Marine Biotechnology Division, Central Marine Fisheries Research Institute, Ernakulam North, P.B. No. 1603, Cochin 682018, Kerala, India.
Marine Biotechnology Division, Central Marine Fisheries Research Institute, Ernakulam North, P.B. No. 1603, Cochin 682018, Kerala, India.
Bioorg Chem. 2021 Apr;109:104663. doi: 10.1016/j.bioorg.2021.104663. Epub 2021 Jan 21.
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 (IC 0.89 mM) than that displayed by procerolide A, whereas 5-lipoxygenase inhibitory activity of procerolide B (IC 1.08 mM) was significantly greater than that displayed by procerolide A (IC 0.95 mM) and anti-inflammatory agent ibuprofen (IC 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 cm) 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.
环氧化酶-2 被认为能够催化花生四烯酸生成炎症性前列腺素。对环氧化酶-2 的抑制潜力以及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，从海洋海绵 Clathria procera（Microcionidae 科）的有机提取物中分离得到两种未描述的十四元大环内酯，即 prololide A 和 B。Prololide B 对环氧化酶-2 的抑制潜力（IC 0.89 mM）大于 prololide A，而 prololide B 的 5-脂氧合酶抑制活性（IC 1.08 mM）明显大于 prololide A（IC 0.95 mM）和抗炎剂布洛芬（IC 4.50 mM）。此外，与合成剂（0.43）相比，prololides 的抗炎选择性指数（~1.3）更高，这归因于化合物对环氧化酶-2 的选择性抑制。与标准相比，化合物具有更高的电子性质（拓扑极性表面积> 100）和更小的空间性质（摩尔体积<300 cm），这支持了它们具有显著的抗炎潜力。此外，prololide B 与环氧化酶-2 的氨基酸残基的结合能相对较低（-9.82 kcal/mol），从而识别其在炎症发病机制中的潜在治疗用途。
