Identification of New Enterococcus faecalis Peptide Deformylase Inhibitors

Author(s): Amina Merzoug*, Abdelouahab Chikhi, Abderrahmane Bensegueni, Hanane Boucherit, Sawsen Hadef.

Journal Name: Current Enzyme Inhibition

Volume 15 , Issue 2 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Aim and Objective: The antibacterial therapy resistance poses an urgent threat to the public’s health. Peptide deformylase is a favorable target to identify new antibiotics with novel mechanism of action.

Materials and Methods: In order to discovery new potent inhibitors of this enzyme, the virtual screening method of Zinc database using the binding site of Enterococcus faecalis peptide deformylase combined with microbiological assay were realized.

Results: The strategy undertaken in this study allowed us to identify new products with growth inhibition activity. The best result was obtained for the chemicals 4-(1,3-dioxo-1Hbenzo[de]isoquinolin- 2(3H)-yl)-N-hydroxybutanamide and N-hydroxy-2-(3-oxo-3,4-dihydro-2H-1,4-benzothiazin-2-yl) acetamide, they showed good affinities and great antibacterial activities compared to the other studied products.

Conclusion: The two most promising compounds can serve as potential antibacterial agents.

Keywords: Antibacterial activity, binding affinity, Enterococcus faecalis, peptide deformylase, virtual screening, ZINC database.

[1]
Conceição, N.; da Silva, L.E.; Darini, A.L.; Pitondo-Silva, A.; de Oliveira, A.G. Penicillin-resistant, ampicillin-susceptible Enterococcus faecalis of hospital origin: pbp4 gene polymorphism and genetic diversity. Infect. Genet. Evol., 2014, 28, 289-295.
[http://dx.doi.org/10.1016/j.meegid.2014.10.018] [PMID: 25445645]
[2]
O’Dwyer, K.; Hackel, M.; Hightower, S.; Hoban, D.; Bouchillon, S.; Qin, D.; Aubart, K.; Zalacain, M.; Butler, D. Comparative analysis of the antibacterial activity of a novel peptide deformylase inhibitor, GSK1322322. Antimicrob. Agents Chemother., 2013, 57(5), 2333-2342.
[http://dx.doi.org/10.1128/AAC.02566-12] [PMID: 23478958]
[3]
Merzoug, A.; Lalaoui, M.; Matoug, S.; Chikhi, A.; Bensegueni, A.; Boucherit, H. Research of new anti-tuberculosis agents by molecular docking’s method. J. Comput. Methods Mol. Des., 2016, 6(2), 20-28.
[4]
Solbiati, J.; Chapman-Smith, A.; Miller, J.L.; Miller, C.G.; Cronan, J.E., Jr Processing of the N termini of nascent polypeptide chains requires deformylation prior to methionine removal. J. Mol. Biol., 1999, 290(3), 607-614.
[http://dx.doi.org/10.1006/jmbi.1999.2913] [PMID: 10395817]
[5]
Guilloteau, J.P.; Mathieu, M.; Giglione, C.; Blanc, V.; Dupuy, A.; Chevrier, M.; Gil, P.; Famechon, A.; Meinnel, T.; Mikol, V. The crystal structures of four peptide deformylases bound to the antibiotic actinonin reveal two distinct types: a platform for the structure-based design of antibacterial agents. J. Mol. Biol., 2002, 320(5), 951-962.
[http://dx.doi.org/10.1016/S0022-2836(02)00549-1] [PMID: 12126617]
[6]
Boularot, A.; Giglione, C.; Artaud, I.; Meinnel, T. Structure-activity relationship analysis and therapeutic potential of peptide deformylase inhibitors. Curr. Opin. Investig. Drugs, 2004, 5(8), 809-822.
[PMID: 15600237]
[7]
BioSolvelt GmbH, An der Ziegelei 75, D-53757 Sankt Augustin, Germanyhttp://www.biosolveit.de/FlexX/
[8]
Merzoug, A.; Chikhi, A.; Bensegueni, A.; Boucherit, H.; Okay, S. Virtual screening approach of bacterial peptide deformylase inhibitors results in new antibiotics. Mol. Inform., 2018, 37(3)1700087
[http://dx.doi.org/10.1002/minf.201700087] [PMID: 28991412]
[9]
Apfel, C.; Banner, D.W.; Bur, D.; Dietz, M.; Hubschwerlen, C.; Locher, H.; Marlin, F.; Masciadri, R.; Pirson, W.; Stalder, H. 2-(2-Oxo-1,4-dihydro-2H-quinazolin-3-yl)- and 2-(2,2-dioxo-1,4-dihydro-2H-2λ6-benzo[1,2,6]thiadiazin-3-yl)-N-hydroxy-acetamides as potent and selective peptide deformylase inhibitors. J. Med. Chem., 2001, 44(12), 1847-1852.
[http://dx.doi.org/10.1021/jm000352g] [PMID: 11384231]
[10]
Howard, M.H.; Cenizal, T.; Gutteridge, S.; Hanna, W.S.; Tao, Y.; Totrov, M.; Wittenbach, V.A.; Zheng, Y.J. A novel class of inhibitors of peptide deformylase discovered through high-throughput screening and virtual ligand screening. J. Med. Chem., 2004, 47(27), 6669-6672.
[http://dx.doi.org/10.1021/jm049222o] [PMID: 15615515]
[11]
Jayasekera, M.M.K.; Kendall, A.; Shammas, R.; Dermyer, M.; Tomala, M.; Shapiro, M.A.; Holler, T.P. Novel nonpeptidic inhibitors of peptide deformylase. Arch. Biochem. Biophys., 2000, 381(2), 313-316.
[http://dx.doi.org/10.1006/abbi.2000.1987] [PMID: 11032420]
[12]
Meinnel, T.; Patiny, L.; Ragusa, S.; Blanquet, S. Design and synthesis of substrate analogue inhibitors of peptide deformylase. Biochemistry, 1999, 38(14), 4287-4295.
[http://dx.doi.org/10.1021/bi982622r] [PMID: 10194346]
[13]
Chen, D.Z.; Patel, D.V.; Hackbarth, C.J.; Wang, W.; Dreyer, G.; Young, D.C.; Margolis, P.S.; Wu, C.; Ni, Z.J.; Trias, J.; White, R.J.; Yuan, Z. Actinonin, a naturally occurring antibacterial agent, is a potent deformylase inhibitor. Biochemistry, 2000, 39(6), 1256-1262.
[http://dx.doi.org/10.1021/bi992245y] [PMID: 10684604]
[14]
Jones, R.N.; Fritsche, T.R.; Sader, H.S. Antimicrobial spectrum and activity of NVP PDF-713, a novel peptide deformylase inhibitor, tested against 1,837 recent Gram-positive clinical isolates. Diagn. Microbiol. Infect. Dis., 2004, 49(1), 63-65.
[http://dx.doi.org/10.1016/j.diagmicrobio.2003.12.005] [PMID: 15135503]
[15]
Jones, R.N.; Sader, H.S.; Fritsche, T.R. Antimicrobial activity of LBM415 (NVP PDF-713) tested against pathogenic Neisseria spp. (Neisseria gonorrhoeae and Neisseria meningitidis). Diagn. Microbiol. Infect. Dis., 2005, 51(2), 139-141.
[http://dx.doi.org/10.1016/j.diagmicrobio.2004.08.016] [PMID: 15698721]
[16]
Chae, P.S.; Kim, M.S.; Jeung, C.S.; Lee, S.D.; Park, H.; Lee, S.; Suh, J. Peptide-cleaving catalyst selective for peptide deformylase. J. Am. Chem. Soc., 2005, 127(8), 2396-2397.
[http://dx.doi.org/10.1021/ja044043h] [PMID: 15724986]
[17]
Boularot, A.; Giglione, C.; Petit, S.; Duroc, Y.; Alves de Sousa, R.; Larue, V.; Cresteil, T.; Dardel, F.; Artaud, I.; Meinnel, T. Discovery and refinement of a new structural class of potent peptide deformylase inhibitors. J. Med. Chem., 2007, 50(1), 10-20.
[http://dx.doi.org/10.1021/jm060910c] [PMID: 17201406]
[18]
Rarey, M.; Kramer, B.; Lengauer, T.; Klebe, G. A fast flexible docking method using an incremental construction algorithm. J. Mol. Biol., 1996, 261(3), 470-489.
[http://dx.doi.org/10.1006/jmbi.1996.0477] [PMID: 8780787]
[19]
Kramer, B.; Rarey, M.; Lengauer, T. Evaluation of the FLEXX incremental construction algorithm for protein-ligand docking. Proteins, 1999, 37(2), 228-241.
[http://dx.doi.org/10.1002/(SICI)1097-0134(19991101)37:2<228:AID-PROT8>3.0.CO;2-8] [PMID: 10584068]
[20]
Gohlke, H.; Klebe, G. Approaches to the description and prediction of the binding affinity of small-molecule ligands to macromolecular receptors. Angew. Chem. Int. Ed. Engl., 2002, 41(15), 2644-2676.
[http://dx.doi.org/10.1002/1521-3773(20020802)41:15<2644:AID-ANIE2644>3.0.CO;2-O] [PMID: 12203463]
[21]
Kim, E.E.; Kim, K.H.; Moon, J.H.; Choi, K.; Lee, H.K.; Park, H.S. Structures of actinonin bound peptide deformylases from E. faecalis and S. pyogenes. 2008http://www.rcsb.org/pdb/explore/explore.do?structureId=2OS1 (Accessed 17 June 2014).
[22]
Moellering, R.C. Jr Discovering new antimicrobial agents. Int. J. Antimicrob. Agents, 2011, 37(1), 2-9.
[http://dx.doi.org/10.1016/j.ijantimicag.2010.08.018] [PMID: 21075608]
[23]
Sanjay, K.V.; Jat, R.K.; Narendra, N.; Rajkumar, S.; Vineet, S.; Sanjay, P.; Kuldeep, B. novel antibacterial target: peptide deformylase. Pharmacophore., 2011, 2, 114-123.
[24]
Butler, D.; Chen, D.; O’Dwyer, K.; Lewandowski, T.; Aubart, K.; Zalacain, M. Potent sub-MIC effect of GSK1322322 and other peptide deformylase inhibitors on in vitro growth of Staphylococcus aureus. Antimicrob. Agents Chemother., 2014, 58(1), 290-296.
[http://dx.doi.org/10.1128/AAC.01292-13] [PMID: 24165188]
[25]
Standardisation de l’antibiogramme à l’échelle nationale (médecine humaine et vétérinaire) 6ème édition 2011.http://2, www.sante.dz/aarn (Accessed on: June 15, 2016)
[26]
Warren, G.L.; Andrews, C.W.; Capelli, A.M.; Clarke, B.; LaLonde, J.; Lambert, M.H.; Lindvall, M.; Nevins, N.; Semus, S.F.; Senger, S.; Tedesco, G.; Wall, I.D.; Woolven, J.M.; Peishoff, C.E.; Head, M.S. A critical assessment of docking programs and scoring functions. J. Med. Chem., 2006, 49(20), 5912-5931.
[http://dx.doi.org/10.1021/jm050362n] [PMID: 17004707]
[27]
Islam, M.A.; Pillay, T.S. Exploration of the structural requirements of HIV-protease inhibitors using pharmacophore, virtual screening and molecular docking approaches for lead identification. J. Mol. Graph. Model., 2015, 56, 20-30.
[http://dx.doi.org/10.1016/j.jmgm.2014.11.015] [PMID: 25541527]
[28]
Sarangi, A.N.; Lohani, M.; Aggarwal, R. Proteome mining for drug target identification in Listeria monocytogenes strain EGD-e and structure-based virtual screening of a candidate drug target penicillin binding protein 4. J. Microbiol. Methods, 2015, 111, 9-18.
[http://dx.doi.org/10.1016/j.mimet.2015.01.011] [PMID: 25601791]


Rights & PermissionsPrintExport Cite as


Article Details

VOLUME: 15
ISSUE: 2
Year: 2019
Page: [120 - 132]
Pages: 13
DOI: 10.2174/1573408015666190621095916

Article Metrics

PDF: 7