Department of Agronomy and Medicinal Plant Resources, Gyeongnam National University of Science and Technology, Jinju 52725, Korea.
Department of Oceanography, Kunsan National University, Gunsan 54150, Korea.
Mar Drugs. 2021 Feb 4;19(2):90. doi: 10.3390/md19020090.
Using bio-guided fractionation and based on the inhibitory activities of nitric oxide (NO) and prostaglandin E2 (PGE2), eight isoquinolinequinone derivatives (-) were isolated from the marine sponge sp. Among these, methyl -demethylrenierate () is a noble ester, whereas compounds and are new -demethyl derivatives of known isoquinolinequinones. Compound was assigned as a new 21-dehydroxyrenieramycin F. Anti-inflammatory activities of the isolated compounds were tested in a co-culture system of human epithelial Caco-2 and THP-1 macrophages. The isolated derivatives showed variable activities. -demethyl renierone () showed the highest activity, while and showed moderate activities. These bioactive isoquinolinequinones inhibited lipopolysaccharide and interferon gamma-induced production of NO and PGE2. Expression of inducible nitric oxide synthase, cyclooxygenase-2, and the phosphorylation of MAPKs were down-regulated in response to the inhibition of NF-κB nuclear translocation. In addition, nuclear translocation was markedly promoted with a subsequent increase in the expression of HO-1. Structure-activity relationship studies showed that the hydroxyl group in and , and the N-formyl group in may be key functional groups responsible for their anti-inflammatory activities. These findings suggest the potential use of sp. and its metabolites as pharmaceuticals treating inflammation-related diseases including inflammatory bowel disease.
利用生物导向分离，并基于一氧化氮 (NO) 和前列腺素 E2 (PGE2) 的抑制活性，从海洋海绵 sp. 中分离得到了 8 种异喹啉醌衍生物 (-)。其中，甲基 - 去甲雷尼尔酸盐 () 是一种高贵的酯，而化合物 和 是已知异喹啉醌的新 - 去甲衍生物。化合物 被指定为新的 21-去羟雷尼尔霉素 F。在人上皮 Caco-2 和 THP-1 巨噬细胞共培养系统中测试了分离化合物的抗炎活性。分离得到的衍生物表现出不同的活性。-去甲雷尼尔酮 () 表现出最高的活性，而 和 表现出中等活性。这些具有生物活性的异喹啉醌抑制脂多糖和干扰素 γ 诱导的 NO 和 PGE2 的产生。诱导型一氧化氮合酶、环氧化酶-2 的表达以及 MAPKs 的磷酸化水平下调，这与 NF-κB 核易位的抑制有关。此外，NF-κB 核易位明显促进，随后 HO-1 的表达增加。构效关系研究表明，在 和 中的羟基和 中的 N-甲酰基可能是负责其抗炎活性的关键功能基团。这些发现表明，海洋海绵 sp. 及其代谢物可能具有治疗炎症相关疾病（包括炎症性肠病）的药用潜力。
