SAR, cardiac myocytes protection activity and 3D-QSAR studies of salubrinal and its potent derivatives

Current Medicinal Chemistry

Volumn 19, Issue 35, 2012, Pages 6072-6079

  Liu, J ^a,b   He, K L ^c   Li, X ^c   Li, R J ^b   Liu, C L ^b   Zhong, W ^b   Li, S ^b  

^a SHENYANG PHARMACEUTICAL UNIVERSITY   (China)

^b BEIJING INSTITUTE OF PHARMACOLOGY AND TOXICOLOGY   (China)

^c CHINESE PLA GENERAL HOSPITAL   (China)

Author keywords

Cardiomyocytes protection; CoMFA model; Endoplasmic reticulum (ER) stress; Eukaryotic translation initiation factor 2 subunit (eIF2 ) phosphorylation; MTT; PP1 GADD34 complex inhibitor; Predicted abilities; Salubrinal; Structure activity relationships (SAR); UPR

Indexed keywords

3 (FURAN 2 YL) N (2,2,2 TRICHLORO 1 CINNAMAMIDOETHYL)ACRYLAMIDE; 3 (PYRIDIN 4 YL) N (2,2,2 TRICHLORO 1 CINNAMAMIDOETHYL)ACRYLAMIDE; 3 (THIOPHEN 2 YL) N [2,2,2 TRICHLORO 1 (3 BENZYLTHIOUREIDO)ETHYL]ACRYLAMIDE; 3 (THIOPHEN 2 YL) N [2,2,2 TRICHLORO 1 (3 CYCLOHEPTYLTHIOUREIDO)ETHYL]ACRYLAMIDE; 3 (THIOPHEN 2 YL) N [2,2,2 TRICHLORO 1 (3 CYCLOHEXYLTHIOUREIDO)ETHYL]ACRYLAMIDE; 3 (THIOPHEN 2 YL) N [2,2,2 TRICHLORO 1 (3 QUINOLIN 8 YLTHIOUREIDO)ETHYL]ACRYLAMIDE; 3 (THIOPHEN 2 YL) N [2,2,2 TRICHLORO 1 [3 (2 FLUOROPHENYL)THIOUREIDO]ETHYL]ACRYLAMIDE; 3 (THIOPHEN 2 YL) N [2,2,2 TRICHLORO 1 [3 (2 METHOXYCARBONYLPHENYL)THIOUREIDO]ETHYL]ACRYLAMIDE; 3 (THIOPHEN 2 YL) N [2,2,2 TRICHLORO 1 [3 (2 METHOXYPHENYL)THIOUREIDO]ETHYL]ACRYLAMIDE; 3 (THIOPHEN 2 YL) N [2,2,2 TRICHLORO 1 [3 (3 ISOPROPOXYLPROPYL)THIOUREIDO]ETHYL]ACRYLAMIDE; 3 (THIOPHEN 2 YL) N [2,2,2 TRICHLORO 1 [3 (4 METHYLPHENYL)THIOUREIDO]ETHYL]ACRYLAMIDE; N [2,2,2 TRICHLORO 1 (3 MORPHOLIN 1 YLTHIOUREIDO)ETHYL]CINNAMAMIDE; N [2,2,2 TRICHLORO 1 (3 QUINOLIN 8 YLUREIDO)ETHYL]CINNAMAMIDE; N [2,2,2 TRICHLORO 1 (3,4 TOLYLUREIDO)ETHYL]CINNAMAMIDE; N [2,2,2 TRICHLORO 1 (4 PHENYLTHIAZOL 2 YLAMINO)ETHYL]CINNAMAMIDE; N [2,2,2 TRICHLORO 1 [3 (2 CHLOROPHENYL)THIOUREIDO]ETHYL]CINNAMAMIDE; N [2,2,2 TRICHLORO 1 [3 (2 CHLOROPHENYL)UREIDO]ETHYL]CINNAMAMIDE; N [2,2,2 TRICHLORO 1 [3 (2 METHOXYPHENYL)UREIDO]ETHYL]CINNAMAMIDE; N [2,2,2 TRICHLORO 1 [3 (2,3 BIMETHYL)PHENYLTHIOUREIDO]ETHYL]CINNAMAMIDE; N [2,2,2 TRICHLORO 1 [3 (4 METHOXYBENZYL)THIOUREIDO]ETHYL]CINNAMAMIDE; N [2,2,2 TRICHLORO 1 [3 (4 METHYLPHENYL)THIOUREIDO]ETHYL]CINNAMAMIDE; N [2,2,2 TRICHLORO 1 [3 (4 METHYLPIPERAZIN 1 YL)THIOUREIDO]ETHYL]CINNAMAMIDE; N [2,2,2 TRICHLORO 1 [4 (2,4 BIFLUOROPHENYL)THIAZOL 2 YLAMINO]ETHYL]CINNAMAMIDE; N [2,2,2 TRICHLORO 1 [4 (4 CHLOROPHENYL)THIAZOL 2 YLAMINO]ETHYL]CINNAMAMIDE; N [2,2,2 TRICHLORO 1 [4 (4 METHOXYPHENYL) 5 PHENYLTHIAZOL 2 YLAMINO]ETHYL]CINNAMAMIDE; N [2,2,2 TRICHLORO 1 [4 (4 METHOXYPHENYL)THIAZOL 2 YLAMINO]ETHYL]CINNAMAMIDE; PP 11; PP 110; PP 111; PP 112; PP 113; PP 114; PP 115; PP 116; PP 118; PP 119; PP 120; PP 121; PP 122; PP 123; PP 124; PP 125; PP 126; PP 14; PP 15; PP 17; PP 18; PP 19; SALUBRINAL; UNCLASSIFIED DRUG;

ANIMAL CELL; ARTICLE; CELL ACTIVITY; COMPARATIVE MOLECULAR FIELD ANALYSIS; DRUG POTENCY; HEART MUSCLE CELL; HEART PROTECTION; NONHUMAN; QUANTITATIVE STRUCTURE ACTIVITY RELATION; RAT; STRUCTURE ACTIVITY RELATION;

ANIMALS; CARDIOTONIC AGENTS; CELLS, CULTURED; CINNAMATES; EIF-2 KINASE; ENDOPLASMIC RETICULUM STRESS; MYOCYTES, CARDIAC; PHOSPHORYLATION; QUANTITATIVE STRUCTURE-ACTIVITY RELATIONSHIP; RATS; THIAZOLES; THIOUREA;

EID: 84871293240     PISSN: 09298673     EISSN: 1875533X     Source Type: Journal    
DOI: 10.2174/092986712804485971     Document Type: Article

References (18)

1. Thuerauf, D. J.; Marcinko, M.; Gude, N.; Rubio, M.; Sussman, M. A.; Glembotski, C. C. Activation of the unfolded protein response in infarcted mouse heart and hypoxic cultured cardiac myocytes. Circ. Res., 2006, 99, 275-282
2. Sundar Rajan, S.; Srinivasan, V.; Balasubramanyam, M. Endoplasmic reticulum (ER) stress & diabetes. Indian J. Med. Res., 2007, 125, 411-424
3. Schröder, M. Endop lasmic reticulum stress responses. Cell Mol. Life Sci. 2008, 65, 862-894.
4. Glembotski, C. C. Endoplasmic Reticulum Stress in the Heart. Circ. Res., 2007, 101, 975-984
5. Boyce, M.; Bryant, K.; Jousse, C.; Long, K.; Harding, H. P.; Scheuner, D.; Kaufman, R. J.; Ma, D.; Coen, D. M.; Ron, D.; Yuan, J. A Selective Inhibitor of eIF2α Dephosphorylation Protects Cells from ER Stress. Science, 2005, 307, 935-939
6. Lee, D. Y.; Lee, K. S.; Lee, H. J.; Kim, D. H.; Noh, Y. H.; Yu, K.; Jung, H. Y.; Lee, S. H.; Lee, J. Y.; Youn, Y. C.; Jeong, Y.; Kim, D. K.; Lee, W. B.; Kim, S. S. Activation of PERK signaling attenuates Abeta-mediated ER stress. PLoS One, 2010, 5, e10489
7. Komoike, Y.; Inamura, H.; Matsuoka, M. Effects of salubrinal on cadmiuminduced apoptosis in HK-2 human renal proximal tubular cells. Arch. Toxicol, 2012, 86, 37-44
8. Li, L.; Hu, B. C.; Gong, S. J.; Yan, J. Homocysteine-induced caspase-3 activation by endoplasmic reticulum stress in endothelial progenitor cells from patients with coronary heart disease and healthy donors. Biosci. Biotechnol. Biochem., 2011, 75, 1300-1305
9. Cnop, M.; Ladriere, L.; Hekerman, P.; Ortis, F.; Cardozo, A. K.; Dogusan, Z.; Flamez, D.; Boyce, M.; Yuan, J.; Eizirik, D. L. Selective Inhibition of Eukaryotic Translation Initiation Factor 2α Dephosphorylation Potentiates Fatty Acid-induced Endoplasmic Reticulum Stress and Causes Pancreatic β-Cell Dysfunction and Apoptosis. J. Biol. Chem., 2007, 282, 3989-3997
10. Wu, C. T.; Sheu, M. L.; Tsai, K. S.; Chiang, C. K.; Liu, S. H. Salubrinal, an eIF2α dephosphorylation inhibitor, enhances cisplatin-induced oxidative stress and nephrotoxicity in a mouse model. Free Radic. Biol. Med., 2011, 51, 671-680
11. Park, G. B.; Kim, Y. S.; Lee, H. K.; Song, H.; Cho, D. H.; Lee, W. J.; Hur, D. Y. Endoplasmic reticulum stress-mediated apoptosis of EBV-transformed B cells by cross-linking of CD70 is dependent upon generation of reactive oxygen species and activation of p38 MAPK and JNK pathway. J. Immunol, 2010, 185, 7274-7284
12. Long, K.; Boyce, M.; Lin, H.; Yuan, J.; Ma, D. Structure-activity relationship studies of salubrinal lead to its active biotinylated derivative. Bioorg. Med. Chem. Lett, 2005, 15, 3849-3852
13. Costa-Mattioli, M.; Gobert, D.; Stern, E.; Gamache, K.; Colina, R.; Cuello, C.; Sossin, W.; Kaufman, R.; Pelletier, J.; Rosenblum, K.; Krnjevic, K.; Lacaille, J. C.; Nader, K.; Sonenberg, N. eIF2α phosphorylation bidirectionally regulates the switch from short-to long-term synaptic plasticity and memory. Cell, 2007, 129, 195-206
14. Nickson, P.; Toth, A.; Erhardt, P. PUMA is critical for neonatal cardiomyocyte apoptosis induced by endoplasmic reticulum stress. Cardiovasc. Res., 2007, 73, 48-56
15. Zhang, Y.; Ren, J. Thapsigargin triggers cardiac contractile dysfunction via NADPH oxidase-mediated mitochondrial dysfunction: Role of Akt dephosphorylation. Free Radic. Biol. Med., 2011, 51, 2172-2184
16. Yamaguchi, H.; Wang, H.-G. CHOP Is Involved in Endoplasmic Reticulum Stress-induced Apoptosis by Enhancing DR5 Expression in Human Carcinoma Cells. J. Biol. Chem., 2004, 279, 45495-45502
17. Gupta, P.; Garg, P.; Roy, N. Comparative docking and CoMFA analysis of curcumine derivatives as HIV-1 integrase inhibitors. Mol. Divers., 2011, 15, 733-750
18. Deswal, S.; Roy, N. A novel range based QSAR study of human neuropeptide Y (NPY) Y5 receptor inhibitors. Eur. J. Med. Chem., 2007, 42, 463-470.