Efficient Synthesis of Amine-Linked 2,4,6-Trisubstituted Pyrimidines as a New Class of Bacterial FtsZ Inhibitors

ACS Omega

Volumn 2, Issue 10, 2017, Pages 7281-7292

  Chan, Kin Fai ^a   Sun, Ning ^a   Yan, Siu Cheong ^a   Wong, Iris L K ^a   Lui, Hok Kiu ^a   Cheung, Kwan Choi ^a   Yuan, Jian ^a   Chan, Fung Yi ^a   Zheng, Zhiwei ^a   Chan, Edward W C ^a   Chen, Sheng ^a   Leung, Yun Chung ^a   Chan, Tak Hang ^a,b   Wong, Kwok Yin ^a  

^a HONG KONG POLYTECHNIC UNIVERSITY   (Hong Kong)

^b MCGILL UNIVERSITY   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 85032574341     PISSN: None     EISSN: 24701343     Source Type: Journal    
DOI: 10.1021/acsomega.7b00701     Document Type: Article

References (44)

1. Klevens, R. M.; Morrison, M. A.; Nadle, J. et al. Invasive methicillin-resistant staphylococcus aureus infections in the united states JAMA, J. Am. Med. Assoc. 2007, 298, 1763-1771 10.1001/jama.298.15.1763
2. http://www.cdc.gov/drugresistance/pdf/ar-threats-2013-508.pdf (accessed July 15, 2017).
3. Lock, R. L.; Harry, E. J. Cell-division inhibitors: new insights for future antibiotics Nat. Rev. Drug Discovery 2008, 7, 324-338 10.1038/nrd2510
4. Sass, P.; Brötz-Oesterhelt, H. Bacterial cell division as a target for new antibiotics Curr. Opin. Microbiol. 2013, 16, 522-530 10.1016/j.mib.2013.07.006
5. Foss, M. H.; Eun, Y.-J.; Weibel, D. B. Chemical-Biological Studies of Subcellular Organization in Bacteria Biochemistry 2011, 50, 7719-7734 10.1021/bi200940d
6. Schaffner-Barbero, C.; Martín-Fontecha, M.; Chacón, P.; Andreu, J. M. Targeting the Assembly of Bacterial Cell Division Protein FtsZ with Small Molecules ACS Chem. Biol. 2012, 7, 269-277 10.1021/cb2003626
7. Ma, S.; Ma, S. The Development of FtsZ Inhibitors as Potential Antibacterial Agents ChemMedChem 2012, 7, 1161-1172 10.1002/cmdc.201200156
8. Ojima, I.; Kumar, K.; Awasthi, D.; Vineberg, J. G. Drug discovery targeting cell division proteins, microtubules and FtsZ Bioorg. Med. Chem. 2014, 22, 5060-5077 10.1016/j.bmc.2014.02.036
9. Hurley, K. A.; Santos, T. M. A.; Nepomuceno, G. M.; Huynh, V.; Shaw, J. T.; Weibel, D. B. Targeting the bacterial division protein FtsZ J. Med. Chem. 2016, 59, 6975-6998 10.1021/acs.jmedchem.5b01098
10. Anderson, D. E.; Kim, M. B.; Moore, J. T.; O'Brien, T. E.; Sorto, N. A.; Grove, C. I.; Lackner, L. L.; Ames, J. B.; Shaw, J. T. Comparison of Small Molecule Inhibitors of the Bacterial Cell Division Protein FtsZ and Identification of a Reliable Cross-Species Inhibitor ACS Chem. Biol. 2012, 7, 1918-1928 10.1021/cb300340j
11. Li, Y.; Hsin, J.; Zhao, L.; Cheng, Y.; Shang, W.; Huang, K. C.; Wang, H.-W.; Ye, S. FtsZ Protofilaments Use a Hinge-Opening Mechanism for Constrictive Force Generation Science 2013, 341, 392-395 10.1126/science.1239248
12. Matsui, T.; Han, X.; Yu, J.; Yao, M.; Tanaka, I. Structural Change in FtsZ Induced by Intermolecular Interactions between Bound GTP and the T7 Loop J. Biol. Chem. 2014, 289, 3501-3509 10.1074/jbc.m113.514901
13. Haydon, D. J.; Stokes, N. R.; Ure, R.; Galbraith, G.; Bennett, J. M.; Brown, D. R.; Baker, P. J.; Barynin, V. V.; Rice, D. W.; Sedelnikova, S. E.; Heal, J. R.; Sheridan, J. M.; Aiwale, S. T.; Chauhan, P. K.; Srivastava, A.; Taneja, A.; Collins, I.; Errington, J.; Czaplewski, L. G. An inhibitor of FtsZ with potent and selective anti-staphylococcal activity Science 2008, 321, 1673-1675 10.1126/science.1159961
14. Haydon, D. J.; Bennett, J. M.; Brown, D.; Collins, I.; Galbraith, G.; Lancett, P.; Macdonald, R.; Stokes, N. R.; Chauhan, P. K.; Sutariya, J. K.; Nayal, N.; Srivastava, A.; Beanland, J.; Hall, R.; Henstock, V.; Noula, C.; Rockley, C.; Czaplewski, L. Creating an Antibacterial with in Vivo Efficacy: Synthesis and Characterization of Potent Inhibitors of the Bacterial Cell Division Protein FtsZ with Improved Pharmaceutical Properties J. Med. Chem. 2010, 53, 3927-3936 10.1021/jm9016366
15. Qiang, S.; Wang, C.; Venter, H.; Li, X.; Wang, Y.; Guo, L.; Ma, R.; Ma, S. Synthesis and Biological Evaluation of Novel FtsZ-targeted 3-arylalkoxy-2,6-difluorobenzamides as Potential Antimicrobial Agents Chem. Biol. Drug Des. 2016, 87, 257-264 10.1111/cbdd.12658
16. Kaul, M.; Mark, L.; Zhang, Y.; Parhi, A. K.; LaVoie, E. J.; Pilch, D. S. An FtsZ-Targeting Prodrug with Oral Antistaphylococcal Efficacy In Vivo Antimicrob. Agents Chemother. 2013, 57, 5860-5869 10.1128/aac.01016-13
17. Kaul, M.; Mark, L.; Zhang, Y.; Parhi, A. K.; LaVoie, E. J.; Pilch, D. S. Pharmacokinetics and in vivo antistaphylococcal efficacy of TXY541, a 1-methylpiperidine-4-carboxamide prodrug of PC190723 Biochem. Pharmacol. 2013, 86, 1699-1707 10.1016/j.bcp.2013.10.010
18. Kaul, M.; Mark, L.; Zhang, Y.; Parhi, A. K.; Lyu, Y. L.; Pawlak, J.; Saravolatz, S.; Saravolatz, L. D.; Weinstein, M. P.; LaVoie, E. J.; Pilch, D. S. TXA709, an FtsZ-Targeting Benzamide Prodrug with Improved Pharmacokinetics and Enhanced In Vivo Efficacy against Methicillin-Resistant Staphylococcus aureus Antimicrob. Agents Chemother. 2015, 59, 4845-4855 10.1128/aac.00708-15
19. Lepak, A. J.; Parhi, A.; Madison, M.; Marchillo, K.; VanHecker, J.; Andes, D. R. In Vivo Pharmacodynamic Evaluation of an FtsZ Inhibitor, TXA-709, and Its Active Metabolite, TXA-707, in a Murine Neutropenic Thigh Infection Model Antimicrob. Agents Chemother. 2015, 59, 6568-6574 10.1128/aac.01464-15
20. Stokes, N. R.; Baker, N.; Bennett, J. M.; Berry, J.; Collins, I.; Czaplewski, L. G.; Logan, A.; Macdonald, R.; MacLeod, L.; Peasley, H.; Mitchell, J. P.; Nayal, N.; Yadav, A.; Srivastava, A.; Haydon, D. J. An Improved Small-Molecule Inhibitor of FtsZ with Superior In Vitro Potency, Drug-Like Properties, and In Vivo Efficacy Antimicrob. Agents Chemother. 2013, 57, 317-325 10.1128/aac.01580-12
21. Matsui, T.; Yamane, J.; Mogi, N.; Yamaguchi, H.; Takemoto, H.; Yao, M.; Tanaka, I. Structural reorganization of the bacterial cell-division protein FtsZ from Staphylococcus aureus Acta Crystallogr., Sect. D: Biol. Crystallogr. 2012, 68, 1175-1188 10.1107/s0907444912022640
22. Tan, C. M.; Therien, A. G.; Lu, J.; Lee, S. H.; Caron, A.; Gill, C. J.; Lebeau-Jacob, C.; Benton-Perdomo, L.; Monteiro, J. M.; Pereira, P. M.; Elsen, N. L.; Wu, J.; Deschamps, K.; Petcu, M.; Wong, S.; Daigneault, E.; Kramer, S.; Liang, L.; Maxwell, E.; Claveau, D.; Vaillancourt, J.; Skorey, K.; Tam, J.; Wang, H.; Meredith, T. C.; Sillaots, S.; Wang-Jarantow, L.; Ramtohul, Y.; Langlois, E.; Landry, F.; Reid, J. C.; Parthasarathy, G.; Sharma, S.; Baryshnikova, A.; Lumb, K. J.; Pinho, M. G.; Soisson, S. M.; Roemer, T. Restoring Methicillin-Resistant Staphylococcus aureus Susceptibility to β-Lactam Antibiotics Sci. Transl. Med. 2012, 4, 126ra35 10.1126/scitranslmed.3003592
23. Kaul, M.; Parhi, A. K.; Zhang, Y.; LaVoie, E. J.; Tuske, S.; Arnold, E.; Kerrigan, J. E.; Pilch, D. S. A Bactericidal Guanidinomethyl Biaryl That Alters the Dynamics of Bacterial FtsZ Polymerization J. Med. Chem. 2012, 55, 10160-10176 10.1021/jm3012728
24. Margalit, D. N.; Romberg, L.; Mets, R. B.; Hebert, A. M.; Mitchison, T. J.; Kirschner, M. W.; RayChaudhuri, D. Targeting cell division: Small-molecule inhibitors of FtsZ GTPase perturb cytokinetic ring assembly and induce bacterial lethality Proc. Natl. Acad. Sci. U.S.A. 2004, 101, 11821-11826 10.1073/pnas.0404439101
25. Nepomuceno, G. M.; Chan, K. M.; Huynh, V.; Martin, K. S.; Moore, J. T.; O'Brien, T. E.; Pollo, L. A. E.; Sarabia, F. J.; Tadeus, C.; Yao, Z.; Anderson, D. E.; Ames, J. B.; Shaw, J. T. Synthesis and Evaluation of Quinazolines as Inhibitors of the Bacterial Cell Division Protein FtsZ ACS Med. Chem. Lett. 2015, 6, 308-312 10.1021/ml500497s
26. Plaza, A.; Keffer, J. L.; Bifulco, G.; Lloyd, J. R.; Bewley, C. A. Chrysophaentins A-H, Antibacterial Bisdiarylbutene Macrocycles That Inhibit the Bacterial Cell Division Protein FtsZ J. Am. Chem. Soc. 2010, 132, 9069-9077 10.1021/ja102100h
27. Marcelo, F.; Huecas, S.; Ruiz-ávila, L. B.; Cañada, F. J.; Perona, A.; Poveda, A.; Martín-Santamaría, S.; Morreale, A.; Jiménez-Barbero, J.; Andreu, J. M. Interactions of Bacterial Cell Division Protein FtsZ with C8-Substituted Guanine Nucleotide Inhibitors. A Combined NMR, Biochemical and Molecular Modeling Perspective J. Am. Chem. Soc. 2013, 135, 16418-16428 10.1021/ja405515r
28. Huecas, S.; Marcelo, F.; Perona, A.; Ruiz-ávila, L. B.; Morreale, A.; Cañada, F. J.; Jiménez-Barbero, J.; Andreu, J. M. Beyond a Fluorescent Probe: Inhibition of Cell Division Protein FtsZ by mant-GTP Elucidated by NMR and Biochemical Approaches ACS Chem. Biol. 2015, 10, 2382-2392 10.1021/acschembio.5b00444
29. Sun, N.; Chan, F.-Y.; Lu, Y.-J.; Neves, M. A. C.; Lui, H.-K.; Wang, Y.; Chow, K.-Y.; Chan, K.-F.; Yan, S.-C.; Leung, Y.-C.; Abagyan, R.; Chan, T.-H.; Wong, K.-Y. Rational Design of Berberine-Based FtsZ Inhibitors with Broad-Spectrum Antibacterial Activity PLoS One 2014, 9 e97514 10.1371/journal.pone.0097514
30. Domadia, P. N.; Bhunia, A.; Sivaraman, J.; Swarup, S.; Dasgupta, D. Berberine targets assembly of Escherichia coli cell division protein FtsZ Biochemistry 2008, 47, 3225-3234 10.1021/bi7018546
31. Artola, M.; Ruiz-Avila, L. B.; Vergoñós, A.; Huecas, S.; Araujo-Bazán, L.; Martín-Fontecha, M.; Vázquez-Villa, H.; Turrado, C.; Ramírez-Aportela, E.; Hoegl, A.; Nodwell, M.; Barasoain, I.; Chacón, P.; Sieber, S. A.; Andreu, J. M.; López-Rodríguez, M. L. Effective GTP-Replacing FtsZ Inhibitors and Antibacterial Mechanism of Action ACS Chem. Biol. 2015, 10, 834-843 10.1021/cb500974d
32. Ruiz-Avila, L. B.; Huecas, S.; Artola, M.; Vergoñós, A.; Ramírez-Aportela, E.; Cercenado, E.; Barasoain, I.; Vázquez-Villa, H.; Martín-Fontecha, M.; Chacón, P.; López-Rodrĺguez, M. L.; Andreu, J. M. Synthetic Inhibitors of Bacterial Cell Division Targeting the GTP-Binding Site of FtsZ ACS Chem. Biol. 2013, 8, 2072-2083 10.1021/cb400208z
33. Chan, F.-Y.; Sun, N.; Neves, M. A. C.; Lam, P. C.-H.; Chung, W.-H.; Wong, L.-K.; Chow, H.-Y.; Ma, D.-L.; Chan, P.-H.; Leung, Y.-C.; Chan, T.-H.; Abagyan, R.; Wong, K.-Y. Identification of a New Class of FtsZ Inhibitors by Structure-Based Design and in Vitro Screening J. Chem. Inf. Model. 2013, 53, 2131-2140 10.1021/ci400203f
34. Chan, F.-Y.; Sun, N.; Leung, Y.-C.; Wong, K.-Y. Antimicrobial activity of a quinuclidine-based FtsZ inhibitor and its synergistic potential with β-lactam antibiotics J. Antibiot. 2015, 68, 253-258 10.1038/ja.2014.140
35. O'Shea, R.; Moser, H. E. Physicochemical Properties of Antibacterial Compounds: Implications for Drug Discovery J. Med. Chem. 2008, 51, 2871-2878 10.1021/jm700967e
36. Karpov, A. S.; Müller, T. J. J. Straightforward novel one-pot enaminone and pyrimidine syntheses by coupling-addition-cyclocondensation sequences Synthesis 2003, 2815-2826 10.1055/s-2003-42480
37. Clinical and Laboratory Standards Institute. Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria That Grow Aerobically; Approved Standard, 7 th ed.; CLSI document M07-A7; Clinical and Laboratory Standards Institute: Wayne, PA, 2006.
38. Sorto, N. A.; Olmstead, M. M.; Shaw, J. T. Practical Synthesis of PC190723, an Inhibitor of the Bacterial Cell Division Protein FtsZ J. Org. Chem. 2010, 75, 7946-7949 10.1021/jo101720y
39. Tsai, C. J.-Y.; Loh, J. M. S.; Proft, T. Galleria mellonella infection models for the study of bacterial diseases and for antimicrobial drug testing Virulence 2016, 7, 214-229 10.1080/21505594.2015.1135289
40. Mayer, M.; Meyer, B. Characterization of Ligand Binding by Saturation Transfer Difference NMR Spectroscopy Angew. Chem., Int. Ed. 1999, 38, 1784-1788 10.1002/(sici)1521-3773(19990614)38:12<1784::aid-anie1784>3.3.co;2-h
41. Lam, T.; Hilgers, M. T.; Cunningham, M. L.; Kwan, B. P.; Nelson, K. J.; Brown-Driver, V.; Ong, V.; Trzoss, M.; Hough, G.; Shaw, K. J.; Finn, J. Structure-Based Design of New Dihydrofolate Reductase Antibacterial Agents: 7-(Benzimidazol-1-yl)-2,4-diaminoquinazolines J. Med. Chem. 2014, 57, 651-668 10.1021/jm401204g
42. Wang, Y.; Chan, F.-Y.; Sun, N.; Lui, H.-K.; So, P.-K.; Yan, S.-C.; Chan, K.-F.; Chiou, J.; Chen, S.; Abagyan, R.; Leung, Y.-C.; Wong, K.-Y. Structure-based design, synthesis, and biological evaluation of isatin derivatives as potential glycosyltransferase inhibitors Chem. Biol. Drug Des. 2014, 84, 685-696 10.1111/cbdd.12361
43. Horn, K. S. V.; Burda, W. N.; Fleeman, R.; Shaw, L. N.; Manetsch, R. Antibacterial Activity of a Series of N2,N4-Disubstituted Quinazoline-2,4-diamines J. Med. Chem. 2014, 57, 3075-3093 10.1021/jm500039e
44. Lui, H. K. Alkoxy- and amino-benzamides as inhibitors of the bacterial cell division protein FtsZ and antibacterial agents. M. Phil. Thesis, The Hong Kong Polytechnic University, Hong Kong, 2014.