Discovery of novel bacterial RNA polymerase inhibitors: Pharmacophore-based virtual screening and hit optimization

Journal of Medicinal Chemistry

Volumn 56, Issue 21, 2013, Pages 8332-8338

  Hinsberger, Stefan ^a   Hüsecken, Kristina ^a   Groh, Matthias ^a   Negri, Matthias ^a   Haupenthal, Jörg ^a   Hartmann, Rolf W ^a,b  

^a SAARLAND UNIVERSITY   (Germany)

^b SAARLAND UNIVERSITY   (Germany)

Author keywords

[No Author keywords available]

Indexed keywords

ANTHRANILIC ACID; ANTIBIOTIC AGENT; BACTERIAL RNA POLYMERASE INHIBITOR; UNCLASSIFIED DRUG;

ANTIBACTERIAL ACTIVITY; ARTICLE; BACILLUS SUBTILIS; BACTERIAL GROWTH; CONTROLLED STUDY; DRUG POTENCY; DRUG SCREENING; DRUG SYNTHESIS; ESCHERICHIA COLI; IN VITRO STUDY; LIPOGENESIS; LIPOPHILICITY; MINIMUM INHIBITORY CONCENTRATION; NONHUMAN; PHARMACOPHORE; PROTEIN PROTEIN INTERACTION; PSEUDOMONAS AERUGINOSA; STAPHYLOCOCCUS AUREUS; STRUCTURE ACTIVITY RELATION;

ANTI-BACTERIAL AGENTS; BACILLUS SUBTILIS; DNA-DIRECTED RNA POLYMERASES; DOSE-RESPONSE RELATIONSHIP, DRUG; DRUG DISCOVERY; ENZYME INHIBITORS; ESCHERICHIA COLI; HIGH-THROUGHPUT SCREENING ASSAYS; MICROBIAL SENSITIVITY TESTS; MODELS, MOLECULAR; MOLECULAR STRUCTURE; PSEUDOMONAS AERUGINOSA; STAPHYLOCOCCUS AUREUS; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 84887872346     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/jm400485e     Document Type: Article

References (22)

1. Hooper, D. C.; DeMaria, A.; Limbago, B. M.; O'Brien, T. F.; McCaughey, B. Antibiotic resistance: how serious is the problem, and what can be done? Clin. Chem. 2012, 58, 1182-1186
2. Chopra, I. The 2012 Garrod Lecture: Discovery of Antibacterial Drugs in the 21st Century J. Antimicrob. Chemother. 2013, 68, 496-505
3. Villain-Guillot, P.; Bastide, L.; Gualtieri, M.; Leonetti, J.-P. Progress in targeting bacterial transcription Drug Discovery Today 2007, 12, 200-208
4. Ho, M. X.; Hudson, B. P.; Das, K.; Arnold, E.; Ebright, R. H. Structures of RNA polymerase-antibiotic complexes Curr. Opin. Struct. Biol. 2009, 19, 715-723
5. Hardesty, J. S.; Juang, P. Fidaxomicin: a macrocyclic antibiotic for the treatment of Clostridium difficile infection Pharmacotherapy 2011, 31, 877-886
6. Mariani, R.; Maffiolo, S. I. Bacterial RNA polymerase inhibitors: an organized overview of their structure, derivatives, biological activity and current clinical development status Curr. Med. Chem. 2009, 16, 430-454
7. Chopra, I. Bacterial RNA polymerase: a promising target for the discovery of new antimicrobial agents Curr. Opin. Invest. Dr. 2007, 8, 600-607
8. Arhin, F.; Bélanger, O.; Ciblat, S.; Dehbi, M.; Delorme, D.; Dietrich, E.; Dixit, D.; Lafontaine, Y.; Lehoux, D.; Liu, J.; McKay, G. A.; Moeck, G.; Reddy, R.; Rose, Y.; Srikumar, R.; Tanaka, K. S. E.; Williams, D. M.; Gros, P.; Pelletier, J.; Parr, T. R., Jr.; Far, A. R. A new class of small molecule RNA polymerase inhibitors with activity against rifampicin-resistant Staphylococcus aureus Bioorg. Med. Chem. 2006, 14, 5812-5832
9. Artsimovitch, I.; Chu, C.; Lynch, A. S.; Landick, R. A new class of bacterial RNA polymerase inhibitor affects nucleotide addition Science 2003, 302, 650-654
10. André, E.; Bastide, L.; Michaux-Charachon, S.; Gouby, A.; Villain-Guillot, P.; Latouche, J.; Bouchet, A.; Gualtiéri, M.; Leonetti, J.-P. Novel synthetic molecules targeting the bacterial RNA polymerase assembly J. Antimicrob. Chemother. 2006, 57, 245-251
11. Villain-Guillot, P.; Gualtieri, M.; Bastide, L.; Roquet, F. o.; Martinez, J.; Amblard, M.; Pugniere, M.; Leonetti, J.-P. Structure-Activity Relationships of phenyl-furanyl-rhodanines as inhibitors of RNA polymerase with antibacterial activity on biofilms J. Med. Chem. 2007, 50, 4195-4204
12. Larsen, S. D.; Hester, M. R.; Craig Ruble, J.; Kamilar, G. M.; Romero, D. L.; Wakefield, B.; Melchior, E. P.; Sweeney, M. T.; Marotti, K. R. Discovery and initial development of a novel class of antibacterials: Inhibitors of Staphylococcus aureus transcription/translation Bioorg. Med. Chem. Lett. 2006, 16, 6173-6177
13. Haupenthal, J.; Hüsecken, K.; Negri, M.; Maurer, C. K.; Hartmann, R. W. Influence of DNA template choice on transcription and inhibition of Escherichia coli RNA polymerase Antimicrob. Agents Chemother. 2012, 56, 4536-4539
14. 70: core interface as target site ACS Chem. Biol. 2013, 8, 758-766
15. Thornsberry, C.; Hill, B. C.; Swenson, J. M.; McDougal, L. K. Rifampin: spectrum of antibacterial activity Rev. Infect. Dis. 1983, 5, 412-417
16. Bandow, J. E.; Brötz, H.; Hecker, M. Bacillus subtilis tolerance of moderate concentrations of Rifampin involves the sigma(B)-dependent general and multiple stress response J. Bacteriol. 2002, 184, 459-467
17. Fowler, C. E.; Soothill, J. S.; Oakes, L. MICs of rifampicin and chloramphenicol for mucoid Pseudomonas aeruginosa strains are lower when human lactoferrin is present J. Antimicrob. Chemother. 1997, 40, 877-879
18. Williams, K. J.; Piddock, L. J. Accumulation of rifampicin by Escherichia coli and Staphylococcus aureus J. Antimicrob. Chemother. 1998, 42, 597-603
19. Irschik, H.; Gerth, K.; Höfle, G.; Kohl, W.; Reichenbach, H. The myxopyronins, new inhibitors of bacterial RNA synthesis from Myxococcus fulvus (Myxobacterales) J. Antibiot. 1983, 36, 1651-1658
20. Pistorius, D.; Ullrich, A.; Lucas, S.; Hartmann, R. W.; Kazmaier, U.; Müller, R. Biosynthesis of 2-alkyl-4(1 H)-quinolones in Pseudomonas aeruginosa: potential for therapeutic interference with pathogenicity ChemBioChem 2011, 12, 850-853
21. Nie, Z.; Perretta, C.; Lu, J.; Su, Y.; Margosiak, S.; Gajiwala, K. S.; Cortez, J.; Nikulin, V.; Yager, K. M.; Appelt, K.; Chu, S. Structure-based design, synthesis, and study of potent inhibitors of β-ketoacyl-acyl carrier protein synthase III as potential antimicrobial agents J. Med. Chem. 2005, 48, 1596-1609
22. Sahner, J. H.; Groh, M.; Negri, M.; Haupenthal, J.; Hartmann, R. W. Novel small molecule inhibitors targeting the "switch region" of bacterial RNAP: structure-based optimization of a virtual screening hit Eur. J. Med. Chem. 2013, 65, 223-231