Synthesis and in vitro evaluation of sulfonamide isatin Michael acceptors as small molecule inhibitors of caspase-6

Journal of Medicinal Chemistry

Volumn 52, Issue 8, 2009, Pages 2188-2191

  Chu, Wenhua ^a   Rothfuss, Justin ^a   Chu, Yunxiang ^a   Zhou, Dong ^a   Mach, Robert H ^a  

^a WASHINGTON UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AZETIDINE DERIVATIVE; CASPASE 3; CASPASE 6; CASPASE INHIBITOR; HUNTINGTIN; ISATIN DERIVATIVE; ISATIN MICHAEL ACCEPTOR DERIVATIVE; MORPHOLINE DERIVATIVE; PYRROLIDINE DERIVATIVE; SULFONAMIDE; THIOMORPHOLINE DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG POTENCY; DRUG SCREENING; DRUG SELECTIVITY; DRUG STRUCTURE; DRUG SYNTHESIS; DRUG TARGETING; ENZYME ASSAY; ENZYME INHIBITION; ENZYME MECHANISM; HUMAN; HUNTINGTON CHOREA; IC 50; IN VITRO STUDY; MOLECULAR SIZE;

CASPASE 3; CASPASE 6; HUMANS; ISATIN; RECOMBINANT PROTEINS; STRUCTURE-ACTIVITY RELATIONSHIP; SULFONAMIDES;

EID: 65249096525     PISSN: 00222623     EISSN: None     Source Type: Journal    
DOI: 10.1021/jm900135r     Document Type: Article

References (31)

1. Honig, L. S.; Rosenberg, R. N. Apoptosis and neurologic disease. Am. J. Med. 2000, 108, 317-330.
2. Ventimiglia, R.; Lau, L. F.; Kinloch, R. A.; Hopkins, A; Karran, E. H.; Pet al.idis, L. P.; Ward, R. V. Role of caspases in neuronal apoptosis. Drug Dev. Res. 2001, 52, 515-533.
3. Robertson, G. S.; Crocker, S. J.; Nicholson, D. W.; Schulz, J. B. Neuroprotection by the inhibition of apoptosis. Brain Pathol. 2000, 10, 283-292.
4. Thornberry, N. A.; Lazebnik, Y. Caspases: enemies within. Science 1998, 281, 1312-1316.
5. Earnshaw, W. C.; Martins, L. M.; Kaufmann, S. H. Mammalian caspases: structure, activation, substrates and functions during apoptosis. Annu. Rev. Biochem. 1999, 68, 383-424.
6. Nicholson, D. W.; Thornberry, N. A. Caspases: killer proteases. Trends Biochem. Sci. 1997, 22, 299-306.
7. Guo, H.; Albrecht, S.; Bourdeau, M.; Petzke, T.; Bergeron, C.; LeBlanc, A. C. Active caspase-6 and caspase-6-cleaved tau in neuropil threads, neuritic plaques, and neurofibrillary tangles of Alzheimer's disease. Am. J. Pathol. 2004, 165, 523-531.
8. LeBlanc, A.; Liu, H.; Goodyer, C.; Bergeron, C.; Hammond, J. Caspase-6 role in apoptosis of human neurons, amyloidogenesis, and Alzheimer's disease. J. Biol. Chem. 1999, 23426-23436.
9. Klaiman, G.; Petzke, T. L.; Hammond, J.; LeBlanc, A. C. Targets of caspase-6 activity in human neurons and Alzheimer disease. Mol. Cell. Proteomics 2008, 7, 1541-1555.
10. Horowitz, P. M.; Patterson, K. R.; Guillozet-Bongaarts, A. L.; Reynolds, M. R.; Carroll, C. A.; Weintraub, S. T.; Bennett, D. A.; Cryns, V. L.; Berry, R. W.; Binder, L. I. Early N-terminal changes and caspase-6 cleavage of tau in Alzheimer's disease. J. Neurosci. 2004, 24, 7895-7902.
11. Warby, S. C.; Doty, C. N.; Graham, R. K.; Carroll, J. B.; Yang, Y. Z.; Singaraja, R. R.; Overall, C. M.; Hayden, M. R. Activated caspase-6 and caspase-6-cleaved fragments of huntingtin specifically colocalize in the nucleus. Hum. Mol. Genet. 2008, 17, 2390-2404.
12. Fryer, J. D.; Zoghbi, H. Y. Huntingtin's critical cleavage. Nat. Neurosci. 2006, 9, 1088-1089.
13. Gervais, F. G.; Xu, D.; Robertson, G. S.; Vaillancourt, J. P.; Zhu, Y.; Huang, J.; LeBlanc, A.; Smith, D.; Rigby, M.; Shearman, M. S.; et al. Involvement of caspases in proteolytic cleavage of Alzheimer's amyloid-β precursor protein and amyloidogenic Aβ peptide formation. Cell 1999, 97, 395-406.
14. Albrecht, S.; Bourdeau, M.; Bennett, D.; Mufson, E. J.; Bhattacharjee, M.; LeBlanc, A. C. Activation of caspase-6 in aging and mild cognitive impairment. Am. J. Pathol. 2007, 170, 1200-1209.
15. Wellington, C. L.; Singaraja, R.; Ellerby, L.; Savill, J.; Roy, S.; Leavitt, B.; Cattaneo, E.; Hackam, A.; Sharp, A.; Thornberry, N.; et al. Inhibiting caspase cleavage of huntingtin reduces toxicity and aggregate formation in neuronal and nonneuronal cells. J. Biol. Chem. 2000, 275, 19831-19838.
16. Graham, R. K.; Deng, Y.; Slow, E. J.; Haigh, B.; Bissada, N.; Lu, G.; Pearson, J.; Shehadeh, J.; Bertram, L.; Murphy, Z.; et al. Cleavage at the caspase-6 site is required for neuronal dysfunction and degeneration due to mutant huntingtin. Cell 2006, 125, 1179-1191.
17. (a) Otto, H. H.; Schirmeister, T. Cysteine proteases and their inhibitors. Chem. Rev. 1997, 97, 133-171.
18. (b) Powers, J. C.; Asgian, J. L.; Ekici, Z. D.; James, K. E. Chem. Rev. 2002, 102, 4639-4750.
19. (a) Talanian, R. V.; Brady, K. D.; Cryns, V. L. Caspases as targets for anti-inflammatory and anti-apoptotic drug discovery. J. Med. Chem. 2000, 43, 3351-3371.
20. (b) James, K. E.; Asgian, J. L.; Li, Z. Z.; Ekici, Z. D.; Rubin, J. R.; Mikolajczyk, J.; Salvesen, G. S.; Powers, J. C. Design, synthesis, and evaluation of aza-peptide epoxides as selective and potent inhibitors of caspase-1, -3, -6, and -8. J. Med. Chem. 2004, 47, 1553-1574.
21. (c) Ekici, Z. D.; Li, Z. Z.; Campbell, A. J.; James, K. E.; Asgian, J. L.; Mikolajczyk, J.; Salvesen, G. S.; Ganesan, R. G.; Jelakovic, S.; Grutter, M. G.; Powers, J. C. Design, synthesis, and evaluation of aza-peptide Mchael acceptors as selective and potent inhibitors of caspase-2, -3, -6, -7, -8, -9, and -10. J. Med. Chem. 2006, 49, 5728-5749.
22. (a) Nyormoi, O.; Wang, Z.; Bar-Eli, M. Sequence-based discovery of a synthetic peptide inhibitor of caspase-6. Apoptosis 2003, 8, 371-376.
23. (b) Wolf, B. B.; Green, D. R. Suicidal tendencies: apoptotic cell death by caspase family proteinases. J. Biol. Chem. 1999, 274, 20049-20052.
24. (c) Talanian, R. V.; Quinlan, C.; Trautz, S.; Hachett, M. C.; Mankovich, J. A.; Banach, D.; Ghayur, T.; Brady, K. D.; Wong, W. W. Substrate specificities of caspase family proteases. J. Biol. Chem. 1997, 272, 9677-9682.
25. Lee, D.; Long, S. A.; Adams, J. L.; Chan, G.; Vaidya, K. S.; Francis, T. A.; Kikly, K.; Winkler, J. D.; Sung, C. M.; Debouck, C.; et al. Potent and selective nonpeptide inhibitors of caspases 3 and 7 inhibit apoptosis and maintain cell functionatity. J. Biol. Chem. 2000, 275, 16007-16014.
26. Nuttall, M. E.; Lee, D.; McLaughlin, B.; Erhardt, J. A. Selective inhibitors of apoptotic caspases: implications for novel therapeutic strategies. Drug Discovery Today 2001, 6, 85-91.
27. Lee, D.; Long, S. A.; Murray, J. H.; Adams, J. L.; Nuttall, M. E.; Nadeau, D. P.; Kikly, K.; Winkler, J. D.; Sung, C. M.; Ryan, M. D.; et al. Potent and selective nonpeptide inhibitors of caspases 3 and 7. J. Med. Chem. 2001, 44, 2015-2026.
28. Chu, W.; Zhang, J.; Zeng, C.; Rothfuss, J.; Tu, Z.; Chu, Y.; Reichert, D. E.; Welch, M. J.; Mach, R. H. N -Benzylisatin sulfonamide analogues as potent caspase-3 inhibitors: synthesis, in vitro activity, and molecular modeling studies. J. Med. Chem. 2005, 48, 7637-7647.
29. Kopka, K.; Faust, A.; Keul, P.; Wagner, S.; Breyholz, H. J.; Höltke, C.; Schober, O.; Schafers, M.; Levkau, B. 5-Pyrrolidinylsulfonyl isatin as a potential tool for the molecular imaging of caspases in apoptosis. J. Med. Chem. 2006, 49, 6704-6715.
30. Chu, W.; Rothfuss, J.; D'Avignon, A.; Zeng, C.; Zhou, D.; Hotchkiss, R. S.; Mach, R. H. Isatin sulfonamide analogs containing a Mchael addition acceptor: a new class of caspase 3/7 inhibitors. J. Med. Chem 2007, 50, 3751-3755.
31. Wang, Y.; Mathis, C. A.; Huang, G. F.; Debnath, M. L.; Holt, D. P.; Shao, L.; Klunk, W. E. Effects of lipophilicity on the affinity and nonspecific binding of iodinated benzothiazole derivatives. J. Mol. Neuroscience 2003, 20, 255-260.