A Potent (R)-alpha-bis-lipoyl Derivative Containing 8-Hydroxyquinoline Scaffold: Synthesis and Biological Evaluation of Its Neuroprotective Capabilities in SH-SY5Y Human Neuroblastoma Cells

被引：25
作者：
Cacciatore, Ivana [1 ]
Fornasari, Erika [1 ]
Baldassarre, Leonardo [1 ]
Cornacchia, Catia [1 ]
Fulle, Stefania [2 ,3 ]
Di Filippo, Ester Sara [2 ,3 ]
Pietrangelo, Tiziana [2 ,3 ]
Pinnen, Francesco [1 ]
机构：
[1] Univ G DAnnunzio, Dipartimento Farm, Via Vestini 31, I-66100 Chieti, Italy
[2] Univ G DAnnunzio, Dipartimento Neurosci & Imaging, IIM, I-66100 Chieti, Italy
[3] Fdn Dannunzio, CeSI Ctr Studi Invecchiamento, I-66100 Chieti, Italy
来源：
PHARMACEUTICALS | 2013年 / 6卷 / 01期
关键词：
(R)-alpha-lipoic acid; 8-hydroxyquinoline; neuroprotective agent; antioxidants; neurodegenerative diseases;
D O I：
10.3390/ph6010054
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
A novel bis-lipoyl derivative containing 8-hydroxyquinoline scaffold (LA-HQ-LA, 5) was synthesized as a new multifunctional drug candidate with antioxidant, chelant, and neuroprotective properties for the treatment of neurodegenerative diseases. We have investigated the potential effectiveness of LA-HQ-LA against the cytotoxicity induced by 6-OHDA and H(2)O(2 )on human neuroblastoma SH-SY5Y cell line. Our outcomes showed that LA-HQ-LA resulted in significant neuroprotective and antioxidant effects against H2O2- and 6-OHDA-induced neurotoxicity in human neuroblastoma SH-SY5Y cells, as assessed by MTT assay. In particular, it showed potent neuroprotective effects against 6-OHDA in RA/PMA differentiated cells at all the tested concentrations.
引用
收藏
页码：54 / 69
页数：16
相关论文
共 40 条
[1]   Neuroprotection by a novel brain permeable iron chelator, VK-28, against 6-hydroxydopamine lession in rats [J].
Ben Shachar, D ;
Kahana, N ;
Kampel, V ;
Warshawsky, A ;
Youdim, MBH .
NEUROPHARMACOLOGY, 2004, 46 (02) :254-263
[2]   The concept of privileged structures in rational drug design: focus on acridine and quinoline scaffolds in neurodegenerative and protozoan diseases [J].
Bongarzone, Salvatore ;
Bolognesi, Maria Laura .
EXPERT OPINION ON DRUG DISCOVERY, 2011, 6 (03) :251-268
[3]   Metals and neuroscience [J].
Bush, AI .
CURRENT OPINION IN CHEMICAL BIOLOGY, 2000, 4 (02) :184-191
[4]   GPE and GPE Analogues as Promising Neuroprotective Agents [J].
Cacciatore, I. ;
Cornacchia, C. ;
Baldassarre, L. ;
Fornasari, E. ;
Mollica, A. ;
Stefanucci, A. ;
Pinnen, F. .
MINI-REVIEWS IN MEDICINAL CHEMISTRY, 2012, 12 (01) :13-23
[5]   (R)-α-Lipoyl-Glycyl-L-Prolyl-L-Glutamyl Dimethyl Ester Codrug as a Multifunctional Agent with Potential Neuroprotective Activities [J].
Cacciatore, Ivana ;
Baldassarre, Leonardo ;
Fornasari, Erika ;
Cornacchia, Catia ;
Di Stefano, Antonio ;
Sozio, Piera ;
Cerasa, Laura Serafina ;
Fontana, Antonella ;
Fulle, Stefania ;
Di Filippo, Ester Sara ;
La Rovere, Rita Maria Laura ;
Pinnen, Francesco .
CHEMMEDCHEM, 2012, 7 (11) :2021-2029
[6]   Recent Advances in the Treatment of Neurodegenerative Diseases Based on GSH Delivery Systems [J].
Cacciatore, Ivana ;
Baldassarre, Leonardo ;
Fornasari, Erika ;
Mollica, Adriano ;
Pinnen, Francesco .
OXIDATIVE MEDICINE AND CELLULAR LONGEVITY, 2012, 2012
[7]   Prodrug Approach for Increasing Cellular Glutathione Levels [J].
Cacciatore, Ivana ;
Cornacchia, Catia ;
Pinnen, Francesco ;
Mollica, Adriano ;
Di Stefano, Antonio .
MOLECULES, 2010, 15 (03) :1242-1264
[8]   2,5-Diketopiperazines as Neuroprotective Agents [J].
Cornacchia, C. ;
Cacciatore, I. ;
Baldassarre, L. ;
Mollica, A. ;
Feliciani, F. ;
Pinnen, F. .
MINI-REVIEWS IN MEDICINAL CHEMISTRY, 2012, 12 (01) :2-12
[9]   Metal based neurodegenerative diseases - From molecular mechanisms to therapeutic strategies [J].
Crichton, Robert R. ;
Dexter, D. T. ;
Ward, Roberta J. .
COORDINATION CHEMISTRY REVIEWS, 2008, 252 (10-11) :1189-1199
[10]  
Cuajungco MP, 2000, ANN NY ACAD SCI, V920, P292
1234