Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China.
Institute of Microbial Pharmaceuticals, College of Life and Health Sciences, Northeastern University, Shenyang 110819, China.
Bioorg Chem. 2021 Jun;111:104898. doi: 10.1016/j.bioorg.2021.104898. Epub 2021 Apr 8.
Violacin A, a chromanone derivative, isolated from a fermentation broth of Streptomyces violaceoruber, has excellent anti-inflammatory potential. Herein, a biogenetically modeled approach to synthesize violacin A and twenty-five analogues was described, which involved the preparation of aromatic polyketide precursor through Claisen condensation and its spontaneous cyclization. The inhibitory effect on nitric oxide (NO) production of all synthetic molecules was evaluated by lipopolysaccharide (LPS)-induced Raw264.7 cells. The results revealed that introduction of aliphatic amine moieties on C-7 obviously improved the anti-inflammation effect of violacin A, and also the aromatic ether instead of ketone group at side chain was favorable to increase the activity. Among them, analogue 7a and 16d were screened as the most effective anti-inflammatory candidates. Molecular mechanism research revealed that 7a and 16d acquired anti-inflammatory ability due to the inhibition of NF-κB signaling pathway.
紫罗兰色 A 是一种色满酮衍生物，从紫色链霉菌发酵液中分离得到，具有优异的抗炎潜力。本文描述了一种生物模拟方法来合成紫罗兰色 A 和 25 种类似物，包括通过 Claisen 缩合制备芳香聚酮前体及其自发环化。通过脂多糖 (LPS) 诱导的 Raw264.7 细胞评估所有合成分子对一氧化氮 (NO) 产生的抑制作用。结果表明，在 C-7 位引入脂肪胺部分明显提高了紫罗兰色 A 的抗炎效果，并且侧链上的芳香醚取代酮基也有利于提高活性。其中，类似物 7a 和 16d 被筛选为最有效的抗炎候选物。分子机制研究表明，7a 和 16d 通过抑制 NF-κB 信号通路获得抗炎能力。
