Discovery of a novel and potent class of F. tularensis enoyl-reductase (FabI) inhibitors by molecular shape and electrostatic matching

Journal of Medicinal Chemistry

Volumn 55, Issue 1, 2012, Pages 268-279

  Hevener, Kirk E ^a   Mehboob, Shahila ^a   Su, Pin Chih ^a   Truong, Kent ^a   Boci, Teuta ^a   Deng, Jiangping ^b   Ghassemi, Mahmood ^b   Cook, James L ^b   Johnson, Michael E ^a  

^a UNIVERSITY OF ILLINOIS AT CHICAGO   (United States)

^b UNIVERSITY OF ILLINOIS   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTIINFECTIVE AGENT; CIPROFLOXACIN; IMIDAZOLE; OXIDOREDUCTASE; OXIDOREDUCTASE INHIBITOR; PROTEIN FABI; UNCLASSIFIED DRUG;

ANTIBACTERIAL ACTIVITY; ARTICLE; CONTROLLED STUDY; DRUG IDENTIFICATION; DRUG SCREENING; ENZYME INHIBITION; FRANCISELLA TULARENSIS; HIGH THROUGHPUT SCREENING; IC 50; MINIMUM INHIBITORY CONCENTRATION; STATIC ELECTRICITY; STRUCTURE ACTIVITY RELATION; VALIDATION STUDY;

ANTI-BACTERIAL AGENTS; BENZIMIDAZOLES; BENZYL COMPOUNDS; DATABASES, FACTUAL; ENOYL-(ACYL-CARRIER PROTEIN) REDUCTASE (NADPH, B-SPECIFIC); FRANCISELLA TULARENSIS; GRAM-NEGATIVE BACTERIA; GRAM-POSITIVE BACTERIA; MICROBIAL SENSITIVITY TESTS; MODELS, MOLECULAR; MOLECULAR CONFORMATION; STATIC ELECTRICITY; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84863393574     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm201168g     Document Type: Article

References (56)

1. Zhang, Y. M.; White, S. W.; Rock, C. O. Inhibiting bacterial fatty acid synthesis J. Biol. Chem. 2006, 281, 17541-17544
2. Wright, H. T.; Reynolds, K. A. Antibacterial targets in fatty acid biosynthesis Curr. Opin. Microbiol. 2007, 10, 447-453
3. Bergler, H.; Fuchsbichler, S.; Hogenauer, G.; Turnowsky, F. The enoyl-[acyl-carrier-protein] reductase (FabI) of Escherichia coli, which catalyzes a key regulatory step in fatty acid biosynthesis, accepts NADH and NADPH as cofactors and is inhibited by palmitoyl-CoA Eur. J. Biochem. 1996, 242, 689-694
4. Heath, R. J.; Rock, C. O. A triclosan-resistant bacterial enzyme Nature 2000, 406, 145-146
5. Heath, R. J.; Su, N.; Murphy, C. K.; Rock, C. O. The enoyl-[acyl-carrier- protein] reductases FabI and FabL from Bacillus subtilis J. Biol. Chem. 2000, 275, 40128-40133
6. Massengo-Tiasse, R. P.; Cronan, J. E. Vibrio cholerae FabV defines a new class of enoyl-acyl carrier protein reductase J. Biol. Chem. 2008, 283, 1308-1316
7. Zhu, L.; Lin, J.; Ma, J.; Cronan, J. E.; Wang, H. Triclosan resistance of Pseudomonas aeruginosa PAO1 is due to FabV, a triclosan-resistant enoyl-acyl carrier protein reductase Antimicrob. Agents Chemother. 2010, 54, 689-698
8. Wen, L.; Chmielowski, J. N.; Bohn, K. C.; Huang, J. K.; Timsina, Y. N.; Kodali, P.; Pathak, A. K. Functional expression of Francisella tularensis FabH and FabI, potential antibacterial targets Protein Expr. Purif. 2009, 65, 83-91
9. Pohanka, M.; Skladal, P. Bacillus anthracis, Francisella tularensis and Yersinia pestis. The most important bacterial warfare agents-review Folia Microbiol. (Prague, Czech Repub.) 2009, 54, 263-272
10. Oyston, P. C.; Sjostedt, A.; Titball, R. W. Tularaemia: bioterrorism defence renews interest in Francisella tularensis Nature Rev. Microbiol. 2004, 2, 967-978
11. Hepburn, M. J.; Simpson, A. J. Tularemia: current diagnosis and treatment options Expert Rev. Anti-Infect. Ther. 2008, 6, 231-240
12. Lu, H.; England, K.; am Ende, C.; Truglio, J. J.; Luckner, S.; Reddy, B. G.; Marlenee, N. L.; Knudson, S. E.; Knudson, D. L.; Bowen, R. A.; Kisker, C.; Slayden, R. A.; Tonge, P. J. Slow-onset inhibition of the FabI enoyl reductase from Francisella tularensis: residence time and in vivo activity ACS Chem. Biol. 2009, 4, 221-231
13. England, K.; am Ende, C.; Lu, H.; Sullivan, T. J.; Marlenee, N. L.; Bowen, R. A.; Knudson, S. E.; Knudson, D. L.; Tonge, P. J.; Slayden, R. A. Substituted diphenyl ethers as a broad-spectrum platform for the development of chemotherapeutics for the treatment of tularaemia J. Antimicrob. Chemother. 2009, 64, 1052-1061
14. Brinster, S.; Lamberet, G.; Staels, B.; Trieu-Cuot, P.; Gruss, A.; Poyart, C. Type II fatty acid synthesis is not a suitable antibiotic target for Gram-positive pathogens Nature 2009, 458, 83-86
15. Balemans, W.; Lounis, N.; Gilissen, R.; Guillemont, J.; Simmen, K.; Andries, K.; Koul, A. Essentiality of FASII pathway for Staphylococcus aureus. Nature 2010, 463, E3; discussion E4.
16. Miller, W. H.; Seefeld, M. A.; Newlander, K. A.; Uzinskas, I. N.; Burgess, W. J.; Heerding, D. A.; Yuan, C. C.; Head, M. S.; Payne, D. J.; Rittenhouse, S. F.; Moore, T. D.; Pearson, S. C.; Berry, V.; DeWolf, W. E., Jr.; Keller, P. M.; Polizzi, B. J.; Qiu, X.; Janson, C. A.; Huffman, W. F. Discovery of aminopyridine-based inhibitors of bacterial enoyl-ACP reductase (FabI) J. Med. Chem. 2002, 45, 3246-3256
17. Seefeld, M. A.; Miller, W. H.; Newlander, K. A.; Burgess, W. J.; DeWolf, W. E., Jr.; Elkins, P. A.; Head, M. S.; Jakas, D. R.; Janson, C. A.; Keller, P. M.; Manley, P. J.; Moore, T. D.; Payne, D. J.; Pearson, S.; Polizzi, B. J.; Qiu, X.; Rittenhouse, S. F.; Uzinskas, I. N.; Wallis, N. G.; Huffman, W. F. Indole naphthyridinones as inhibitors of bacterial enoyl-ACP reductases FabI and FabK J. Med. Chem. 2003, 46, 1627-1635
18. White, S. W.; Zheng, J.; Zhang, Y. M. Rock. The structural biology of type II fatty acid biosynthesis Annu. Rev. Biochem. 2005, 74, 791-831
19. Mehboob, S.; Truong, K.; Santarsiero, B. D.; Johnson, M. E. Structure of the Francisella tularensis enoyl-acyl carrier protein reductase (FabI) in complex with NAD(+) and triclosan Acta Crystallogr., Sect. F: Struct. Biol. Cryst. Commun. 2010, 66, 1436-1440
20. Priyadarshi, A.; Kim, E. E.; Hwang, K. Y. Structural insights into Staphylococcus aureus enoyl-ACP reductase (FabI), in complex with NADP and triclosan Proteins: Struct., Funct., Bioinf. 2010, 78, 480-486
21. Rafi, S.; Novichenok, P.; Kolappan, S.; Zhang, X.; Stratton, C. F.; Rawat, R.; Kisker, C.; Simmerling, C.; Tonge, P. J. Structure of acyl carrier protein bound to FabI, the FASII enoyl reductase from Escherichia coli J. Biol. Chem. 2006, 281, 39285-39293
22. Pettersen, E. F.; Goddard, T. D.; Huang, C. C.; Couch, G. S.; Greenblatt, D. M.; Meng, E. C.; Ferrin, T. E. UCSF Chimera-a visualization system for exploratory research and analysis J. Comput. Chem. 2004, 25, 1605-1612
23. Lu, H.; Tonge, P. J. Inhibitors of FabI, an enzyme drug target in the bacterial fatty acid biosynthesis pathway Acc. Chem. Res. 2008, 41, 11-20
24. Xu, H.; Sullivan, T. J.; Sekiguchi, J.; Kirikae, T.; Ojima, I.; Stratton, C. F.; Mao, W.; Rock, F. L.; Alley, M. R.; Johnson, F.; Walker, S. G.; Tonge, P. J. Mechanism and inhibition of saFabI, the enoyl reductase from Staphylococcus aureus Biochemistry 2008, 47, 4228-4236
25. Stewart, M. J.; Parikh, S.; Xiao, G.; Tonge, P. J.; Kisker, C. Structural basis and mechanism of enoyl reductase inhibition by triclosan J. Mol. Biol. 1999, 290, 859-865
26. Priyadarshi, A.; Kim, E. E.; Hwang, K. Y. Structural insights into Staphylococcus aureus enoyl-ACP reductase (FabI), in complex with NADP and triclosan. Proteins: Struct., Funct., Bioinf. 2009.
27. Seefeld, M. A.; Miller, W. H.; Newlander, K. A.; Burgess, W. J.; Payne, D. J.; Rittenhouse, S. F.; Moore, T. D.; DeWolf, W. E., Jr.; Keller, P. M.; Qiu, X.; Janson, C. A.; Vaidya, K.; Fosberry, A. P.; Smyth, M. G.; Jaworski, D. D.; Slater-Radosti, C.; Huffman, W. F. Inhibitors of bacterial enoyl acyl carrier protein reductase (FabI): 2,9-disubstituted 1,2,3,4-tetrahydropyrido[3,4- b ]indoles as potential antibacterial agents Bioorg. Med. Chem. Lett. 2001, 11, 2241-2244
28. Heerding, D. A.; Chan, G.; DeWolf, W. E.; Fosberry, A. P.; Janson, C. A.; Jaworski, D. D.; McManus, E.; Miller, W. H.; Moore, T. D.; Payne, D. J.; Qiu, X.; Rittenhouse, S. F.; Slater-Radosti, C.; Smith, W.; Takata, D. T.; Vaidya, K. S.; Yuan, C. C.; Huffman, W. F. 1,4-Disubstituted imidazoles are potential antibacterial agents functioning as inhibitors of enoyl acyl carrier protein reductase (FabI) Bioorg. Med. Chem. Lett. 2001, 11, 2061-2065
29. Kuo, M. R.; Morbidoni, H. R.; Alland, D.; Sneddon, S. F.; Gourlie, B. B.; Staveski, M. M.; Leonard, M.; Gregory, J. S.; Janjigian, A. D.; Yee, C.; Musser, J. M.; Kreiswirth, B.; Iwamoto, H.; Perozzo, R.; Jacobs, W. R., Jr.; Sacchettini, J. C.; Fidock, D. A. Targeting tuberculosis and malaria through inhibition of enoyl reductase: compound activity and structural data J. Biol. Chem. 2003, 278, 20851-20859
30. Payne, D. J.; Miller, W. H.; Berry, V.; Brosky, J.; Burgess, W. J.; Chen, E.; DeWolf, W. E., Jr.; Fosberry, A. P.; Greenwood, R.; Head, M. S.; Heerding, D. A.; Janson, C. A.; Jaworski, D. D.; Keller, P. M.; Manley, P. J.; Moore, T. D.; Newlander, K. A.; Pearson, S.; Polizzi, B. J.; Qiu, X.; Rittenhouse, S. F.; Slater-Radosti, C.; Salyers, K. L.; Seefeld, M. A.; Smyth, M. G.; Takata, D. T.; Uzinskas, I. N.; Vaidya, K.; Wallis, N. G.; Winram, S. B.; Yuan, C. C.; Huffman, W. F. Discovery of a novel and potent class of FabI-directed antibacterial agents Antimicrob. Agents Chemother. 2002, 46, 3118-3124
31. Morde, V. A.; Shaikh, M. S.; Pissurlenkar, R. R.; Coutinho, E. C. Molecular modeling studies, synthesis, and biological evaluation of Plasmodium falciparum enoyl-acyl carrier protein reductase (PfENR) inhibitors Mol. Divers. 2009, 13, 501-517
32. Irwin, J. J. Community benchmarks for virtual screening J. Comput.-Aided Mol. Des. 2008, 22, 193-199
33. ROCS, version 3.1.1; OpenEye Scientific Software, Inc.: Santa Fe, NM, 2010; www.eyesopen.com.
34. EON, version 2.0.1; OpenEye Scientific Software, Inc.: Santa Fe, NM, 2010; www.eyesopen.com.
35. Muchmore, S. W.; Souers, A. J.; Akritopoulou-Zanze, I. The use of three-dimensional shape and electrostatic similarity searching in the identification of a melanin-concentrating hormone receptor 1 antagonist Chem. Biol. Drug Des. 2006, 67, 174-176
36. Naylor, E.; Arredouani, A.; Vasudevan, S. R.; Lewis, A. M.; Parkesh, R.; Mizote, A.; Rosen, D.; Thomas, J. M.; Izumi, M.; Ganesan, A.; Galione, A.; Churchill, G. C. Identification of a chemical probe for NAADP by virtual screening Nature Chem. Biol. 2009, 5, 220-226
37. Lopez-Ramos, M.; Perruccio, F. HPPD: ligand- and target-based virtual screening on a herbicide target J. Chem. Inf. Model. 2010, 50, 801-814
38. Hawkins, P. C.; Skillman, A. G.; Nicholls, A. Comparison of shape-matching and docking as virtual screening tools J. Med. Chem. 2007, 50, 74-82
39. Liu, T.; Lin, Y.; Wen, X.; Jorissen, R. N.; Gilson, M. K. BindingDB: a web-accessible database of experimentally determined protein-ligand binding affinities Nucleic Acids Res. 2007, 35, D198-D201
40. Walter, R. D.; Konigk, E. 7,8-Dihydropteroate-synthesizing enzyme from Plasmodium chabaudi Methods Enzymol. 1980, 66, 564-570
41. Sherman, W.; Day, T.; Jacobson, M. P.; Friesner, R. A.; Farid, R. Novel procedure for modeling ligand/receptor induced fit effects J. Med. Chem. 2006, 49, 534-553
42. Wang, J.; Wolf, R. M.; Caldwell, J. W.; Kollman, P. A.; Case, D. A. Development and testing of a general amber force field J. Comput. Chem. 2004, 25, 1157-1174
43. Triballeau, N.; Acher, F.; Brabet, I.; Pin, J. P.; Bertrand, H. O. Virtual screening workflow development guided by the "receiver operating characteristic" curve approach. Application to high-throughput docking on metabotropic glutamate receptor subtype 4 J. Med. Chem. 2005, 48, 2534-2547
44. Pearlman, R. S. Rapid Generation of High Quality Approximate 3-Dimension Molecular Structures Chem. Des. Autom. News 1987, 2, 1-7
45. Sastry, M.; Lowrie, J. F.; Dixon, S. L.; Sherman, W. Large-scale systematic analysis of 2D fingerprint methods and parameters to improve virtual screening enrichments J. Chem. Inf. Model. 2010, 50, 771-784
46. Gasteiger, J.; Marsili, M. Iterative Partial Equalization of Orbital Electronegativity-A Rapid Access to Atomic Charges Tetrahedron 1980, 36, 3219-3228
47. Willett, P. Similarity searching using 2D structural fingerprints Methods Mol. Biol. 2010, 672, 133-158
48. Brooijmans, N.; Kuntz, I. D. Molecular recognition and docking algorithms Annu. Rev. Biophys. Biomol. Struct. 2003, 32, 335-373
49. Hopkins, A. L.; Groom, C. R.; Alex, A. Ligand efficiency: a useful metric for lead selection Drug Discovery Today 2004, 9, 430-431
50. Freundlich, J. S.; Anderson, J. W.; Sarantakis, D.; Shieh, H. M.; Yu, M.; Valderramos, J. C.; Lucumi, E.; Kuo, M.; Jacobs, W. R., Jr.; Fidock, D. A.; Schiehser, G. A.; Jacobus, D. P.; Sacchettini, J. C. Synthesis, biological activity, and X-ray crystal structural analysis of diaryl ether inhibitors of malarial enoyl acyl carrier protein reductase. Part 1: 4′-substituted triclosan derivatives Bioorg. Med. Chem. Lett. 2005, 15, 5247-5252
51. Bissantz, C.; Kuhn, B.; Stahl, M. A medicinal chemists guide to molecular interactions J. Med. Chem. 2010, 53, 5061-5084
52. Wagner, A. B. SciFinder Scholar 2006: an empirical analysis of research topic query processing J. Chem. Inf. Model. 2006, 46, 767-774
53. Huffenberger, M. A.; Wigington, R. L. Chemical Abstracts Service approach to management of large data bases J. Chem. Inf. Comput. Sci. 1975, 15, 43-47
54. Qin, A.; Scott, D. W.; Mann, B. J. Francisella tularensis subsp. tularensis Schu S4 disulfide bond formation protein B, but not an RND-type efflux pump, is required for virulence Infect. Immun. 2008, 76, 3086-3092
55. Gil, H.; Platz, G. J.; Forestal, C. A.; Monfett, M.; Bakshi, C. S.; Sellati, T. J.; Furie, M. B.; Benach, J. L.; Thanassi, D. G. Deletion of TolC orthologs in Francisella tularensis identifies roles in multidrug resistance and virulence Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 12897-12902
56. Huang, N.; Shoichet, B. K.; Irwin, J. J. Benchmarking sets for molecular docking J. Med. Chem. 2006, 49, 6789-6801