神经保护
化学
药理学
神经毒性
哌嗪
细胞毒性
EC50型
对接(动物)
血脑屏障
立体化学
抗氧化剂
MTT法
体外
生物化学
毒性
有机化学
中枢神经系统
神经科学
护理部
生物
医学
作者
Li Zhang,Yuhang Wu,Guixiang Yang,Haixian Gan,Dayong Sang,Jiye Zhou,Lin Lin Su,Rong Wang,Lei Ma
标识
DOI:10.1016/j.bmcl.2020.127633
摘要
A total of 26 compounds based on osthole skeleton were designed, synthesized. Their cytoprotective abilities of antioxidation, anti-inflammation and Aβ42(Amyloid β-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 Aβ42 (61.4 ± 5.2%) at a low concentration of 10 μM. 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 Aβ 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.
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