Pyrrolamide DNA gyrase inhibitors: Fragment-based nuclear magnetic resonance screening to identify antibacterial agents

Antimicrobial Agents and Chemotherapy

Volumn 56, Issue 3, 2012, Pages 1240-1246

  Eakin, Ann E ^a   Green, Oluyinka ^a   Hales, Neil ^a   Walkup, Grant K ^a   Bist, Shanta ^a   Singh, Alok ^a   Mullen, George ^a   Bryant, Joanna ^a   Embrey, Kevin ^a   Gao, Ning ^a   Breeze, Alex ^a   Timms, Dave ^a   Andrews, Beth ^a   Uria Nickelsen, Maria ^a   Demeritt, Julie ^a   Loch III, James T ^a   Hull, Ken ^a   Blodgett, April ^a   Illingworth, Ruth N ^a   Prince, Bryan ^a   Boriack Sjodin, P Ann ^a   Hauck, Sheila ^a   MacPherson, Lawrence J ^a   Ni, Haihong ^a   Sherer, Brian ^a   more..

^a ASTRAZENECA   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

AGAR; ANTIINFECTIVE AGENT; DNA TOPOISOMERASE (ATP HYDROLYSING); GYRASE INHIBITOR; PYRROLAMIDE; PYRROLE; UNCLASSIFIED DRUG;

ANTIBACTERIAL ACTIVITY; ANTIBIOTIC RESISTANCE; ARTICLE; BACTERIAL GENE; BACTERIAL STRAIN; BACTERIUM ISOLATE; CONTROLLED STUDY; DNA SEQUENCE; DRUG ACTIVITY; DRUG BINDING; DRUG EFFICACY; DRUG POTENCY; DRUG SYNTHESIS; GENETIC VARIABILITY; IC 50; MINIMUM INHIBITORY CONCENTRATION; MOLECULAR WEIGHT; NONHUMAN; NUCLEAR MAGNETIC RESONANCE IMAGING; POINT MUTATION; PRIORITY JOURNAL; STAPHYLOCOCCUS AUREUS; X RAY CRYSTALLOGRAPHY;

AMIDES; ANIMALS; ANTI-BACTERIAL AGENTS; BINDING SITES; CRYSTALLOGRAPHY, X-RAY; DNA GYRASE; DRUG RESISTANCE, BACTERIAL; ENZYME INHIBITORS; HUMANS; INHIBITORY CONCENTRATION 50; MAGNETIC RESONANCE SPECTROSCOPY; MICE; MICROBIAL SENSITIVITY TESTS; MODELS, MOLECULAR; MUTATION; PROTEIN BINDING; PYRROLES; STAPHYLOCOCCAL INFECTIONS; STAPHYLOCOCCUS AUREUS; STREPTOCOCCUS PNEUMONIAE;

EID: 84863393500     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.05485-11     Document Type: Article

References (28)

1. Alanis AJ. 2005. Resistance to antibiotics: Are we in the post-antibiotic era? Arch. Med. Res. 36:697-707.
2. Albert JS, et al. 2007. An integrated approach to fragment-based lead generation: philosophy, strategy and case studies from AstraZeneca's drug discovery programmes. Curr. Top. Med. Chem. 7:1600-1629. (Pubitemid 350131017)
3. Azoulay-Dupuis E, Vallee E, Hardy DJ, Swanson RN, Pocidalo JJ. 1991. Antipneumococcal activity of ciprofloxacin, ofloxacin, and temafloxacin in an experimental mouse pneumonia model at various stages of disease. J. Infect. Dis. 163:319-324.
4. Biedenbach DJ, Farrell DJ, Mendes RE, Ross JE, Jones RN. 2010. Stability of linezolid activity in the era of mobile oxazolidinone resistance determinants: results from the 2009 Zyvox Annuaj Appraisal of Potency and Spectrum program. Diagn. Microbiol. Infect. Dis. 68:459-467.
5. Boucher HW, et al. 2009. Bad bugs, no drugs: no ESKAPE! An update from the Infectious Diseases Society of America. Clin. Infect. Dis. 48:1-12.
6. Boyd LB, et al. 2008. Increased fluoroquinolone resistance with time in Escherichia coli from >17,000 patients at a large county hospital as a function of culture site, age, sex and location. BMC Infect. Dis. 8:4.
7. de Jonge BLM, Kutschke A, Uria-Nickelsen M, Kamp HD, Mills SD. 2009. Pyrazolopyrimidinediones are selective agents for Helicobacter pylori that suppress growth through inhibition of glutamate racemase (MurI). Antimicrob. Agents Chemother. 53:3331-3336.
8. Drlica K, Malik M, Kerns RJ, Zhao X. 2008. Quinolone-mediated bacterial death. Antimicrob. Agents Chemother. 52:385-392. (Pubitemid 351170804)
9. Dwyer DJ, Kohanski MA, Hayete B, Collins JJ. 2007. Gyrase inhibitors induce an oxidative damage cellular death pathway in Escherichia coli. Mol. Syst. Biol. 3:91-106.
10. Green O, et al. 2008. Novel DNA gyrase inhibitors: structure guided discovery and optimization of pyrrolamides, abstr F1-2025. Abstr. 48th Intersci. Conf. Antimicrob. Agents Chemother. American Society for Microbiology, Washington, DC.
11. Hajduk PJ. 2006. Fragment-based drug discovery: how big is too big? J. Med. Chem. 49:6972-6976. (Pubitemid 44885985)
12. Hopkins AL, Groom CR, Alex A. 2004. Ligand efficiency: a useful metric for lead selection. Drug Discov. Today 9:430-431. (Pubitemid 38510559)
13. Hull K, et al. 2008. Novel DNA gyrase inhibitors: the effect of pyrrolamide variations at site 1 and site 2 upon potency, abstr F1-2027. Abstr. 48th Intersci. Conf. Antimicrob. Agents Chemother. American Society for Microbiology, Washington, DC.
14. Illingworth RN, Uria-Nickelsen M, Bryant J, Eakin AE. 2008. Novel DNA gyrase inhibitors: microbiological characterization and in vivo efficacy of pyrrolamides, abstr F1-2028. Abstr. 48th Intersci. Conf. Antimicrob. Agents Chemother. American Society for Microbiology, Washington, DC.
15. Maxwell A, Lawson DM. 2003. The ATP binding site of type II topoisomerases as a target for antibacterial drugs. Curr. Top. Med. Chem. 3:283-303.
16. Moine P, et al. 1994. In vivo efficacy of a broad-spectrum cephalosporin, ceftriaxone, against penicillin-susceptible and -resistant strains of Streptococcus pneumoniae in a mouse model. Antimicrob. Agents Chemother. 380:1953-1958. (Pubitemid 24278784)
17. National Committee for Clinical Laboratory Standards. 1997. Reference method for broth dilution antifungal susceptibility testing of yeasts. Approved standard M27-A. National Committee for Clinical Laboratory Standards, Wayne, PA.
18. National Committee for Clinical Laboratory Standards. 2005. Methods for determining bacteriocidal activity of antimicrobial agents, vol 12, no 9. Approved Standard M26. National Committee for Clinical Laboratory Standards, Wayne, PA.
19. National Committee for Clinical Laboratory Standards. 2009. Methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 8th ed, vol 29, no 2. Approved standard M07-A8. National Committee for Clinical Laboratory Standards, Wayne, PA.
20. Payne DJ, Gwynn MN, Holmes DJ, Pompliano DL. 2007. Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat. Rev. Drug Discov. 6:29-40. (Pubitemid 46020284)
21. Rhomberg PR, Jones RN. 2009. Summary trends for the meropenem yearly susceptibility test information collection program: a 10-year experience in the United States (1999-2009). Diagn. Microbiol. Infect. Dis. 65:414-426.
22. Sherer B, et al. 2008. Novel DNA gyrase inhibitors: the effect of pyrrolamide linker variations upon potency, abstr F1-2026. Abstr. 48th Intersci. Conf. Antimicrob. Agents Chemother. American Society for Microbiology, Washington, DC.
23. Shuker SB, Hajduk PJ, Meadows RP, Fesik SW. 1996. Discovering high-affinity ligands for proteins: SAR by NMR. Science 274:1531-1534. (Pubitemid 26403929)
24. Talbot GH, et al. 2006. Bad bugs need drugs: an update on the development pipeline from the Antimicrobial Availability Task Force of the Infectious Diseases Society of America. Clin. Infect. Dis. 42:657-668. (Pubitemid 43271379)
25. Tsai et al. 1997. The high-resolution crystal structure of a 24-kDa gyrase B fragment from Escherichia coli complexed with one of the most potent coumarin inhibitors, clorobiocin. Proteins 28:41-52. (Pubitemid 27194017)
26. Uria-Nickelsen M, Blodgett A, Eakin AE. 2008. Novel DNA gyrase inhibitors: investigation of the mechanism of action of pyrrolamides, abstr F1-2029. Abstr. 48th Intersci. Conf. Antimicrob. Agents Chemother. American Society for Microbiology, Washington, DC.
27. Wang JC. 2009. Untangling the double helix: DNA entanglement and the action of the DNA topoisomerases. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
28. Wigley DB, Davies GJ, Dodson EJ, Maxwell A, Dodson G. 1991. Crystal structure of an N-terminal fragment of the DNA gyrase B protein. Nature 351:624-629. (Pubitemid 21896650)