Design, synthesis, and biological activity evaluation of BACE1 inhibitors with antioxidant activity

被引：8

作者：

Li, He-Min ^{[1
]}

Yu, Shao-Peng ^{[1
]}

Fan, Yuan ^{[1
]}

Zhong, Yue ^{[1
]}

Gu, Ting ^{[1
]}

Wu, Wen-Yu ^{[1
]}

Zhao, Chao ^{[1
]}

Chen, Zhi ^{[1
]}

Chen, Min ^{[1
]}

Li, Nian-Guang ^{[1
]}

Wang, Xiao-Long ^{[1
]}

机构：

[1] Nanjing Univ Chinese Med, Dept Med Chem, Nanjing 210023, Jiangsu, Peoples R China

来源：

DRUG DEVELOPMENT RESEARCH | 2020年 / 81卷 / 02期

关键词：

Alzheimer's disease; antioxidant activity; BACE1; molecular docking; molecular hybridization; BETA-SECRETASE INHIBITORS; ALZHEIMERS-DISEASE; DERIVATIVES; ACIDS;

D O I：

10.1002/ddr.21585

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The proteolytic enzyme beta-secretase (BACE1) plays a central role in the synthesis of the pathogenic beta-amyloid peptides (A beta) in Alzheimer's disease (AD), antioxidants could attenuate the AD syndrome and prevent the disease progression. In this study, BACE1 inhibitors (D1-D18) with free radical-scavenging activities were synthesized by molecular hybridization of 2-aminopyridine with natural antioxidants. The biological activity evaluation showed that D1 had obvious inhibitory activity against BACE1, and strong antioxidant activity in 1,1-diphenyl-2-picrylhydrazyl (DPPH) and 2,2 '-azinobis-(3-ethylbenzthiazoline-6-sulphonate) (ABTS(+center dot)) assay, which could be used as a lead compound for further study.

引用

页码：206 / 214

页数：9

共 50 条

[41] A stereoselective approach to peptidomimetic BACE1 inhibitors
Butini, Stefania
Gabellieri, Emanuele
Brindisi, Margherita
Giovani, Simone
Maramai, Samuele
Kshirsagar, Giridhar
Guarino, Egeria
Brogi, Simone
La Pietra, Valeria
Giustiniano, Mariateresa
Marinelli, Luciana
Novellino, Ettore
Campiani, Giuseppe
Cappelli, Andrea
Gemma, Sandra
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2013, 70 : 233 - 247
[42] Discovery of potent iminoheterocycle BACE1 inhibitors
Caldwell, John P.
Mazzola, Robert D.
Durkin, James
Chen, Joseph
Chen, Xia
Favreau, Leonard
Kennedy, Matthew
Kuvelkar, Reshma
Lee, Julie
McHugh, Nansie
McKittrick, Brian
Orth, Peter
Stamford, Andrew
Strickland, Corey
Voigt, Johannes
Wang, Liyang
Zhang, Lili
Zhang, Qi
Zhu, Zhaoning
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2014, 24 (23) : 5455 - 5459
[43] Synthesis of morpholine derivatives using the Castagnoli-Cushman reaction as BACE1 inhibitors: Unexpected binding activity of cyclic thioamides
Calugi, Lorenzo
Lenci, Elena
Innocenti, Riccardo
Trabocchi, Andrea
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2020, 30 (13)
[44] Plant phenolics as β-secretase (BACE1) inhibitors
Jun, Mira
Lee, Seung-Ho
Choi, Sun-Ha
Bae, KiHwan
Seong, Yeon-Hee
Lee, Kyung-Bok
Song, Kyung-Sik
FOOD SCIENCE AND BIOTECHNOLOGY, 2006, 15 (04) : 617 - 624
[45] Discovery of imidazopyridines containing isoindoline-1,3-dione framework as a new class of BACE1 inhibitors: Design, synthesis and SAR analysis
Azimi, Sara
Zonouzi, Afsaneh
Firuzi, Omidreza
Iraji, Aida
Saeedi, Mina
Mahdavi, Mohammad
Edraki, Najmeh
EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2017, 138 : 729 - 737
[46] Design, Synthesis, and Biological Evaluation of Notopterol Derivatives as Triple Inhibitors of AChE/BACE1/GSK3β for the Treatment of Alzheimer's Disease
Wang, Nan
Liu, Wenjie
Zhou, Lijun
Liu, Wenwu
Liang, Xu
Liu, Xin
Xu, Zihua
Zhong, Tianming
Wu, Qiong
Jiao, Xinming
Chen, Jiangxia
Ning, Xinyue
Jiang, Xiaowen
Zhao, Qingchun
ACS OMEGA, 2022, 7 (36): : 32131 - 32152
[47] Design, Synthesis, and Biological Evaluation of Notopterol Derivatives as Triple Inhibitors of AChE/BACE1/GSK3β for the Treatment of Alzheimer's Disease
Wang, Nan
Liu, Wenjie
Zhou, Lijun
Liu, Wenwu
Liang, Xu
Liu, Xin
Xu, Zihua
Zhong, Tianming
Wu, Qiong
Jiao, Xinming
Chen, Jiangxia
Ning, Xinyue
Jiang, Xiaowen
Zhao, Qingchun
ACS OMEGA, 2023, 8 (01): : 1722 - 1722
[48] Tripeptidic BACE1 inhibitors devised by in-silico conformational structure-based design
Hamada, Yoshio
Tagad, Harichandra D.
Nishimura, Yoshinori
Ishiura, Shoichi
Kiso, Yoshiaki
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2012, 22 (02) : 1130 - 1135
[49] Design and synthesis of aminohydantoins as potent and selective human β-secretase (BACE1) inhibitors with enhanced brain permeability
Malamas, Michael S.
Robichaud, Albert
Erdei, Jim
Quagliato, Dominick
Solvibile, William
Zhou, Ping
Morris, Koi
Turner, Jim
Wagner, Erik
Fan, Kristi
Olland, Andrea
Jacobsen, Steve
Reinhart, Peter
Riddell, David
Pangalos, Menelas
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2010, 20 (22) : 6597 - 6605
[50] Sulfonamido-derivatives of unsubstituted carbazoles as BACE1 inhibitors
Bertini, Simone
Ghilardi, Elisa
Asso, Valentina
Minutolo, Filippo
Rapposelli, Simona
Digiacomo, Maria
Saccomanni, Giuseppe
Salmaso, Veronica
Sturlese, Mattia
Moro, Stefano
Macchia, Marco
Manera, Clementina
BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2017, 27 (21) : 4812 - 4816

← 1 2 3 4 5 →