶-2(IC 50 0.89毫米)比由procerolide甲显示,而5-脂氧合酶procerolide B的抑制活性(IC 501.08 mM) 显着大于 procerolide A (IC 50 0.95 mM) 和抗炎剂布洛芬 (IC 50 4.50 mM) 显示的值。此外,与合成试剂 (0.43) 相比,procerolides (~1.3) 的抗炎选择性指数更高,这被解释为化合物对环加氧酶-2 的选择性抑制。较高的电子特性(拓扑极性表面积 > 100)以及较小的空间特性(摩尔体积 < 300 cm 3) 的化合物与标准相比支持它们显着的抗炎潜力。此外,procerolide B 与 cyclooxygenase-2 (-9.82 kcal/mol) 的氨酰基残基的结合能相对较低,从而认识到其对炎症发病机制的前瞻性治疗用途。

更新日期:2021-02-11
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