Synthesis and evaluation of dihydropyrimidinone-derived selenoesters as multi-targeted directed compounds against Alzheimer’s disease
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- 作者：Flavio A.R. Barbosa ; Rô ; mulo F.S. Canto ; Sumbal Saba ; Jamal Rafique ; Antonio L. Braga ; braga.antonio@ufsc.br" class="auth_mail" title="E-mail the corresponding author
- 关键词：AD ; Alzheimer&rsquo ; s disease ; ROS ; reactive oxygen species ; AChE ; acetylcholinesterase ; DHPMs ; dihydropyrimidinones ; GPx ; glutathione peroxidase ; TBARS ; thiobarbituric acid reactive substances ; NMR ; nuclear magnetic resonance ; IR ; infrared spectroscopy ; HMRS ; high resolution mass spectrometry ; APPI ; atmosphere pressure photoionization ; DPDS ; diphenyl diselenide ; BHT ; butylated hydroxytoluene ; MDA ; malondialdehyde ; mp ; melting point
- 刊名：Bioorganic & Medicinal Chemistry
- 出版年：2016
- 出版时间：15 November 2016
- 年：2016
- 卷：24
- 期：22
- 页码：5762-5770
- 全文大小：934 K
文摘
This paper describes the synthesis and evaluation of new dihydropyrimidinone (DHPM)-derived selenoesters as potential multi-targeted agents for the treatment of Alzheimer’s disease. A series of DHPM-derived selenoesters were obtained with high structural diversity through a short and modular synthetic route. The antioxidant activity was evaluated by TBARS and iron chelation assays. These compounds were also evaluated as acetylcholinesterase inhibitors (AChEi). The compounds demonstrated good antioxidant activity, since they presented excellent lipid peroxidation inhibition and good iron chelation activity. In addition, they showed acetylcholinesterase inhibition activity and some of them presented activity superior to that of the standard drug galantamine. The in silico predictions showed that the compound 1h may present a good pharmacokinetic profile. Therefore, the series of DHPM-derived selenoesters described herein displayed good potential for the development of antioxidant and anticholinesterasic agents in the search for new multi-targeted therapeutics for the treatment of Alzheimer’s disease.