文献类型：期刊文献

英文题名：Design, synthesis and biological evaluation of novel osthole-based derivatives as potential neuroprotective agents

作者：Zhang, Li[1];Wu, Yuhang[1];Yang, Guixiang[1];Gan, Haixian[1];Sang, Dayong[2];Zhou, Jiye[1];Su, Lin[1];Wang, Rui[1];Ma, Lei[1]

机构：[1]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, 130 Meilong Rd, Shanghai 200237, Peoples R China;[2]Jingchu Univ Technol, Coll Chem Engn & Pharm, Jingmen 448000, Hubei, Peoples R China

年份：2020

卷号：30

期号：24

外文期刊名：BIOORGANIC & MEDICINAL CHEMISTRY LETTERS

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000595378800017)】；

基金：This work was supported by the National Natural Science Foundation of China (Grants 81973196 and 81673318), the 111 Project (Grant BP0719034) and the Natural Science Foundation of Shanghai, China (Grant 19ZR1413900).

语种：英文

外文关键词：Osthole; Neuroprotection; Antioxidant; Anti-inflammation; Amyloid beta-protein; Molecular docking

摘要：A total of 26 compounds based on osthole skeleton were designed, synthesized. Their cytoprotective abilities of antioxidation, anti-inflammation and A beta(42)(Amyloid beta-protein 42)-induced neurotoxicity were evaluated by MTT assays. Mechanism of the action of selected compounds were investigated by molecular docking. AlogP, logS and blood-brain barrier (BBB) permeability of all these compounds were simulated by admetSAR. Most of the compounds showed better antioxidative and anti-inflammatory activities compared with osthole, especially OST7 and OST17. The compound OST7 showed relative high activity in neuroprotection against H2O2 (45.7 +/- 5.5%), oxygen glucose deprivation (64.6 +/- 4.8%) and A beta(42) (61.4 +/- 5.2%) at a low concentration of 10 mu M. EC50 of selected compounds were measured in both H2O2 and OGD induced cytotoxicity models. Moreover, NO inhibiting ability of OST17(50.4 +/- 7.1%) already surpassed the positive drug indomethacin. The structure activity relationship study indicated that introduction of piperazine group, tetrahydropyrrole group and aromatic amine group might be beneficial for enhancement of osthole neuroprotective properties. Molecular docking explained that the reason OST7 exhibited relatively stronger neuroprotection against A beta because of the greater area of interactions between molecule and target protein. OST7 and OST17 both provided novel methods to investigate osthole as anti-AD drugs.