European Journal of Medicinal Chemistry p. 420 - 433 (2019)
Update date:2022-08-05
Topics:
Chen, Ying
Wu, Bolin
Hao, Yameng
Liu, Yunqi
Zhang, Zhili
Tian, Chao
Ning, Xianling
Guo, Ying
Liu, Junyi
Wang, Xiaowei
(E)-3,4-dihydroxystyryl alkyl sulfones, as new analogues of neurodegenerative agents, were designed and synthesized. The biological results demonstrated that most of the target compounds preserved antioxidant and anti-inflammatory potency in scavenging reactive free radicals, protecting neuronal cells against neurotoxins such as H2O2, 6-hydroxydopamine and inhibiting lipopolysaccharide (LPS)-induced over-production of NO. Among these compounds, 6.22 with cyclopentyl propyl exhibited prominent antioxidant activity at low concentration (2.5 μM) in H2O2 model (cell viability = 94.5%). In addition, 6.22 (IC50 = 1.6 μM) displayed better anti-inflammatory activity than that of lead compound 1 (IC50 = 13.4 μM). In view of the outstanding performance of 6.22, the apoptotic rates of H2O2-damaged PC12 cells were detected by Annexin V-FITC/PI assay. 6.22 showed higher potency in inhibition of apoptosis than 1 at low concentration (2.5 μM), consisting with the antioxidant and anti-inflammatory models. Furthermore, with the predicted CNS (+) blood-brain barrier (BBB) permeability (Pe = 6.84 × 10?6 cm s?1), low cytotoxicity and favorable physiochemical properties based on calculation, compound 6.22 can be further developed as a potential multifunctional neuroprotective agent.
View MoreVanderArk International Limited
Contact:86-10-82437576
Address:Qing He
Taizhou Huading Chemical Co.,Ltd
Contact:+86-576-88583898
Address:Economic&Technology development zone,Taizhou City,Zhejiang Province,China
Yangzhou Zhongbao Pharmaceutical Co.,Ltd
Contact:+86-514-88290838
Address:Jiangsu Baoying county economic develpment zone in baoying avenue91
Shanghai ZaiQi Bio-Tech Co., Ltd.,
Contact:+86-21-6722 0633
Address:Bldg. No.7, No.201 MinYi Rd,Songjiang CaoHeJing High-Tech Park Shanghai 201516 P,R,China
Dezhou Longteng Chemical Co., Ltd.
website:http://www.sodium-methoxide.cn/
Contact:0086-18866052283
Address:Xinhua Industrial Zone, Dezhou City, Shandong Province, China
Doi:10.1016/j.ejmech.2018.11.033
(2019)Doi:10.1055/s-0034-1380754
(2015)Doi:10.1002/chem.200401116
(2005)Doi:10.1016/j.tetlet.2005.03.143
(2005)Doi:10.1021/op200171a
(2011)Doi:10.1016/j.bmcl.2005.02.090
(2005)