Yu Pan, Xia Chao-Jie, Li Dong-Dong, Wang Zhenzhong, Xiao Wei, Zhao Lin-Guo
Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Nanjing Forestry University.
College of Chemical Engineering, Nanjing Forestry University.
Chem Pharm Bull (Tokyo). 2019;67(9):1006-1014. doi: 10.1248/cpb.c19-00366.
Chlorogenic acid (CGA) has been considered as one of important active components in a number of medicinal herbs. Recently our group demonstrated that caffeoyl salicylate scaffold derived from CGA can be employed for the development of novel anti-inflammatory agents. The most active compound D104 can be a very promising starting point for the further structural optimization. A series of novel caffeoyl salicylate analogs were designed, synthesized, and evaluated by preliminary biological evaluation. The obtained results showed that the two compounds B12 and B13 can not only inhibit production of nitric oxide (NO) in RAW264.7 cells induced by lipopolysaccharides (LPS) effectively, but also have high safety in in vitro cytotoxic test, which could be comparable with D104. Molecular docking study on the peroxisome proliferator-activated receptor γ (PPARγ) protein revealed that compounds B12 and B13 can follow the same binding mode with D104, and the carboxyl group of caffeoyl salicylate scaffold might play a key role in the interaction with protein target, which implied the carboxyl group should be retained in the further optimization.
绿原酸（CGA）被认为是多种草药中的重要活性成分之一。最近我们团队证明，源自CGA的咖啡酰水杨酸支架可用于开发新型抗炎药。活性最强的化合物D104可能是进一步结构优化的非常有前景的起点。设计、合成了一系列新型咖啡酰水杨酸类似物，并通过初步生物学评价进行了评估。所得结果表明，化合物B12和B13不仅能有效抑制脂多糖（LPS）诱导的RAW264.7细胞中一氧化氮（NO）的产生，而且在体外细胞毒性试验中具有高安全性，可与D104相媲美。对过氧化物酶体增殖物激活受体γ（PPARγ）蛋白的分子对接研究表明，化合物B12和B13与D104具有相同的结合模式，咖啡酰水杨酸支架的羧基在与蛋白质靶点的相互作用中可能起关键作用，这意味着在进一步优化中应保留羧基。
