Discovery of lipoic acid-4-phenyl-1H-pyrazole hybrids as novel bifunctional ROCK inhibitors with antioxidant activity

被引：6

作者：

Tu, Ya-lin ^{[1
,2
,3
]}

Chen, Qiu-he ^{[1
,2
,3
]}

Wang, Sheng-nan ^{[1
,2
,3
]}

Uri, Asko ^{[4
]}

Yang, Xiao-hong ^{[1
,2
,3
]}

Chu, Jia-qi ^{[1
,2
,3
]}

Chen, Jing-kao ^{[1
,2
,3
]}

Luo, Bing-ling ^{[2
,5
]}

Chen, Xiao-hong ^{[6
]}

Wen, Shi-jun ^{[2
,5
]}

Pi, Rong-biao ^{[1
,2
,3
,7
]}

机构：

[1] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China

[2] Int Joint Lab SYSU PolyU HK Novel Antidemenita Dr, Guangzhou 510006, Guangdong, Peoples R China

[3] Sun Yat Sen Univ, Nat & Local United Engn Lab Druggabil & New Drugs, Guangzhou, Guangdong, Peoples R China

[4] Univ Tartu, Inst Chem, Ravila St, EE-50411 Tartu, Estonia

[5] Sun Yat Sen Univ, Collaborat Innovat Ctr Canc Med, State Key Lab Oncol South China, Ctr Canc, 651 Dongfeng East Rd, Guangzhou 510060, Guangdong, Peoples R China

[6] Sun Yat Sen Univ, Dept Neurol, Affiliated Hosp 3, Guangzhou 510275, Guangdong, Peoples R China

[7] Sun Yat Sen Univ, Zhongshan Sch Med, Guangdong Prov Key Lab Brain Funct & Dis, Guangzhou 510080, Guangdong, Peoples R China

来源：

RSC ADVANCES | 2016年 / 6卷 / 63期

关键词：

RHO KINASE INHIBITORS; NERVOUS-SYSTEM DISORDERS; ALZHEIMERS-DISEASE; NEUROLOGICAL DISORDERS; OXIDATIVE STRESS; POTENT; ACID; FASUDIL; DESIGN; MODEL;

D O I：

10.1039/c6ra12081d

中图分类号：

O6 [化学];

学科分类号：

0703 ;

摘要：

A series of lipoic acid (LA) and 4-phenyl-1H-pyrazole hybrids as bifunctional Rho-associated kinase (ROCK) inhibitors were designed, synthesized and evaluated. Compound 15 is identified to be a novel potent bifunctional ROCK inhibitor with antioxidant activity and neuroprotection.

引用

页码：58516 / 58520

页数：5

共 31 条

[1]

Amigoni F, 2012, PHARM PAT ANAL, V1, P177, DOI [10.4155/ppa.12.19, 10.4155/PPA.12.19]

[2] Investigational drugs in Alzheimer's disease: current progress [J].

Berk, Camryn ;

Paul, Gaurav ;

Sabbagh, Marwan .

EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2014, 23 (06) :837-846

[3] Simply combining fasudil and lipoic acid in a novel multitargeted chemical entity potentially useful in central nervous system disorders [J].

Chen, Meihui ;

Liu, Qi ;

Liu, Anmin ;

Tan, Min ;

Xie, Zhiyong ;

Uri, Asko ;

Chen, Ziwei ;

Huang, Guangye ;

Sun, Yang ;

Ge, Hu ;

Liu, Peiqing ;

Li, Min ;

Li, Xingshu ;

Wen, Shijun ;

Pi, Rongbiao .

RSC ADVANCES, 2014, 4 (70) :37266-37269

[4] Fasudil and its analogs: a new powerful weapon in the long war against central nervous system disorders? [J].

Chen, Meihui ;

Liu, Anmin ;

Ouyang, Ying ;

Huang, Yingjuan ;

Chao, Xiaojuan ;

Pi, Rongbiao .

EXPERT OPINION ON INVESTIGATIONAL DRUGS, 2013, 22 (04) :537-550

[5] Chroman-3-amides as potent Rho kinase inhibitors [J].

Chen, Yen Ting ;

Bannister, Thomas D. ;

Weiser, Amiee ;

Griffin, Evelyn ;

Lin, Li ;

Ruiz, Claudia ;

Cameron, Michael D. ;

Schurer, Stephan ;

Duckett, Derek ;

Schroter, Thomas ;

LoGrasso, Philip ;

Feng, Yangbo .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2008, 18 (24) :6406-6409

[6] The Contributions Of Antioxidant Activity Of Lipoic Acid In Reducing Neurogenerative Progression Of Parkinson's Disease: A Review [J].

De Araujo, Dayane Pessoa ;

Guimaraes Lobato, Rodrigo De Freitas ;

Lopes De Paiva Cavalcanti, Jose Rodolfo ;

Leite Sampaio, Luis Rafael ;

Pontes Araujo, Paulo Victor ;

Chaves Silva, Marcia Calheiros ;

Tavares Neves, Kelly Rose ;

De Franca Fonteles, Marta Maria ;

Florenco De Sousa, Francisca Clea ;

Mendes Vasconcelos, Silvania Maria .

INTERNATIONAL JOURNAL OF NEUROSCIENCE, 2011, 121 (02) :51-57

[7] Strategy to reduce free radical species in Alzheimer's disease: an update of selected antioxidants [J].

Di Domenico, Fabio ;

Barone, Eugenio ;

Perluigi, Marzia ;

Butterfield, D. Allan .

EXPERT REVIEW OF NEUROTHERAPEUTICS, 2015, 15 (01) :19-40

[8] High throughput artificial membrane permeability assay for blood-brain barrier [J].

Di, L ;

Kerns, EH ;

Fan, K ;

McConnell, OJ ;

Carter, GT .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2003, 38 (03) :223-232

[9] L-Dopa- and dopamine-(R)-α-lipoic acid conjugates as multifunctional codrugs with antioxidant properties [J].

Di Stefano, A ;

Sozio, P ;

Cocco, A ;

Iannitelli, A ;

Santucci, E ;

Costa, M ;

Pecci, L ;

Nasuti, C ;

Cantalamessa, F ;

Pinnen, F .

JOURNAL OF MEDICINAL CHEMISTRY, 2006, 49 (04) :1486-1493

[10] Mild chronic cerebral hypoperfusion induces neurovascular dysfunction, triggering peripheral beta-amyloid brain entry and aggregation [J].

ElAli, Ayman ;

Theriault, Peter ;

Prefontaine, Paul ;

Rivest, Serge .

ACTA NEUROPATHOLOGICA COMMUNICATIONS, 2013, 1

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