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Design, Synthesis and Biological Evaluation of Novel ( E )‐Hydroxystyryl Aralkyl Sulfones as Neuroprotective Agents
Author(s) -
Chen Ying,
Hao Yameng,
Liu Qian,
Wu Bolin,
Liu Yunqi,
Zhang Zhili,
Tian Chao,
Ning Xianling,
Guo Ying,
Wang Xiaowei,
Liu Junyi
Publication year - 2020
Publication title -
chemistryselect
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.437
H-Index - 34
ISSN - 2365-6549
DOI - 10.1002/slct.202001401
Subject(s) - neuroprotection , chemistry , nitric oxide , antioxidant , pharmacology , dpph , hydrogen peroxide , stereochemistry , biochemistry , organic chemistry , medicine
A novel class of ( E )‐hydroxystyryl aralkyl sulfones were designed and synthesized as neuroprotective agents. Their neuroprotective properties were assessed by several antioxidant models including 1,1‐diphenyl‐2‐picrylhydrazyl (DPPH) free radicals scavenging model, neuronal protective effects against neurotoxins such as hydrogen peroxide (H 2 O 2 ), 6‐hydroxydopamine (6‐OHDA) and 1‐methyl‐4‐phenylpyridinium iodide (MPP+). Besides, the anti‐inflammatory activity was evaluated by lipopolysaccharide (LPS)‐induced nitric oxide (NO) release model in BV2 microglial cells. The result demonstrated that cinnamyl substituted compound 5 h exhibited prominent antioxidant activity in H 2 O 2 and 6‐OHDA models and higher anti‐inflammatory potency (IC 50 =7.3 μM) than lead compound 1 (IC 50 =13.4 μM). Furthermore, compound 5 h displayed predicted CNS (+) blood‐brain barrier permeability ( P e =5.66×10 −6 cm s −1 ) in PAMPA model and low toxicity in PC12 and BV2 cells. These multifunctional properties highlight compound 5 h is a promising candidate for further development against neurodegenerative diseases.