Newly Designed Quinolinol Inhibitors Mitigate the Effects of Botulinum Neurotoxin A in Enzymatic, Cell-Based, and ex Vivo Assays

Journal of Medicinal Chemistry

Volumn 60, Issue 1, 2017, Pages 338-348

  Bremer, Paul T ^a   Adler, Michael ^b   Phung, Cecilia H ^b   Singh, Ajay K ^b   Janda, Kim D ^a  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b US ARMY MEDICAL RESEARCH INSTITUTE OF CHEMICAL DEFENSE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

2 AMINO 5 [(4 CHLOROINDOLIN 1 YL)SULFONYL]QUINOLIN 8 OL; 2 CHLORO 5 [(4 CHLOROINDOLIN 1 YL)SULFONYL]QUINOLIN 8 OL; 5 (PIPERIDIN 1 YLSULFONYL)QUINOLIN 8 OL; 5 [(4 CHLOROINDOLIN 1 YL)SULFONYL] 2 (2 METHYLHYDRAZINYL)QUINOLIN 8 OL; 5 [(4 CHLOROINDOLIN 1 YL)SULFONYL] 2 (ETHYLAMINO)QUINOLIN 8 OL; 5 [(4 CHLOROINDOLIN 1 YL)SULFONYL] 2 (METHYLAMINO)QUINOLIN 8 OL; 5 [(4 CHLOROINDOLIN 1 YL)SULFONYL] 2 HYDRAZINYLQUINOLIN 8 OL; 5 [(4 CHLOROINDOLIN 1 YL)SULFONYL]QUINOLIN 8 OL; 5 [(6 CHLOROINDOLIN 1 YL)SULFONYL]QUINOLIN 8 OL; 8 HYDROXY N METHYL N PHENYLQUINOLINE 5 SULFONAMIDE; 8 HYDROXY N PHENYLQUINOLINE 5 SULFONAMIDE; BOTULINUM TOXIN A; N (3 CHLOROPHENYL) 8 HYDROXY N METHYLQUINOLINE 5 SULFONAMIDE; N (3 CHLOROPHENYL) 8 HYDROXYQUINOLINE 5 SULFONAMIDE; N' [5 [(4 CHLOROINDOLIN 1 YL)SULFONYL] 8 HYDROXYQUINOLIN 2 YL] ACETOHYDRAZIDE; QUINOLINOL DERIVATIVE; UNCLASSIFIED DRUG;

ARTICLE; DRUG DESIGN; ENZYMATIC ASSAY; ENZYME INHIBITION; EX VIVO STUDY; MOLECULAR DOCKING; MOLECULAR LIBRARY; PROTEIN DEGRADATION; STRUCTURE ACTIVITY RELATION; ANIMAL; ANTAGONISTS AND INHIBITORS; CELL CULTURE; CHEMISTRY; MALE; METABOLISM; MOUSE; VALIDATION STUDY;

ANIMALS; BOTULINUM TOXINS, TYPE A; CELLS, CULTURED; HYDROXYQUINOLINES; MALE; MICE; MOLECULAR DOCKING SIMULATION; PROTEOLYSIS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 85018193326     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.6b01393     Document Type: Article

References (52)

1. Sugiyama, H. Clostridium botulinum neurotoxin Microbiol. Rev. 1980, 44, 419-448
2. Arnon, S. S.; Schechter, R.; Inglesby, T. V.; Henderson, D. A.; Bartlett, J. G.; Ascher, M. S.; Eitzen, E.; Fine, A. D.; Hauer, J.; Layton, M.; Lillibridge, S.; Osterholm, M. T.; O’Toole, T.; Parker, G.; Perl, T. M.; Russell, P. K.; Swerdlow, D. L.; Tonat, K. Botulinum toxin as a biological weapon: Medical and public health management J. Am. Med. Assoc. 2001, 285, 1059-1070 10.1001/jama.285.8.1059
3. Schantz, E. J.; Johnson, E. A. Properties and use of botulinum toxin and other microbial neurotoxins in medicine Microbiol. Rev. 1992, 56, 80-99
4. Jankovic, J. Botulinum toxin in clinical practice J. Neurol., Neurosurg. Psychiatry 2004, 75, 951-957 10.1136/jnnp.2003.034702
5. Fagien, S. Botox for the treatment of dynamic and hyperkinetic facial lines and furrows: Adjunctive use in facial aesthetic surgery Plast. Reconstr. Surg. 1999, 103, 701-713 10.1097/00006534-199902000-00055
6. Frampton, J. E. Onabotulinumtoxin A (BOTOX ®): A review of its use in the prophylaxis of headaches in adults with chronic migraine Drugs 2012, 72, 825-845 10.2165/11208880-000000000-00000
7. Odergren, T.; Hjaltason, H.; Kaakkola, S.; Solders, G.; Hanko, J.; Fehling, C.; Marttila, R. J.; Lundh, H.; Gedin, S.; Westergren, I.; Richardson, A.; Dott, C.; Cohen, H. A double blind, randomised, parallel group study to investigate the dose equivalence of Dysport (R) and Botox (R) in the treatment of cervical dystonia J. Neurol., Neurosurg. Psychiatry 1998, 64, 6-12 10.1136/jnnp.64.1.6
8. Truong, D. D.; Rontal, M.; Rolnick, M.; Aronson, A. E.; Mistura, K. Double-blind controlled study of botulinum toxin in adductor spasmodic dysphonia Laryngoscope 1991, 101, 630-634 10.1288/00005537-199106000-00010
9. Roggenkamper, P.; Jost, W. H.; Bihari, K.; Comes, G.; Grafe, S.; NT 201 Blepharospasm Study Team. Efficacy and safety of a new botulinum toxin type A free of complexing proteins in the treatment of blepharospasm J. Neural Transm. 2006, 113, 303-312 10.1007/s00702-005-0323-3
10. Woodruff, B. A.; Griffin, P. M.; Mccroskey, L. M.; Smart, J. F.; Wainwright, R. B.; Bryant, R. G.; Hutwagner, L. C.; Hatheway, C. L. Clinical and laboratory comparison of botulism from toxin type-A, type-B, and type-E in the United States, 1975-1988 J. Infect. Dis. 1992, 166, 1281-1286 10.1093/infdis/166.6.1281
11. McCarty, C. L.; Angelo, K.; Beer, K. D.; Cibulskas-White, K.; Quinn, K.; de Fijter, S.; Bokanyi, R.; St. Germain, E.; Baransi, K.; Barlow, K.; Shafer, G.; Hanna, L.; Spindler, K.; Walz, E.; DiOrio, M.; Jackson, B. R.; Luquez, C.; Mahon, B. E.; Basler, C.; Curran, K.; Matanock, A.; Walsh, K.; Slifka, K. J.; Rao, A. K. Large outbreak of botulism associated with a church potluck meal-Ohio, 2015 MMWR Morb. Mortal. Wkly. Rep. 2015, 64, 802-803 10.15585/mmwr.mm6429a6
12. Wein, L. M.; Liu, Y. F. Analyzing a bioterror attack on the food supply: The case of botulinum toxin in milk Proc. Natl. Acad. Sci. U. S. A. 2005, 102, 9984-9989 10.1073/pnas.0408526102
13. Henderson, D. A. The looming threat of bioterrorism Science 1999, 283, 1279-1282 10.1126/science.283.5406.1279
14. Tacket, C. O.; Shandera, W. X.; Mann, J. M.; Hargrett, N. T.; Blake, P. A. Equine antitoxin use and other factors that predict outcome in type-A foodborne botulism Am. J. Med. 1984, 76, 794-798 10.1016/0002-9343(84)90988-4
15. Simpson, L. I. The binary toxin produced by Clostridium botulinum enters cells by receptor-mediated endocytosis to exert its pharmacologic effects J. Pharmacol. Exp. Ther. 1989, 251, 1223-1228
16. Blasi, J.; Chapman, E. R.; Link, E.; Binz, T.; Yamasaki, S.; De Camilli, P.; Sudhof, T. C.; Niemann, H.; Jahn, R. Botulinum neurotoxin A selectively cleaves the synaptic protein SNAP-25 Nature 1993, 365, 160-163 10.1038/365160a0
17. Schiavo, G.; Rossetto, O.; Tonello, F.; Montecucco, C. Intracellular targets and metalloprotease activity of tetanus and botulism neurotoxins Curr. Top. Microbiol. Immunol. 1995, 195, 257-274 10.1007/978-3-642-85173-5_12
18. Seki, H.; Xue, S.; Pellett, S.; Šilhár, P.; Johnson, E. A.; Janda, K. D. Cellular protection of SNAP-25 against botulinum neurotoxin/A: Inhibition of thioredoxin reductase through a suicide substrate mechanism J. Am. Chem. Soc. 2016, 138, 5568-5575 10.1021/jacs.5b12929
19. Sheridan, R. E.; Deshpande, S. S.; Nicholson, J. D.; Adler, M. Structural features of aminoquinolines necessary for antagonist activity against botulinum neurotoxin Toxicon 1997, 35, 1439-1451 10.1016/S0041-0101(96)00208-5
20. Deshpande, S. S.; Sheridan, R. E.; Adler, M. Efficacy of certain quinolines as pharmacological antagonists in botulinum neurotoxin poisoning Toxicon 1997, 35, 433-445 10.1016/S0041-0101(96)00147-X
21. Kiris, E.; Nuss, J. E.; Stanford, S. M.; Wanner, L. M.; Cazares, L.; Maestre, M. F.; Du, H. T.; Gomba, G. Y.; Burnett, J. C.; Gussio, R.; Bottini, N.; Panchal, R. G.; Kane, C. D.; Tessarollo, L.; Bavari, S. Phosphatase inhibitors function as novel, broad spectrum botulinum neurotoxin antagonists in mouse and human embryonic stem cell-derived motor neuron-based assays PLoS One 2015, 10, e0129264 10.1371/journal.pone.0129264
22. Kiris, E.; Burnett, J. C.; Nuss, J. E.; Wanner, L. M.; Peyser, B. D.; Du, H. T.; Gomba, G. Y.; Kota, K. P.; Panchal, R. G.; Gussio, R.; Kane, C. D.; Tessarollo, L.; Bavari, S. Src family kinase inhibitors antagonize the toxicity of multiple serotypes of botulinum neurotoxin in human embryonic stem cell-derived motor neurons Neurotoxic. Res. 2015, 27, 384-398 10.1007/s12640-015-9526-z
23. Boldt, G. E.; Kennedy, J. P.; Janda, K. D. Identification of a potent botulinum neurotoxin a protease inhibitor using in situ lead identification chemistry Org. Lett. 2006, 8, 1729-1732 10.1021/ol0603211
24. Silvaggi, N. R.; Boldt, G. E.; Hixon, M. S.; Kennedy, J. P.; Tzipori, S.; Janda, K. D.; Allen, K. N. Structures of Clostridium botulinum neurotoxin serotype A light chain complexed with small-molecule inhibitors highlight active-site flexibility Chem. Biol. 2007, 14, 533-542 10.1016/j.chembiol.2007.03.014
25. Silhar, P.; Silvaggi, N. R.; Pellett, S.; Capkova, K.; Johnson, E. A.; Allen, K. N.; Janda, K. D. Evaluation of adamantane hydroxamates as botulinum neurotoxin inhibitors: Synthesis, crystallography, modeling, kinetic and cellular based studies Bioorg. Med. Chem. 2013, 21, 1344-1348 10.1016/j.bmc.2012.12.001
26. Kumaran, D.; Rawat, R.; Ludivico, M. L.; Ahmed, S. A.; Swaminathan, S. Structure-and substrate-based inhibitor design for Clostridium botulinum neurotoxin serotype A J. Biol. Chem. 2008, 283, 18883-18891 10.1074/jbc.M801240200
27. Silhar, P.; Capkova, K.; Salzameda, N. T.; Barbieri, J. T.; Hixon, M. S.; Janda, K. D. Botulinum neurotoxin A protease: Discovery of natural product exosite inhibitors J. Am. Chem. Soc. 2010, 132, 2868 10.1021/ja910761y
28. Caglic, D.; Krutein, M. C.; Bompiani, K. M.; Barlow, D. J.; Benoni, G.; Pelletier, J. C.; Reitz, A. B.; Lairson, L. L.; Houseknecht, K. L.; Smith, G. R.; Dickerson, T. J. Identification of clinically viable quinolinol inhibitors of botulinum neurotoxin A light chain J. Med. Chem. 2014, 57, 669-676 10.1021/jm4012164
29. Roxas-Duncan, V.; Enyedy, I.; Montgomery, V. A.; Eccard, V. S.; Carrington, M. A.; Lai, H. G.; Gul, N.; Yang, D. C. H.; Smith, L. A. Identification and biochemical characterization of small-molecule inhibitors of Clostridium botulinum neurotoxin serotype A Antimicrob. Agents Chemother. 2009, 53, 3478-3486 10.1128/AAC.00141-09
30. Lai, H. G.; Feng, M. H.; Roxas-Duncan, V.; Dakshanamurthy, S.; Smith, L. A.; Yang, D. C. H. Quinolinol and peptide inhibitors of zinc protease in botulinum neurotoxin A: Effects of zinc ion and peptides on inhibition Arch. Biochem. Biophys. 2009, 491, 75-84 10.1016/j.abb.2009.09.008
31. Videnovic, M.; Opsenica, D. M.; Burnett, J. C.; Gomba, L.; Nuss, J. E.; Selakovic, Z.; Konstantinovic, J.; Krstic, M.; Segan, S.; Zlatovic, M.; Sciotti, R. J.; Bavari, S.; Solaja, B. A. Second generation steroidal 4-aminoquinolines are potent, dual-target inhibitors of the botulinum neurotoxin serotype A metalloprotease and P. falciparum malaria J. Med. Chem. 2014, 57, 4134-4153 10.1021/jm500033r
32. Jacobsen, F. E.; Lewis, J. A.; Cohen, S. M. A new role for old ligands: Discerning chelators for zinc metalloproteinases J. Am. Chem. Soc. 2006, 128, 3156-3157 10.1021/ja057957s
33. Puerta, D. T.; Lewis, J. A.; Cohen, S. M. New beginnings for matrix metalloproteinase inhibitors: Identification of high-affinity zinc-binding groups J. Am. Chem. Soc. 2004, 126, 8388-8389 10.1021/ja0485513
34. Jacobsen, J. A.; Fullagar, J. L.; Miller, M. T.; Cohen, S. M. Identifying chelators for metalloprotein inhibitors using a fragment-based approach J. Med. Chem. 2011, 54, 591-602 10.1021/jm101266s
35. Zuniga, J. E.; Schmidt, J. J.; Fenn, T.; Burnett, J. C.; Arac, D.; Gussio, R.; Stafford, R. G.; Badie, S. S.; Bavari, S.; Brunger, A. T. A potent peptidomimetic inhibitor of botulinum neurotoxin serotype A has a very different conformation than SNAP-25 substrate Structure 2008, 16, 1588-1597 10.1016/j.str.2008.07.011
36. Silhar, P.; Lardy, M. A.; Hixon, M. S.; Shoemaker, C. B.; Barbieri, J. T.; Struss, A. K.; Lively, J. M.; Javor, S.; Janda, K. D. C-terminus of botulinum A protease has profound and unanticipated kinetic consequences upon the catalytic cleft ACS Med. Chem. Lett. 2013, 4, 283-287 10.1021/ml300428s
37. Rubbo, S. D.; Albert, A.; Gibson, M. I. The influence of chemical constitution on antibacterial activity. Part 5: The antibacterial action of 8-hydroxyquinoline (oxine) Br. J. Exp. Pathol. 1950, 31, 425-441
38. Cherny, R. A.; Atwood, C. S.; Xilinas, M. E.; Gray, D. N.; Jones, W. D.; McLean, C. A.; Barnham, K. J.; Volitakis, I.; Fraser, F. W.; Kim, Y. S.; Huang, X. D.; Goldstein, L. E.; Moir, R. D.; Lim, J. T.; Beyreuther, K.; Zheng, H.; Tanzi, R. E.; Masters, C. L.; Bush, A. I. Treatment with a copper-zinc chelator markedly and rapidly inhibits beta-amyloid accumulation in Alzheimer’s disease transgenic mice Neuron 2001, 30, 665-676 10.1016/S0896-6273(01)00317-8
39. OMEGA, version 2.4.6; OpenEye Scientific Software: Santa Fe, NM; http://www.eyesopen.com.
40. Hawkins, P. C. D.; Nicholls, A. Conformer Generation with OMEGA: Learning from the data set and the analysis of failures J. Chem. Inf. Model. 2012, 52, 2919-2936 10.1021/ci300314k
41. Hawkins, P. C. D.; Skillman, A. G.; Warren, G. L.; Ellingson, B. A.; Stahl, M. T. Conformer generation with OMEGA: Algorithm and validation using high quality structures from the Protein Databank and Cambridge Structural Database J. Chem. Inf. Model. 2010, 50, 572-584 10.1021/ci100031x
42. FRED, version 2.2.5; OpenEye Scientific Software: Santa Fe, NM; http://www.eyesopen.com.
43. McGann, M. FRED pose prediction and virtual screening accuracy J. Chem. Inf. Model. 2011, 51, 578-596 10.1021/ci100436p
44. McGann, M. FRED and HYBRID docking performance on standardized datasets J. Comput.-Aided Mol. Des. 2012, 26, 897-906 10.1007/s10822-012-9584-8
45. Chardin, P.; McCormick, F. Brefeldin A: The advantage of being uncompetitive Cell 1999, 97, 153-155 10.1016/S0092-8674(00)80724-2
46. Lin, C. W.; Sie, H. G.; Fishman, W. H. L-tryptophan. A non-allosteric organ-specific uncompetitive inhibitor of human placental alkaline phosphatase Biochem. J. 1971, 124, 509-516 10.1042/bj1240509
47. Dong, M.; Tepp, W. H.; Johnson, E. A.; Chapman, E. R. Using fluorescent sensors to detect botulinum neurotoxin activity in vitro and in living cells Proc. Natl. Acad. Sci. U. S. A. 2004, 101, 14701-14706 10.1073/pnas.0404107101
48. Adler, M.; Dinterman, R. E.; Wannemacher, R. W. Protection by the heavy metal chelator N,N,N′,N′-tetrakis (2-pyridylmethyl)ethylenediamine (TPEN) against the lethal action of botulinum neurotoxin A and B Toxicon 1997, 35, 1089-1100 10.1016/S0041-0101(96)00215-2
49. Make Receptor, version 3.0.1; OpenEye Scientific Software: Santa Fe, NM; http://www.eyesopen.com.
50. VIDA, version 4.3.0.4; OpenEye Scientific Software: Santa Fe, NM; http://www.eyesopen.com.
51. Pearce, D. A.; Jotterand, N.; Carrico, I. S.; Imperiali, B. Derivatives of 8-hydroxy-2-methylquinoline are powerful prototypes for zinc sensors in biological systems J. Am. Chem. Soc. 2001, 123, 5160-5161 10.1021/ja0039839
52. Ariyasu, S.; Sawa, A.; Morita, A.; Hanaya, K.; Hoshi, M.; Takahashi, I.; Wang, B.; Aoki, S. Design and synthesis of 8-hydroxyquinoline-based radioprotective agents Bioorg. Med. Chem. 2014, 22, 3891-3905 10.1016/j.bmc.2014.06.017