Discovery and characterization of QPT-1, the progenitor of a new class of bacterial topoisomerase inhibitors

Antimicrobial Agents and Chemotherapy

Volumn 52, Issue 8, 2008, Pages 2806-2812

  Miller, Alita A ^a   Bundy, Gordon L ^a   Mott, John E ^a   Skepner, Jill E ^a   Boyle, Timothy P ^a   Harris, Douglas W ^a   Hromockyj, Alexander E ^a   Marotti, Keith R ^a   Zurenko, Gary E ^a,b   Munzner, Jennifer B ^a   Sweeney, Michael T ^a   Bammert, Gary F ^a   Hamel, Judith C ^a   Ford, Charles W ^a   Zhong, Wei Zhu ^a   Graber, David R ^a   Martin, Gary E ^a,c   Han, Fusen ^a,d   Dolak, Lester A ^a   Seest, Eric P ^a,e   Ruble, J Craig ^a,e   Kamilar, Gregg M ^a,f   Palmer, John R ^a,e   Banitt, Lee S ^a,e   Hurd, Alexander R ^a,g   Barbachyn, Michael R ^a,h   more..

^a PFIZER INC   (United States)

^b Micromyx   (United States)

^c MERCK RESEARCH LABORATORIES   (United States)

^d Tiens Biotech Group   (China)

^e ELI LILLY AND COMPANY   (United States)

^f PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United States)

^g 930 N University   (United States)

^h ASTRAZENECA   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

AMPICILLIN; CHLORAMPHENICOL; CIPROFLOXACIN; DNA TOPOISOMERASE (ATP HYDROLYSING); DNA TOPOISOMERASE INHIBITOR; ERYTHROMYCIN; KANAMYCIN; LINEZOLID; NALIDIXIC ACID; NEOMYCIN; NORFLOXACIN; NOVOBIOCIN; QPT 1; QUINOLINE DERIVED ANTIINFECTIVE AGENT; RIFAMPICIN; SPECTINOMYCIN; STREPTOMYCIN; TETRACYCLINE; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBACTERIAL ACTIVITY; ARTICLE; BACTERIAL INFECTION; BACTERIUM; ENANTIOMER; EUKARYOTIC CELL; FEMALE; GENOMICS; HIGH THROUGHPUT SCREENING; MOUSE; NONHUMAN; PRIORITY JOURNAL;

ANIMALS; ANTI-BACTERIAL AGENTS; AREA UNDER CURVE; BACTERIA; BACTERIAL INFECTIONS; BACTERIAL PROTEINS; CELL LINE; CELL PROLIFERATION; DNA TOPOISOMERASES, TYPE II; METABOLIC CLEARANCE RATE; MICE; MICROBIAL SENSITIVITY TESTS; MOLECULAR STRUCTURE; STAPHYLOCOCCUS AUREUS; STEREOISOMERISM;

EID: 48749117988     PISSN: 00664804     EISSN: None     Source Type: Journal    
DOI: 10.1128/AAC.00247-08     Document Type: Article

References (28)

1. Andries, K., P. Verhasselt, J. Guillemont, H. W. Gohlmann, J. M. Neefs, H. Winkler, J. Van Gestel, P. Timmerman, M. Zhu, E. Lee, P. Williams, D. de Chaffoy, E. Huitric, S. Hoffner, E. Cambay, C. Truffot-Pernot, N. Lounis, and V. Jarlier. 2005. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science 307:223-227.
2. Artsimovitch, I., C. Clement, A. S. Lynch, and R. A. Landick. 2003. New class of bacterial RNA polymerase inhibitor affects nucleotide addition. Science 24:650-654.
3. Barbachyn, M. R., G. L. Bundy, P. J. Dobrowolski, A. R. Hurd, A. R. Romero, D. J. McNamara, J. R. Palmer, L. M. Thomasco, P. L. Toogood, J. C. Ruble, D. A. Sherry, D. L. Romero, and G. E. Martin. April 2007. Tricyclic tetrahydroquinoline antibacterial agents. U.S. patent 7,208,490 B2.
4. Belanger, A. E., A. Lai, M. A. Brackman, and D. J. Leblanc. 2002. PCR-based ordered genomic libraries: a new approach to drug target identification for Streptococcus pneumoniae. Antimicrob. Agents Chemother. 46:2507-2512.
5. Brown, E. D., and G. D. Wright. 2005. New targets and screening approaches in antimicrobial drug discovery. Chem. Rev. 105:759-774.
6. Ehmann, D. E., J. E. Demeritt, K. G. Hull, and S. L. Fisher. 2004. Biochemical characterization of an inhibitor of Escherichia coli UDP-N-acetyl-muramyl-L-alanine ligase. Biochim. Biophys. Acta 1698:167-174.
7. Ejim, L. J., J. E. Blanchard, K. P. Koteva, R. Sumerfield, N. H. Elowe, J. D. Chechetto, E. D. Brown, M. S. Junop, and G. D. Wright. 2007. Inhibitors of bacterial cystathionine beta-lyase: leads for new antimicrobial agents and probes of enzyme structure and function. J. Med. Chem. 50:755-764.
8. Fujimoto-Nakamura, M., H. Ito, Y. Oyamada, T. Nishino, and J. Yamagishi. 2005. Accumulation of mutations in both gyrB and parE genes is associated with high-level resistance to novobiocin in Staphylococcus aureus. Antimicrob. Agents Chemother. 49:3810-3815.
9. He, X., A. Alian, R. Stroud, and P. R. Ortiz de Montellano. 2006. Pyrrolidine carboxamides as a novel class of inhibitors of enoyl acyl carrier protein reductase from M. tuberculosis. J. Med. Chem. 49:6308-6323.
10. Hooper, D. C. 1998. Bacterial topoisomerases, anti-topoisomerases, and antitopoisomerase resistance. Clin. Infect. Dis. 27:S54-S63.
11. ILAR, Commission of Life Sciences, and National Research Council. 1996. Guide for the Care and Use of Laboratory Animals. National Academy Press, Washington, DC.
12. Ito, H., Y. Hiroaki, M. Bogaki-Shonai, N. Toshiyuki, H. Hattori, and S. Nakamura. 1994. Quinolone resistance mutations in the DNA gyrase gyrA and gyrB genes of Staphylococcus aureus. Antimicrob. Agents Chemother. 38:2014-2023.
13. Jones, C. L., and S. A. Kahn. 1986. Nucleotide sequence of the enterotoxin B gene from Staphylococcus aureus. J. Bacteriol. 166:29-33.
14. Levy, S. B. 2005. Antibiotic resistance - the problem intensifies. Adv. Drug Deliv. Rev. 57:1443-1450.
15. Liu, S., J. S. Chang, J. T. Herberg, M. M. Horng, P. K. Tomich, A. H. Lin, and K. R. Marotti. 2006. Allosteric inhibition of Staphylococcus aureus D-alanine:D-alanine ligase revealed by crystallographic studies. Proc. Natl. Acad. Sci. USA 103:15178-15183.
16. Miller, J. H. 1992. A short course in bacterial genetics: a laboratory manual for Escherichia coli and related bacteria. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, NY.
17. Mwangi, M. M., S. W. Wu, Y. Zhou, K. Sieradzki, H. de Lencastre, P. Richardson, D. Bruce, E. Rubin, E. Myers, E. D. Siggia, and A. Tomasz. 2007. Tracking the in vivo evolution of multi-drug resistance in Staphylococcus aureus by whole-genome sequencing. Proc. Natl. Acad. Sci. USA 104: 9451-9456.
18. National Committee for Clinical Laboratory Standards. 2000. Approved standard M7-A5: methods for dilution antimicrobial susceptibility tests for bacteria that grow aerobically, 5th ed. National Committee for Clinical Laboratory Standards, Wayne, PA.
19. Overby, K. M., and J. F. Barrett. 2005. Antibiotics: where did we go wrong? Drug Discov. Today 10:45-52.
20. Payne, D. J., M. N. Gwynn, D. J. Holmes, and D. L. Pompliano. 2007. Drugs for bad bugs: confronting the challenges of antibacterial discovery. Nat. Rev. Drug Discov. 6:29-40.
21. Peterson, L. R. 2005. Squeezing the antibiotic balloon: the impact of antimicrobial classes on emerging resistance. Clin. Microbiol. Infect. 11(Suppl. 5):4-16.
22. Projan, S. 2003. Why is big pharma getting out of antibacterial drug discovery? Curr. Opin. Microbiol. 6:427-430.
23. Schenk, S., and R. Ladagga. 1992. Improved method for electroporation of Staphylococcus aureus. FEMS Microbiol. Lett. 73:133-138.
24. Shlaes, D. M. 2003. The abandonment of antibacterials: why and wherefore? Curr. Opin. Pharmacol. 3:470-473.
25. Silver, L. L., and K. A. Bostian. 1993. Discovery and development of new antibiotics: the problem of antibiotic resistance. Antimicrob. Agents Chemother. 37:377-383.
26. Stamper, G. F., K. L. Longenecker, E. H. Fry, C. G. Jakob, A. S. Florjancic, Y. G. Gu, D. D. Anderson, C. S. Cooper, T. Zhang, R. F. Clark, Y. Cia, C. L. Black-Schaefer, J. Owen McCall, C. G. Lerner, P. J. Hajduk, B. A. Beutel, and V. S. Stoll. 2006. Structure-based Optimization of MurF inhibitors. Chem. Biol. Drug Des. 67:58-65.
27. Talbot, G. H., J. Bradley, J. E. Edwards, Jr., D. Gilbert, M. Scheld, and G. J. Bartlett. 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.
28. Verboom, W., D. N. Reinhoudt, R. Visser, and S. Harkema. 1984. "tert- Amino effect" in heterocyclic synthesis. Formation of N-heterocycles by ring-closure reactions of substituted 2-vinyl-N,N-dialkylanilines. J. Org. Chem. 49:269-276.