Non-nucleoside inhibitors of BasE, an adenylating enzyme in the siderophore biosynthetic pathway of the opportunistic pathogen Acinetobacter baumannii

Journal of Medicinal Chemistry

Volumn 56, Issue 6, 2013, Pages 2385-2405

  Neres, João ^a   Engelhart, Curtis A ^a,b   Drake, Eric J ^c   Wilson, Daniel J ^a   Fu, Peng ^a   Boshoff, Helena I ^d   Barry, Clifton E ^d   Gulick, Andrew M ^c   Aldrich, Courtney C ^a  

^a UNIVERSITY OF MINNESOTA   (United States)

^b UNIVERSITY OF MINNESOTA   (United States)

^c UNIVERSITY AT BUFFALO   (United States)

^d NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

1 (4 HYDROXYBENZYL) 6 PHENYL 1H PYRAZOLO[3,4 B]PYRIDINE 4 CARBOXYLIC ACID; 1 (4 METHOXYBENZYL) 6 (PHENYLAMINO) 1H PYRAZOLO[3,4 B] PYRIDINE 4 CARBOXYLIC ACID; 1 (4 METHOXYBENZYL) 6 PHENYL 1H PYRAZOLO[3,4 B]PYRIDINE 4 CARBOXYLIC ACID; 1 (PYRIDIN 4 YLMETHYL) 1H PYRAZOL 5 AMINE; 4 HYDROXYMETHYL 6 PHENYL 1 (PYRIDIN 4 YLMETHYL) 1H PYRAZOLO [3,4 B]PYRIDINE; 6 (3 HYDROXYPROPYLAMINO) 1 (PYRIDIN 4 YLMETHYL) 1H PYRAZOLO[3,4 B]PYRIDINE 4 CARBOXYLIC ACID; 6 (4 HYDROXYPHENYL) 1 (PYRIDIN 4 YLMETHYL) 1H PYRAZOLO[3,4 B]PYRIDINE 4 CARBOXYLIC ACID; 6 (BENZYLAMINO) 1 (PYRIDIN 4 YLMETHYL) 1H PYRAZOLO[3,4 B]PYRIDINE 4 CARBOXYLIC ACID; 6 (PHENYLETHYNYL) 1 (PYRIDIN 4 YLMETHYL) 1H PYRAZOLO[3,4 B]PYRIDINE 4 CARBOXYLIC ACID; 6 [4 (OCTYLOXY)PHENYL] 1 (PYRIDIN 4 YLMETHYL) 1H PYRAZOLO[3,4 B]PYRIDINE 4 CARBOXYLIC ACID; 6 ETHYNYL 1 (PYRIDIN 4 YLMETHYL) 1H PYRAZOLO[3,4 B]PYRIDINE 4 CARBOXYLIC ACID; 6 MORPHOLINO 1 (PYRIDIN 4 YLMETHYL) 1H PYRAZOLO[3,4 B]PYRIDINE 4 CARBOXYLIC ACID; 6 OXO 1 (PYRIDIN 4 YLMETHYL) 6,7 DIHYDRO 1H PYRAZOLO[3,4 B]PYRIDINE 4 CARBOXYLIC ACID; 6 PHENYL 1 (PYRIDIN 4 YLMETHYL) 1H INDAZOLE 4 CARBOXYLIC ACID; 6 PHENYL 1 (PYRIDIN 4 YLMETHYL) 1H PYRAZOLO[3,4 B]PYRIDIN 4 AMINE; 6 PHENYL 1 (PYRIDIN 4 YLMETHYL) 1H PYRAZOLO[3,4 B]PYRIDINE 4 CARBOXAMIDE; 6 PHENYL 1 (PYRIDIN 4 YLMETHYL) 1H PYRAZOLO[3,4 B]PYRIDINE 4 CARBOXYLIC ACID; 6 PHENYL 1H PYRAZOLO[3,4 B]PYRIDINE 4 CARBOXYLIC ACID; 6 PHENYL 2 (PYRIDIN 4 YLMETHYL) 2H INDAZOLE 4 CARBOXYLIC ACID; ANTIINFECTIVE AGENT; DIETHYL 2 [5 AMINO 1 (4 METHOXYBENZYL) 1H PYRAZOL 4 YL] 2 HYDROXYSUCCINATE; DIETHYL 2 [5 AMINO 1 (PYRIDIN 4 YLMETHYL) 1H PYRAZOL 4 YL] 2 HYDROXYSUCCINATE; ENZYME; ETHYL 1 (4 METHOXYBENZYL) 6 (TRIFLUOROMETHYLSULFONYLOXY) 1H PYRAZOLO[3,4 B]PYRIDINE 4 CARBOXYLATE; ETHYL 1 (4 METHOXYBENZYL) 6 OXO 6,7 DIHYDRO 1H PYRAZOLO[3,4 B]PYRIDINE 4 CARBOXYLATE; ETHYL 6 OXO 1 (PYRIDIN 4 YLMETHYL) 6,7 DIHYDRO 1H PYRAZOLO[3,4 B]PYRIDINE 4 CARBOXYLATE; ETHYL 6 PHENYL 1 (PYRIDIN 4 YLMETHYL) 1H PYRAZOLO[3,4 B]PYRIDINE 4 CARBOXYLATE; PROTEIN BASE; SIDEROPHORE; UNCLASSIFIED DRUG; UNINDEXED DRUG;

ACINETOBACTER BAUMANNII; ARTICLE; BIOSYNTHESIS; CONTROLLED STUDY; DRUG IDENTIFICATION; DRUG PROTEIN BINDING; DRUG SCREENING; DRUG STRUCTURE; ENZYME ACTIVE SITE; ENZYME SUBSTRATE COMPLEX; HIGH THROUGHPUT SCREENING; NONHUMAN;

ACINETOBACTER BAUMANNII; ANTI-BACTERIAL AGENTS; ENZYME INHIBITORS; MICROBIAL SENSITIVITY TESTS; MODELS, MOLECULAR; PROTEIN CONFORMATION; SIDEROPHORES; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84875696130     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm301709s     Document Type: Article

References (65)

1. Projan, S. J.; Bradford, P. A. Late stage antibacterial drugs in the clinical pipeline Curr. Opin. Microbiol. 2007, 10, 441-446
2. Wright, G. D. Antibiotics: a new hope Chem. Biol. 2012, 19, 3-10
3. Peleg, A. Y.; Seifert, H.; Paterson, D. L. Acinetobacter baumannii: emergence of a successful pathogen Clin. Microbiol. Rev. 2008, 21, 538-582
4. Calhoun, J. H.; Murray, C. K.; Manring, M. M. Multidrug-resistant organisms in military wounds from Iraq and Afghanistan Clin. Orthop. Relat. Res. 2008, 466, 1356-1362
5. Lockhart, S. R.; Abramson, M. A.; Beekmann, S. E.; Gallagher, G.; Riedel, S.; Diekema, D. J.; Quinn, J. P.; Doern, G. V. Antimicrobial resistance among Gram-negative bacilli causing infections in intensive care unit patients in the United States between 1993 and 2004 J. Clin. Microbiol. 2007, 45, 3352-3359
6. Rhomberg, P. R.; Jones, R. N. Summary trends for the Meropenem Yearly Susceptibility Test Information Collection Program: a 10-year experience in the United States (1999-2008) Diagn. Microbiol. Infect. Dis. 2009, 65, 414-426
7. Vallenet, D.; Nordmann, P.; Barbe, V.; Poirel, L.; Mangenot, S.; Bataille, E.; Dossat, C.; Gas, S.; Kreimeyer, A.; Lenoble, P.; Oztas, S.; Poulain, J.; Segurens, B.; Robert, C.; Abergel, C.; Claverie, J. M.; Raoult, D.; Medigue, C.; Weissenbach, J.; Cruveiller, S. Comparative analysis of Acinetobacters: three genomes for three lifestyles PLoS One 2008, 3, e1805
8. Adams, M. D.; Goglin, K.; Molyneaux, N.; Hujer, K. M.; Lavender, H.; Jamison, J. J.; MacDonald, I. J.; Martin, K. M.; Russo, T.; Campagnari, A. A.; Hujer, A. M.; Bonomo, R. A.; Gill, S. R. Comparative genome sequence analysis of multidrug-resistant Acinetobacter baumannii J. Bacteriol. 2008, 190, 8053-8064
9. Falagas, M. E.; Kasiakou, S. K. Colistin: the revival of polymyxins for the management of multidrug-resistant Gram-negative bacterial infections Clin. Infect. Dis. 2005, 40, 1333-1341
10. Cai, Y.; Chai, D.; Wang, R.; Liang, B.; Bai, N. Colistin resistance of Acinetobacter baumannii: clinical reports, mechanisms and antimicrobial strategies J. Antimicrob. Chemother. 2012, 67, 1607-1615
11. Posey, J. E.; Gherardini, F. C. Lack of a role for iron in the lyme disease pathogen Science 2000, 288, 1651-1653
12. Miethke, M.; Marahiel, M. A. Siderophore-based iron acquisition and pathogen control Microbiol. Mol. Biol. Rev. 2007, 71, 413-451
13. Crosa, J. H.; Walsh, C. T. Genetics and assembly line enzymology of siderophore biosynthesis in bacteria Microbiol. Mol. Biol. Rev. 2002, 66, 223-249
14. Sandy, M.; Butler, A. Microbial iron acquisition: marine and terrestrial siderophores Chem. Rev. 2009, 109, 4580-4595
15. Hider, R. C.; Kong, X. Chemistry and biology of siderophores Nat. Prod. Rep. 2010, 27, 637-657
16. Zimbler, D. L.; Penwell, W. F.; Gaddy, J. A.; Menke, S. M.; Tomaras, A. P.; Connerly, P. L.; Actis, L. A. Iron acquisition functions expressed by the human pathogen Acinetobacter baumannii BioMetals 2009, 22, 23-32
17. Lawlor, M. S.; O'Connor, C.; Miller, V. L. Yersiniabactin is a virulence factor for Klebsiella pneumoniae during pulmonary infection Infect. Immun. 2007, 75, 1463-1472
18. Takase, H.; Nitanai, H.; Hoshino, K.; Otani, T. Impact of siderophore production on Pseudomonas aeruginosa infections in immunosuppressed mice Infect. Immun. 2000, 68, 1834-1839
19. Fischbach, M. A.; Lin, H.; Zhou, L.; Yu, Y.; Abergel, R. J.; Liu, D. R.; Raymond, K. N.; Wanner, B. L.; Strong, R. K.; Walsh, C. T.; Aderem, A.; Smith, K. D. The pathogen-associated iroA gene cluster mediates bacterial evasion of lipocalin 2 Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 16502-16507
20. Cendrowski, S.; MacArthur, W.; Hanna, P. Bacillus anthracis requires siderophore biosynthesis for growth in macrophages and mouse virulence Mol. Microbiol. 2004, 51, 407-417
21. Dale, S. E.; Doherty-Kirby, A.; Lajoie, G.; Heinrichs, D. E. Role of siderophore biosynthesis in virulence of Staphylococcus aureus: identification and characterization of genes involved in production of a siderophore Infect. Immun. 2004, 72, 29-37
22. De Voss, J. J.; Rutter, K.; Schroeder, B. G.; Su, H.; Zhu, Y.; Barry, C. E., 3rd. The salicylate-derived mycobactin siderophores of Mycobacterium tuberculosis are essential for growth in macrophages Proc. Natl. Acad. Sci. U.S.A. 2000, 97, 1252-1257
23. Kohanski, M. A.; Dwyer, D. J.; Hayete, B.; Lawrence, C. A.; Collins, J. J. A common mechanism of cellular death induced by bactericidal antibiotics Cell 2007, 130, 797-810
24. Dwyer, D. J.; Kohanski, M. A.; Collins, J. J. Role of reactive oxygen species in antibiotic action and resistance Curr. Opin. Microbiol. 2009, 12, 482-489
25. Yamamoto, S.; Okujo, N.; Sakakibara, Y. Isolation and structure elucidation of acinetobactin, a novel siderophore from Acinetobacter baumannii Arch. Microbiol. 1994, 162, 249-254
26. Takeuchi, Y.; Ozaki, S.; Satoh, M.; Mimura, K.; Hara, S.; Abe, H.; Nishioka, H.; Harayama, T. Synthesis of acinetobactin Chem. Pharm. Bull. 2010, 58, 1552-1553
27. Dorsey, C. W.; Tomaras, A. P.; Connerly, P. L.; Tolmasky, M. E.; Crosa, J. H.; Actis, L. A. The siderophore-mediated iron acquisition systems of Acinetobacter baumannii ATCC 19606 and Vibrio anguillarum 775 are structurally and functionally related Microbiology 2004, 150, 3657-3667
28. Mihara, K.; Tanabe, T.; Yamakawa, Y.; Funahashi, T.; Nakao, H.; Narimatsu, S.; Yamamoto, S. Identification and transcriptional organization of a gene cluster involved in biosynthesis and transport of acinetobactin, a siderophore produced by Acinetobacter baumannii ATCC 19606T Microbiology 2004, 150, 2587-2597
29. Sattely, E. S.; Walsh, C. T. A latent oxazoline electrophile for N-O-C bond formation in pseudomonine biosynthesis J. Am. Chem. Soc. 2008, 130, 12282-12284
30. Wuest, W. M.; Sattely, E. S.; Walsh, C. T. Three siderophores from one bacterial enzymatic assembly line J. Am. Chem. Soc. 2009, 131, 5056-5057
31. Drake, E. J.; Duckworth, B. P.; Neres, J.; Aldrich, C. C.; Gulick, A. M. Biochemical and structural characterization of bisubstrate inhibitors of BasE, the self-standing nonribosomal peptide synthetase adenylate-forming enzyme of acinetobactin synthesis Biochemistry 2010, 49, 9292-9305
32. Hurdle, J. G.; O'Neill, A. J.; Chopra, I. Prospects for aminoacyl-tRNA synthetase inhibitors as new antimicrobial agents Antimicrob. Agents Chemother. 2005, 49, 4821-4833
33. Sikora, A. L.; Wilson, D. J.; Aldrich, C. C.; Blanchard, J. S. Kinetic and inhibition studies of dihydroxybenzoate-AMP ligase from Escherichia coli Biochemistry 2010, 49, 3648-3657
34. Gulick, A. M. Conformational dynamics in the Acyl-CoA synthetases, adenylation domains of non-ribosomal peptide synthetases, and firefly luciferase ACS Chem. Biol. 2009, 4, 811-827
35. Ferreras, J. A.; Ryu, J. S.; Di Lello, F.; Tan, D. S.; Quadri, L. E. Small-molecule inhibition of siderophore biosynthesis in Mycobacterium tuberculosis and Yersinia pestis Nat. Chem. Biol. 2005, 1, 29-32
36. Somu, R. V.; Boshoff, H.; Qiao, C. H.; Bennett, E. M.; Barry, C. E.; Aldrich, C. C. Rationally designed nucleoside antibiotics that inhibit siderophore biosynthesis of Mycobacterium tuberculosis J. Med. Chem. 2006, 49, 31-34
37. Miethke, M.; Bisseret, P.; Beckering, C. L.; Vignard, D.; Eustache, J.; Marahiel, M. A. Inhibition of aryl acid adenylation domains involved in bacterial siderophore synthesis FEBS J. 2006, 273, 409-419
38. Somu, R. V.; Wilson, D. J.; Bennett, E. M.; Boshoff, H. I.; Celia, L.; Beck, B. J.; Barry, C. E.; Aldrich, C. C. Antitubercular nucleosides that inhibit siderophore biosynthesis: SAR of the glycosyl domain J. Med. Chem. 2006, 49, 7623-7635
39. Neres, J.; Wilson, D. J.; Celia, L.; Beck, B. J.; Aldrich, C. C. Aryl acid adenylating enzymes involved in siderophore biosynthesis: fluorescence polarization assay, ligand specificity, and discovery of non-nucleoside inhibitors via high-throughput screening Biochemistry 2008, 47, 11735-11749
40. Hohn, H. Ein neue Verfahren zur Darstellung von 5-Aminopyrazolen Z. Chem. 1970, 10, 386-388
41. Dorn, H.; Müller, T. Zur direkten (C-4)-substitution von Amino-Pyrazolen mit β-keto-carbonyl-Verbindungen-1-Benzyl-6, 7-dihydro-4-ethoxycarbonyl-6-oxo-pyrazolo[3,4- b ]pyridin Z. Chem. 1980, 20, 95
42. Kang, F. A.; Sui, Z. H.; Murray, W. V. Pd-catalyzed direct arylation of tautomerizable heterocycles with aryl boronic acids via C-OH bond activation using phosphonium salts J. Am. Chem. Soc. 2008, 130, 11300-11302
43. Wan, Z. K.; Wacharasindhu, S.; Levins, C. G.; Lin, M.; Tabei, K.; Mansour, T. S. The scope and mechanism of phosphonium-mediated S(N)Ar reactions in heterocyclic amides and ureas J. Org. Chem. 2007, 72, 10194-10210
44. Gupte, A.; Boshoff, H. I.; Wilson, D. J.; Neres, J.; Labello, N. P.; Somu, R. V.; Xing, C.; Barry, C. E.; Aldrich, C. C. Inhibition of siderophore biosynthesis by 2-triazole substituted analogues of 5′- O -[ N -(salicyl)sulfamoyl]adenosine: antibacterial nucleosides effective against Mycobacterium tuberculosis J. Med. Chem. 2008, 51, 7495-7507
45. Shi, C.; Aldrich, C. C. Efficient Pd-catalyzed coupling of tautomerizable heterocycles with terminal alkynes via C-OH bond activation using PyBroP Org. Lett. 2010, 12, 2286-2289
46. Roehrl, M. H. A.; Wang, J. Y.; Wagner, G. A general framework for development and data analysis of competitive high-throughput screens for small-molecule inhibitors of protein-protein interactions by fluorescence polarization Biochemistry 2004, 43, 16056-16066
47. Stachelhaus, T.; Mootz, H. D.; Marahiel, M. A. The specificity-conferring code of adenylation domains in nonribosomal peptide synthetases Chem. Biol. 1999, 6, 493-505
48. Auld, D. S.; Lovell, S.; Thorne, N.; Lea, W. A.; Maloney, D. J.; Shen, M.; Rai, G.; Battaile, K. P.; Thomas, C. J.; Simeonov, A.; Hanzlik, R. P.; Inglese, J. Molecular basis for the high-affinity binding and stabilization of firefly luciferase by PTC124 Proc. Natl. Acad. Sci. U.S.A. 2010, 107, 4878-4883
49. Lee, T. V.; Johnson, L. J.; Johnson, R. D.; Koulman, A.; Lane, G. A.; Lott, J. S.; Arcus, V. L. Structure of a eukaryotic nonribosomal peptide synthetase adenylation domain that activates a large hydroxamate amino acid in siderophore biosynthesis J. Biol. Chem. 2010, 285, 2415-2427
50. Gordon, N. C.; Wareham, D. W. Multidrug-resistant Acinetobacter baumannii: mechanisms of virulence and resistance Int. J. Antimicrob. Agents 2010, 35, 219-226
51. Quadri, L. E. Strategic paradigm shifts in the antimicrobial drug discovery process of the 21st century Infect. Disord. Drug Targets 2007, 7, 230-237
52. Frederick, R. E.; Mayfield, J. A.; DuBois, J. L. Iron trafficking as an antimicrobial target BioMetals 2009, 22, 583-593
53. Ballouche, M.; Cornelis, P.; Baysse, C. Iron metabolism: a promising target for antibacterial strategies Recent Pat. Anti-Infect. Drug Discovery 2009, 4, 190-205
54. Cescau, S.; Cwerman, H.; Letoffe, S.; Delepelaire, P.; Wandersman, C.; Biville, F. Heme acquisition by hemophores BioMetals 2007, 20, 603-613
55. Budzikiewicz, H. Microbial Siderophores; Spinger-Verlag: Vienna, Austria, 2010; Vol. 92, p 75.
56. Fischbach, M. A.; Walsh, C. T. Antibiotics for emerging pathogens Science 2009, 325, 1089-1093
57. Adler, C.; Corbalan, N. S.; Seyedsayamdost, M. R.; Pomares, M. F.; de Cristobal, R. E.; Clardy, J.; Kolter, R.; Vincent, P. A. Catecholate siderophores protect bacteria from pyochelin toxicity PLoS One 2012, 7, e46754
58. Dorsey, C. W.; Tolmasky, M. E.; Crosa, J. H.; Actis, L. A. Genetic organization of an Acinetobacter baumannii chromosomal region harbouring genes related to siderophore biosynthesis and transport Microbiology 2003, 149, 1227-1238
59. Penwell, W. F.; Arivett, B. A.; Actis, L. A. The Acinetobacter baumannii entA gene located outside the acinetobactin cluster is critical for siderophore production, iron acquisition and virulence PLoS One 2012, 7, e36493
60. Gaddy, J. A.; Arivett, B. A.; McConnell, M. J.; Lopez-Rojas, R.; Pachon, J.; Actis, L. A. Role of acinetobactin-mediated iron acquisition functions in the interaction of Acinetobacter baumannii strain ATCC 19606T with human lung epithelial cells, Galleria mellonella caterpillars, and mice Infect. Immun. 2012, 80, 1015-1024
61. Eijkelkamp, B. A.; Hassan, K. A.; Paulsen, I. T.; Brown, M. H. Investigation of the human pathogen Acinetobacter baumannii under iron limiting conditions BMC Genomics 2011, 12, 126
62. Antunes, L. C.; Imperi, F.; Towner, K. J.; Visca, P. Genome-assisted identification of putative iron-utilization genes in Acinetobacter baumannii and their distribution among a genotypically diverse collection of clinical isolates Res. Microbiol. 2011, 162, 279-284
63. Misra, R. N.; Rawlins, D. B.; Xiao, H. Y.; Shan, W. F.; Bursuker, I.; Kellar, K. A.; Mulheron, J. G.; Sack, J. S.; Tokarski, J. S.; Kimball, S. D.; Webster, K. R. 1 H -Pyrazolo[3,4- b ]pyridine inhibitors of cyclin-dependent kinases Bioorg. Med. Chem. Lett. 2003, 13, 1133-1136
64. Higgins, P. G.; Poirel, L.; Lehmann, M.; Nordmann, P.; Seifert, H. OXA-143, a novel carbapenem-hydrolyzing class D beta-lactamase in Acinetobacter baumannii Antimicrob. Agents Chemother. 2009, 53, 5035-5038
65. Choi, K. H.; Kumar, A.; Schweizer, H. P. A 10-min method for preparation of highly electrocompetent Pseudomonas aeruginosa cells: application for DNA fragment transfer between chromosomes and plasmid transformation J. Microbiol. Methods 2006, 64, 391-397