Design, synthesis, and biological evaluation of (e)-3,4-dihydroxystyryl aralkyl sulfones and sulfoxides as novel multifunctional neuroprotective agents.
Novel (E)-3,4-dihydroxystyryl aralkyl sulfones and sulfoxides were designed and synthesized as new analogues of 1, which showed interesting multifunctional neuroprotective effects, including antioxidative and antineuroinflammatory properties. Specifically, target compounds display excellent potency in scavenging reactive free radicals and demonstrate potent effects against various kinds of toxicities, including H2O2, 6-hydroxydopamine, and lipopolysaccharide in different types of neuronal cells. The antioxidative properties of the target compounds are more potent than that of 1, and the antineuroinflammatory properties are less strong than that of 1. According to the parallel artificial membrane permeation assay for the blood-brain barrier, target compounds possess greater blood-brain barrier (BBB) permeability than 1. In short, due to improvement of the antioxidative effect, stability, and BBB permeability, (E)-3,4-dihydroxystyryl aralkyl sulfones and sulfoxides can thus be considered as potential multifunctional neuroprotective agents and serve as new lead candidates in the treatment of neurodegenerative diseases.
Department of Chemical Biology, School of Pharmaceutical Sciences, ‡State Key Laboratory of Natural and Biomimetic Drugs, and §Department of the Integration of Chinese and Western Medicine, School of Basic Medical Sciences, Peking University , Beijing 100191, China.
Xianling
X
Ning
Ying
Y
Guo
Xiaowei
X
Wang
Xiaoyan
X
Ma
Chao
C
Tian
Xueqi
X
Shi
Renzong
R
Zhu
Can
C
Cheng
Yansheng
Y
Du
Zhizhong
Z
Ma
Zhili
Z
Zhang
Junyi
J
Liu
D000818:Animals; D001812:Blood-Brain Barrier; D015195:Drug Design; D016166:Free Radical Scavengers / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology; D009569:Nitric Oxide / Q000037:antagonists & inhibitors; D016627:Oxidopamine; D016716:PC12 Cells; D051381:Rats; D013450:Sulfones / Q000138:chemical synthesis* / Q000494:pharmacology; D013454:Sulfoxides / Q000138:chemical synthesis* / Q000494:pharmacology
D016166:Free Radical Scavengers; D018696:Neuroprotective Agents; D013450:Sulfones; D013454:Sulfoxides; D009569:Nitric Oxide; D016627:Oxidopamine