Pharmaceutical Approaches to Target Antibiotic Resistance Mechanisms

Journal of Medicinal Chemistry

Volumn 60, Issue 20, 2017, Pages 8268-8297

  Schillaci, Domenico ^a   Spanò, Virginia ^a   Parrino, Barbara ^a   Carbone, Anna ^a   Montalbano, Alessandra ^a   Barraja, Paola ^a   Diana, Patrizia ^a   Cirrincione, Girolamo ^a   Cascioferro, Stella ^a  

^a UNIVERSITY OF PALERMO   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

2 PHENYLHYDRAZINYLIDENE DERIVATIVE; AMINOGLYCOSIDE; ANTIBIOTIC AGENT; AVIBACTAM; BETA LACTAMASE; BETA LACTAMASE INHIBITOR; BORONIC ACID DERIVATIVE; CARBAZOLE DERIVATIVE; CHALCONE DERIVATIVE; CHEMICAL AGENT; DICARBOXYLIC ACID; EFFLUX PUMP INHIBITOR; HETEROCYCLIC COMPOUND; IMIDAZOLE DERIVATIVE; IMIPENEM; INDOLE DERIVATIVE; NAPHTHENE COMPOUND; PEPTIDOMIMETIC AGENT; PIPERAZINE DERIVATIVE; PYRAZOLE DERIVATIVE; PYRROXAMYCIN; QUINOLINE DERIVATIVE; QUINOLONE DERIVATIVE; RELEBACTAM; SULFONAMIDE; UNCLASSIFIED DRUG; AZABICYCLO DERIVATIVE; MK-7655;

ANTIBIOTIC RESISTANCE; ANTIBIOTIC THERAPY; CARBAPENEM RESISTANT ENTEROBACTERIACEAE; CHEMICAL STRUCTURE; DRUG STRUCTURE; ENTEROBACTERIACEAE INFECTION; GRAM NEGATIVE BACTERIUM; MINIMUM INHIBITORY CONCENTRATION; PSEUDOMONAS INFECTION; REVIEW; DRUG EFFECTS; HUMAN;

AZABICYCLO COMPOUNDS; BETA-LACTAMASE INHIBITORS; DRUG RESISTANCE, MICROBIAL; ENTEROBACTERIACEAE INFECTIONS; HUMANS; IMIPENEM; PSEUDOMONAS INFECTIONS;

EID: 85032443043     PISSN: 00222623     EISSN: 15204804     Source Type: Journal    
DOI: 10.1021/acs.jmedchem.7b00215     Document Type: Review

References (173)

1. Ventola, C. L. The Antibiotic Resistance Crisis Pharm. Ther. 2015, 40 (4) 277-283
2. Roberts, R. R.; Hota, B.; Ahmad, I.; Scott, R. D., II; Foster, S. D.; Abbasi, F.; Schabowski, S.; Kampe, L. M.; Ciavarella, G. G.; Supino, M.; Naples, J.; Cordell, R.; Levy, S. B.; Weinstein, R. A. Hospital and Societal Costs of Antimicrobial-Resistant Infections in a Chicago Teaching Hospital: Implications for Antibiotic Stewardship Clin. Infect. Dis. 2009, 49 (8) 1175-1184 10.1086/605630
3. Pendleton, J. N.; Gorman, S. P.; Gilmore, B. F. Clinical Relevance of the ESKAPE Pathogens Expert Rev. Anti-Infect. Ther. 2013, 11 (3) 297-308 10.1586/eri.13.12
4. Høiby, N.; Bjarnsholt, T.; Givskov, M.; Molin, S.; Ciofu, O. Antibiotic Resistance of Bacterial Biofilms Int. J. Antimicrob. Agents 2010, 35 (4) 322-332 10.1016/j.ijantimicag.2009.12.011
5. Cascioferro, S.; Totsika, M.; Schillaci, D. Sortase A: An Ideal Target for Anti-Virulence Drug Development Microb. Pathog. 2014, 77, 105-112 10.1016/j.micpath.2014.10.007
6. Cascioferro, S.; Raffa, D.; Maggio, B.; Raimondi, M. V.; Schillaci, D.; Daidone, G. Sortase A Inhibitors: Recent Advances and Future Perspectives J. Med. Chem. 2015, 58 (23) 9108-9123 10.1021/acs.jmedchem.5b00779
7. Cascioferro, S.; Cusimano, M. G.; Schillaci, D. Antiadhesion Agents against Gram-Positive Pathogens Future Microbiol. 2014, 9, 1209-1220 10.2217/fmb.14.56
8. Penesyan, A.; Gillings, M.; Paulsen, I. T. Antibiotic Discovery: Combatting Bacterial Resistance in Cells and in Biofilm Communities Molecules 2015, 20 (4) 5286-5298 10.3390/molecules20045286
9. Sánchez-Romero, M. A.; Casadesús, J. Contribution of Phenotypic Heterogeneity to Adaptive Antibiotic Resistance Proc. Natl. Acad. Sci. U. S. A. 2014, 111 (1) 355-360 10.1073/pnas.1316084111
10. Schillaci, D.; Petruso, S.; Raimondi, M. V.; Cusimano, M. G.; Cascioferro, S.; Scalisi, M.; La Giglia, M. A.; Vitale, M. Pyrrolomycins as Potential Anti-Staphylococcal Biofilms Agents Biofouling 2010, 26 (4) 433-438 10.1080/08927011003718673
11. Ambler, R. P.; Coulson, A. F.; Frère, J. M.; Ghuysen, J. M.; Joris, B.; Forsman, M.; Levesque, R. C.; Tiraby, G.; Waley, S. G. A Standard Numbering Scheme for the Class A Beta-Lactamases Biochem. J. 1991, 276, 269-270 10.1042/bj2760269
12. Bush, K.; Jacoby, G. A. Updated Functional Classification of β-Lactamases Antimicrob. Agents Chemother. 2010, 54 (3) 969-976 10.1128/AAC.01009-09
13. Yigit, H.; Queenan, A. M.; Rasheed, J. K.; Biddle, J. W.; Domenech-Sanchez, A.; Alberti, S.; Bush, K.; Tenover, F. C. Carbapenem-Resistant Strain of Klebsiella Oxytoca Harboring Carbapenem-Hydrolyzingβ -Lactamase KPC-2 Antimicrob. Agents Chemother. 2003, 47 (12) 3881-3889 10.1128/AAC.47.12.3881-3889.2003
14. Bonomo, R. A. New Delhi Metallo-β-Lactamase and Multidrug Resistance: A Global SOS? Clin. Infect. Dis. 2011, 52 (4) 485-487 10.1093/cid/ciq179
15. Khan, A.; Faheem, M.; Danishuddin, M.; Khan, A. U. Evaluation of Inhibitory Action of Novel Non β-Lactam Inhibitor against Klebsiella Pneumoniae Carbapenemase (KPC-2) PLoS One 2014, 9 (9) e108246 10.1371/journal.pone.0108246
16. Bratu, S.; Mooty, M.; Nichani, S.; Landman, D.; Gullans, C.; Pettinato, B.; Karumudi, U.; Tolaney, P.; Quale, J. Emergence of KPC-Possessing Klebsiella Pneumoniae in Brooklyn, New York: Epidemiology and Recommendations for Detection Antimicrob. Agents Chemother. 2005, 49 (7) 3018-3020 10.1128/AAC.49.7.3018-3020.2005
17. Bush, K. A Resurgence of β-Lactamase Inhibitor Combinations Effective against Multidrug-Resistant Gram-Negative Pathogens Int. J. Antimicrob. Agents 2015, 46 (5) 483-493 10.1016/j.ijantimicag.2015.08.011
18. Zhanel, G. G.; Lawson, C. D.; Adam, H.; Schweizer, F.; Zelenitsky, S.; Lagacé-Wiens, P. R. S.; Denisuik, A.; Rubinstein, E.; Gin, A. S.; Hoban, D. J.; Lynch, J. P.; Karlowsky, J. A. Ceftazidime-Avibactam: A Novel Cephalosporin/β-Lactamase Inhibitor Combination Drugs 2013, 73 (2) 159-177 10.1007/s40265-013-0013-7
19. Gardiner, B. J.; Golan, Y. Ceftazidime-Avibactam (CTZ-AVI) as a Treatment for Hospitalized Adult Patients with Complicated Intra-Abdominal Infections Expert Rev. Anti-Infect. Ther. 2016, 14 (5) 451-463 10.1586/14787210.2016.1173542
20. Vasoo, S.; Cunningham, S. A.; Cole, N. C.; Kohner, P. C.; Menon, S. R.; Krause, K. M.; Harris, K. A.; De, P. P.; Koh, T. H.; Patel, R. In Vitro Activities of Ceftazidime-Avibactam, Aztreonam-Avibactam, and a Panel of Older and Contemporary Antimicrobial Agents against Carbapenemase-Producing Gram-Negative Bacilli Antimicrob. Agents Chemother. 2015, 59 (12) 7842-7846 10.1128/AAC.02019-15
21. Bhalodi, A. A.; Crandon, J. L.; Williams, G.; Nicolau, D. P. In Vivo Efficacy of Humanized Ceftaroline Fosamil-Avibactam Exposures in a Polymicrobial Infection Model Antimicrob. Agents Chemother. 2013, 57 (11) 5674-5678 10.1128/AAC.01162-13
22. Li, H.; Estabrook, M.; Jacoby, G. A.; Nichols, W. W.; Testa, R. T.; Bush, K. In Vitro Susceptibility of Characterized β-Lactamase-Producing Strains Tested with Avibactam Combinations Antimicrob. Agents Chemother. 2015, 59 (3) 1789-1793 10.1128/AAC.04191-14
23. Lagacé-Wiens, P.; Walkty, A.; Karlowsky, J. A. Ceftazidime-Avibactam: An Evidence-Based Review of Its Pharmacology and Potential Use in the Treatment of Gram-Negative Bacterial Infections Core Evid. 2014, 9, 13-25 10.2147/CE.S40698
24. Ehmann, D. E.; Jahić, H.; Ross, P. L.; Gu, R.-F.; Hu, J.; Kern, G.; Walkup, G. K.; Fisher, S. L. Avibactam Is a Covalent, Reversible, Non-β-Lactam β-Lactamase Inhibitor Proc. Natl. Acad. Sci. U. S. A. 2012, 109 (29) 11663-11668 10.1073/pnas.1205073109
25. Asli, A.; Brouillette, E.; Krause, K. M.; Nichols, W. W.; Malouin, F. Distinctive Binding of Avibactam to Penicillin-Binding Proteins of Gram-Negative and Gram-Positive Bacteria Antimicrob. Agents Chemother. 2016, 60 (2) 752-756 10.1128/AAC.02102-15
26. Citron, D. M.; Tyrrell, K. L.; Merriam, V.; Goldstein, E. J. C. In Vitro Activity of Ceftazidime-NXL104 against 396 Strains of β-Lactamase-Producing Anaerobes Antimicrob. Agents Chemother. 2011, 55 (7) 3616-3620 10.1128/AAC.01682-10
27. Sharma, R.; Park, T. E.; Moy, S. Ceftazidime-Avibactam: A Novel Cephalosporin/β-Lactamase Inhibitor Combination for the Treatment of Resistant Gram-Negative Organisms Clin. Ther. 2016, 38, 431-444 10.1016/j.clinthera.2016.01.018
28. Maiti, S. N.; Nguyen, D.; Khan, J.; Ling, R. Bicyclic Compounds and Their Use as Antibacterial Agents and Beta-Lactamase Inhibitors. US 20130225554 A1, 2013.
29. King, A. M.; King, D. T.; French, S.; Brouillette, E.; Asli, A.; Alexander, J. A. N.; Vuckovic, M.; Maiti, S. N.; Parr, T. R.; Brown, E. D.; Malouin, F.; Strynadka, N. C. J.; Wright, G. D. Structural and Kinetic Characterization of Diazabicyclooctanes as Dual Inhibitors of Both Serine-β-Lactamases and Penicillin-Binding Proteins ACS Chem. Biol. 2016, 11 (4) 864-868 10.1021/acschembio.5b00944
30. Karlowsky, J. A.; Biedenbach, D. J.; Kazmierczak, K. M.; Stone, G. G.; Sahm, D. F. The Activity of Ceftazidime-Avibactam against Extended-Spectrum and AmpC β-Lactamase-Producing Enterobacteriaceae Collected in the INFORM Global Surveillance Study in 2012-2014 Antimicrob. Agents Chemother. 2016, 60 (5) 2849-2857 10.1128/AAC.02286-15
31. Mangion, I. K.; Ruck, R. T.; Rivera, N.; Huffman, M. A.; Shevlin, M. A Concise Synthesis of a β-Lactamase Inhibitor Org. Lett. 2011, 13 (20) 5480-5483 10.1021/ol202195n
32. Hirsch, E. B.; Ledesma, K. R.; Chang, K.-T.; Schwartz, M. S.; Motyl, M. R.; Tam, V. H. In Vitro Activity of MK-7655, a Novel β-Lactamase Inhibitor, in Combination with Imipenem against Carbapenem-Resistant Gram-Negative Bacteria Antimicrob. Agents Chemother. 2012, 56 (7) 3753-3757 10.1128/AAC.05927-11
33. Dobozy, O.; Mile, I.; Ferencz, I.; Csányi, V. Effect of Electrolytes on the Activity and Iodine Sensitivity of Penicillinase from B. Cereus Acta Biochim. Biophys. Acad. Sci. Hung. 1971, 6 (2) 97-105
34. Morandi, F.; Caselli, E.; Morandi, S.; Focia, P. J.; Blázquez, J.; Shoichet, B. K.; Prati, F. Nanomolar Inhibitors of AmpC Beta-Lactamase J. Am. Chem. Soc. 2003, 125 (3) 685-695 10.1021/ja0288338
35. Tondi, D.; Venturelli, A.; Bonnet, R.; Pozzi, C.; Shoichet, B. K.; Costi, M. P. Targeting Class A and C Serine β-Lactamases with a Broad-Spectrum Boronic Acid Derivative J. Med. Chem. 2014, 57 (12) 5449-5458 10.1021/jm5006572
36. Powers, R. A.; Blázquez, J.; Weston, G. S.; Morosini, M. I.; Baquero, F.; Shoichet, B. K. The Complexed Structure and Antimicrobial Activity of a Non-Beta-Lactam Inhibitor of AmpC Beta-Lactamase Protein Sci. Publ. Protein Soc. 1999, 8 (11) 2330-2337 10.1110/ps.8.11.2330
37. Wang, X.; Minasov, G.; Blázquez, J.; Caselli, E.; Prati, F.; Shoichet, B. K. Recognition and Resistance in TEM β-Lactamase Biochemistry 2003, 42 (28) 8434-8444 10.1021/bi034242y
38. Chen, Y.; Delmas, J.; Sirot, J.; Shoichet, B.; Bonnet, R. Atomic Resolution Structures of CTX-M Beta-Lactamases: Extended Spectrum Activities from Increased Mobility and Decreased Stability J. Mol. Biol. 2005, 348 (2) 349-362 10.1016/j.jmb.2005.02.010
39. Burns, C. J.; Jackson, R. W.; Goswami, R.; Xu, H. Beta-Lactamase Inhibitors. WO 2009064414, 2009.
40. Hecker, S. J.; Reddy, K. R.; Totrov, M.; Hirst, G. C.; Lomovskaya, O.; Griffith, D. C.; King, P.; Tsivkovski, R.; Sun, D.; Sabet, M.; Tarazi, Z.; Clifton, M. C.; Atkins, K.; Raymond, A.; Potts, K. T.; Abendroth, J.; Boyer, S. H.; Loutit, J. S.; Morgan, E. E.; Durso, S.; Dudley, M. N. Discovery of a Cyclic Boronic Acid β-Lactamase Inhibitor (RPX7009) with Utility vs Class A Serine Carbapenemases J. Med. Chem. 2015, 58 (9) 3682-3692 10.1021/acs.jmedchem.5b00127
41. Goldstein, E. J. C.; Citron, D. M.; Tyrrell, K. L.; Merriam, C. V. In Vitro Activity of Biapenem plus RPX7009, a Carbapenem Combined with a Serine β-Lactamase Inhibitor, against Anaerobic Bacteria Antimicrob. Agents Chemother. 2013, 57 (6) 2620-2630 10.1128/AAC.02418-12
42. Lapuebla, A.; Abdallah, M.; Olafisoye, O.; Cortes, C.; Urban, C.; Quale, J.; Landman, D. Activity of Meropenem Combined with RPX7009, a Novel β-Lactamase Inhibitor, against Gram-Negative Clinical Isolates in New York City Antimicrob. Agents Chemother. 2015, 59 (8) 4856-4860 10.1128/AAC.00843-15
43. Tan, Q.; Ogawa, A. M.; Painter, R. E.; Park, Y.-W.; Young, K.; DiNinno, F. P. 4,7-Dichloro Benzothien-2-Yl Sulfonylaminomethyl Boronic Acid: First Boronic Acid-Derived Beta-Lactamase Inhibitor with Class A, C, and D Activity Bioorg. Med. Chem. Lett. 2010, 20 (8) 2622-2624 10.1016/j.bmcl.2010.02.065
44. Eidam, O.; Romagnoli, C.; Caselli, E.; Babaoglu, K.; Pohlhaus, D. T.; Karpiak, J.; Bonnet, R.; Shoichet, B. K.; Prati, F. Design, Synthesis, Crystal Structures, and Antimicrobial Activity of Sulfonamide Boronic Acids as β-Lactamase Inhibitors J. Med. Chem. 2010, 53 (21) 7852-7863 10.1021/jm101015z
45. Tondi, D.; Calò, S.; Shoichet, B. K.; Costi, M. P. Structural Study of Phenyl Boronic Acid Derivatives as AmpC β-Lactamase Inhibitors Bioorg. Med. Chem. Lett. 2010, 20 (11) 3416-3419 10.1016/j.bmcl.2010.04.007
46. Eidam, O.; Romagnoli, C.; Dalmasso, G.; Barelier, S.; Caselli, E.; Bonnet, R.; Shoichet, B. K.; Prati, F. Fragment-Guided Design of Subnanomolar β-Lactamase Inhibitors Active in Vivo Proc. Natl. Acad. Sci. U. S. A. 2012, 109 (43) 17448-17453 10.1073/pnas.1208337109
47. Rojas, L. J.; Taracila, M. A.; Papp-Wallace, K. M.; Bethel, C. R.; Caselli, E.; Romagnoli, C.; Winkler, M. L.; Spellberg, B.; Prati, F.; Bonomo, R. A. Boronic Acid Transition State Inhibitors Active against KPC and Other Class A β-Lactamases: Structure-Activity Relationships as a Guide to Inhibitor Design Antimicrob. Agents Chemother. 2016, 60 (3) 1751-1759 10.1128/AAC.02641-15
48. Nguyen, N. Q.; Krishnan, N. P.; Rojas, L. J.; Prati, F.; Caselli, E.; Romagnoli, C.; Bonomo, R. A.; van den Akker, F. Crystal Structures of KPC-2 and SHV-1 β-Lactamases in Complex with the Boronic Acid Transition State Analog S02030 Antimicrob. Agents Chemother. 2016, 60 (3) 1760-1766 10.1128/AAC.02643-15
49. Krishnan, N. P.; Nguyen, N. Q.; Papp-Wallace, K. M.; Bonomo, R. A.; van den Akker, F. van den. Inhibition of Klebsiella β-Lactamases (SHV-1 and KPC-2) by Avibactam: A Structural Study PLoS One 2015, 10 (9) e0136813 10.1371/journal.pone.0136813
50. Danishuddin, M.; Khan, A.; Faheem, M.; Kalaiarasan, P.; Hassan Baig, M.; Subbarao, N.; Khan, A. U. Structure-Based Screening of Inhibitors against KPC-2: Designing Potential Drug Candidates against Multidrug-Resistant Bacteria J. Biomol. Struct. Dyn. 2014, 32 (5) 741-750 10.1080/07391102.2013.789988
51. Toney, J. H.; Hammond, G. G.; Fitzgerald, P. M.; Sharma, N.; Balkovec, J. M.; Rouen, G. P.; Olson, S. H.; Hammond, M. L.; Greenlee, M. L.; Gao, Y. D. Succinic Acids as Potent Inhibitors of Plasmid-Borne IMP-1 Metallo-Beta-Lactamase J. Biol. Chem. 2001, 276 (34) 31913-31918 10.1074/jbc.M104742200
52. Hiraiwa, Y.; Morinaka, A.; Fukushima, T.; Kudo, T. Metallo-Beta-Lactamase Inhibitory Activity of Phthalic Acid Derivatives Bioorg. Med. Chem. Lett. 2009, 19 (17) 5162-5165 10.1016/j.bmcl.2009.07.018
53. Feng, L.; Yang, K.-W.; Zhou, L.-S.; Xiao, J.-M.; Yang, X.; Zhai, L.; Zhang, Y.-L.; Crowder, M. W. N-Heterocyclic Dicarboxylic Acids: Broad-Spectrum Inhibitors of Metallo-β-Lactamases with Co-Antibacterial Effect against Antibiotic-Resistant Bacteria Bioorg. Med. Chem. Lett. 2012, 22 (16) 5185-5189 10.1016/j.bmcl.2012.06.074
54. Garau, G.; García-Sáez, I.; Bebrone, C.; Anne, C.; Mercuri, P.; Galleni, M.; Frère, J.-M.; Dideberg, O. Update of the Standard Numbering Scheme for Class B β-Lactamases Antimicrob. Agents Chemother. 2004, 48 (7) 2347-2349 10.1128/AAC.48.7.2347-2349.2004
55. Hiraiwa, Y.; Morinaka, A.; Fukushima, T.; Kudo, T. Metallo-β-Lactamase Inhibitory Activity of 3-Alkyloxy and 3-Amino Phthalic Acid Derivatives and Their Combination Effect with Carbapenem Bioorg. Med. Chem. 2013, 21 (18) 5841-5850 10.1016/j.bmc.2013.07.006
56. Hiraiwa, Y.; Saito, J.; Watanabe, T.; Yamada, M.; Morinaka, A.; Fukushima, T.; Kudo, T. X-Ray Crystallographic Analysis of IMP-1 Metallo-β-Lactamase Complexed with a 3-Aminophthalic Acid Derivative, Structure-Based Drug Design, and Synthesis of 3,6-Disubstituted Phthalic Acid Derivative Inhibitors Bioorg. Med. Chem. Lett. 2014, 24 (20) 4891-4894 10.1016/j.bmcl.2014.08.039
57. Zhang, Y.-L.; Yang, K.-W.; Zhou, Y.-J.; LaCuran, A. E.; Oelschlaeger, P.; Crowder, M. W. Diaryl-Substituted Azolylthioacetamides: Inhibitor Discovery of New Delhi Metallo-β-Lactamase-1 (NDM-1) ChemMedChem 2014, 9 (11) 2445-2448 10.1002/cmdc.201402249
58. Christopeit, T.; Yang, K.-W.; Yang, S.-K.; Leiros, H.-K. S. The Structure of the Metallo-β-Lactamase VIM-2 in Complex with a Triazolylthioacetamide Inhibitor Acta Crystallogr., Sect. F: Struct. Biol. Commun. 2016, 72 (11) 813-819 10.1107/S2053230X16016113
59. Arjomandi, O. K.; Hussein, W. M.; Vella, P.; Yusof, Y.; Sidjabat, H. E.; Schenk, G.; McGeary, R. P. Design, Synthesis, and in Vitro and Biological Evaluation of Potent Amino Acid-Derived Thiol Inhibitors of the Metallo-β-Lactamase IMP-1 Eur. J. Med. Chem. 2016, 114, 318-327 10.1016/j.ejmech.2016.03.017
60. Yusof, Y.; Tan, D. T. C.; Arjomandi, O. K.; Schenk, G.; McGeary, R. P. Captopril Analogues as Metallo-β-Lactamase Inhibitors Bioorg. Med. Chem. Lett. 2016, 26 (6) 1589-1593 10.1016/j.bmcl.2016.02.007
61. Li, N.; Xu, Y.; Xia, Q.; Bai, C.; Wang, T.; Wang, L.; He, D.; Xie, N.; Li, L.; Wang, J.; Zhou, H.-G.; Xu, F.; Yang, C.; Zhang, Q.; Yin, Z.; Guo, Y.; Chen, Y. Simplified Captopril Analogues as NDM-1 Inhibitors Bioorg. Med. Chem. Lett. 2014, 24 (1) 386-389 10.1016/j.bmcl.2013.10.068
62. Hussein, W. M.; Fatahala, S. S.; Mohamed, Z. M.; McGeary, R. P.; Schenk, G.; Ollis, D. L.; Mohamed, M. S. Synthesis and Kinetic Testing of Tetrahydropyrimidine-2-Thione and Pyrrole Derivatives as Inhibitors of the Metallo-β-Lactamase from Klebsiella Pneumonia and Pseudomonas Aeruginosa Chem. Biol. Drug Des. 2012, 80 (4) 500-515 10.1111/j.1747-0285.2012.01440.x
63. Brown, D. Antibiotic Resistance Breakers: Can Repurposed Drugs Fill the Antibiotic Discovery Void? Nat. Rev. Drug Discovery 2015, 14 (12) 821-832 10.1038/nrd4675
64. Nauton, L.; Kahn, R.; Garau, G.; Hernandez, J. F.; Dideberg, O. Structural Insights into the Design of Inhibitors for the L1Metallo-Beta-Lactamase from Stenotrophomonas Maltophilia J. Mol. Biol. 2008, 375 (1) 257-269 10.1016/j.jmb.2007.10.036
65. Liénard, B. M. R.; Garau, G.; Horsfall, L.; Karsisiotis, A. I.; Damblon, C.; Lassaux, P.; Papamicael, C.; Roberts, G. C. K.; Galleni, M.; Dideberg, O.; Frère, J.-M.; Schofield, C. J. Structural Basis for the Broad-Spectrum Inhibition of Metallo-β-Lactamases by Thiols Org. Biomol. Chem. 2008, 6 (13) 2282-2294 10.1039/b802311e
66. Vella, P.; Hussein, W. M.; Leung, E. W. W.; Clayton, D.; Ollis, D. L.; Mitić, N.; Schenk, G.; McGeary, R. P. The Identification of New Metallo-β-Lactamase Inhibitor Leads from Fragment-Based Screening Bioorg. Med. Chem. Lett. 2011, 21 (11) 3282-3285 10.1016/j.bmcl.2011.04.027
67. Faridoon; Hussein, W. M.; Vella, P.; Islam, N. U.; Ollis, D. L.; Schenk, G.; McGeary, R. P. 3-Mercapto-1,2,4-Triazoles and N-Acylated Thiosemicarbazides as Metallo-β-Lactamase Inhibitors Bioorg. Med. Chem. Lett. 2012, 22 (1) 380-386 10.1016/j.bmcl.2011.10.116
68. Carosso, S.; Miller, M. J. Syntheses and Studies of New Forms of N-Sulfonyloxy β-Lactams as Potential Antibacterial Agents and β-Lactamase Inhibitors Bioorg. Med. Chem. 2015, 23 (18) 6138-6147 10.1016/j.bmc.2015.08.005
69. Papp-Wallace, K. M.; Bethel, C. R.; Gootz, T. D.; Shang, W.; Stroh, J.; Lau, W.; McLeod, D.; Price, L.; Marfat, A.; Distler, A.; Drawz, S. M.; Chen, H.; Harry, E.; Nottingham, M.; Carey, P. R.; Buynak, J. D.; Bonomo, R. A. Inactivation of a Class A and a Class C β-Lactamase by 6β-(Hydroxymethyl)penicillanic Acid Sulfone Biochem. Pharmacol. 2012, 83 (4) 462-471 10.1016/j.bcp.2011.11.015
70. Lella, R. K.; Sharma, C. Eis (Enhanced Intracellular Survival) Protein of Mycobacterium Tuberculosis Disturbs the Cross Regulation of T-Cells J. Biol. Chem. 2007, 282 (26) 18671-18675 10.1074/jbc.C600280200
71. Garneau-Tsodikova, S.; Labby, K. J. Mechanisms of Resistance to Aminoglycoside Antibiotics: Overview and Perspectives MedChemComm 2016, 7 (1) 11-27 10.1039/C5MD00344J
72. Lin, D. L.; Tran, T.; Alam, J. Y.; Herron, S. R.; Ramirez, M. S.; Tolmasky, M. E. Inhibition of Aminoglycoside 6′-N-Acetyltransferase Type Ib by Zinc: Reversal of Amikacin Resistance in Acinetobacter Baumannii and Escherichia Coli by a Zinc Ionophore Antimicrob. Agents Chemother. 2014, 58 (7) 4238-4241 10.1128/AAC.00129-14
73. Li, Y.; Green, K. D.; Johnson, B. R.; Garneau-Tsodikova, S. Inhibition of Aminoglycoside Acetyltransferase Resistance Enzymes by Metal Salts Antimicrob. Agents Chemother. 2015, 59 (7) 4148-4156 10.1128/AAC.00885-15
74. Gao, F.; Yan, X.; Baettig, O. M.; Berghuis, A. M.; Auclair, K. Regio- and Chemoselective 6′-N-Derivatization of Aminoglycosides: Bisubstrate Inhibitors as Probes to Study Aminoglycoside 6′-N-Acetyltransferases Angew. Chem., Int. Ed. 2005, 44 (42) 6859-6862 10.1002/anie.200501399
75. Lin, D. L.; Tran, T.; Adams, C.; Alam, J. Y.; Herron, S. R.; Tolmasky, M. E. Inhibitors of the Aminoglycoside 6′-N-Acetyltransferase Type Ib [AAC(6′)-Ib] Identified by in Silico Molecular Docking Bioorg. Med. Chem. Lett. 2013, 23 (20) 5694-5698 10.1016/j.bmcl.2013.08.016
76. Vetting, M. W.; Park, C. H.; Hegde, S. S.; Jacoby, G. A.; Hooper, D. C.; Blanchard, J. S. Mechanistic and Structural Analysis of Aminoglycoside N-Acetyltransferase AAC(6′)-Ib and Its Bifunctional, Fluoroquinolone-Active AAC(6′)-Ib-Cr Variant Biochemistry 2008, 47 (37) 9825-9835 10.1021/bi800664x
77. Green, K. D.; Chen, W.; Garneau-Tsodikova, S. Identification and Characterization of Inhibitors of the Aminoglycoside Resistance Acetyltransferase Eis from Mycobacterium Tuberculosis ChemMedChem 2012, 7 (1) 73-77 10.1002/cmdc.201100332
78. Chiem, K.; Jani, S.; Fuentes, B.; Lin, D. L.; Rasche, M. E.; Tolmasky, M. E. Identification of an Inhibitor of the Aminoglycoside 6′-N-Acetyltransferase Type Ib [AAC(6′)-Ib] by Glide Molecular Docking MedChemComm 2016, 7 (1) 184-189 10.1039/C5MD00316D
79. Sun, J.; Deng, Z.; Yan, A. Bacterial Multidrug Efflux Pumps: Mechanisms, Physiology and Pharmacological Exploitations Biochem. Biophys. Res. Commun. 2014, 453 (2) 254-267 10.1016/j.bbrc.2014.05.090
80. Kriengkauykiat, J.; Porter, E.; Lomovskaya, O.; Wong-Beringer, A. Use of an Efflux Pump Inhibitor To Determine the Prevalence of Efflux Pump-Mediated Fluoroquinolone Resistance and Multidrug Resistance in Pseudomonas Aeruginosa Antimicrob. Agents Chemother. 2005, 49 (2) 565-570 10.1128/AAC.49.2.565-570.2005
81. Kvist, M.; Hancock, V.; Klemm, P. Inactivation of Efflux Pumps Abolishes Bacterial Biofilm Formation Appl. Environ. Microbiol. 2008, 74 (23) 7376-7382 10.1128/AEM.01310-08
82. Handzlik, J.; Matys, A.; Kieć-Kononowicz, K. Recent Advances in Multi-Drug Resistance (MDR) Efflux Pump Inhibitors of Gram-Positive Bacteria S. Aureus Antibiotics 2013, 2 (1) 28-45 10.3390/antibiotics2010028
83. Jamshidi, S.; Sutton, J. M.; Rahman, K. M. An Overview of Bacterial Efflux Pumps and Computational Approaches to Study Efflux Pump Inhibitors Future Med. Chem. 2016, 8 (2) 195-210 10.4155/fmc.15.173
84. Mahmood, H. Y.; Jamshidi, S.; Sutton, J. M.; Rahman, K. M. Current Advances in Developing Inhibitors of Bacterial Multidrug Efflux Pumps Curr. Med. Chem. 2016, 23 (10) 1062-1081 10.2174/0929867323666160304150522
85. Werle, M. Natural and Synthetic Polymers as Inhibitors of Drug Efflux Pumps Pharm. Res. 2008, 25 (3) 500-511 10.1007/s11095-007-9347-8
86. Vaara, M. Novel Derivatives of Polymyxins J. Antimicrob. Chemother. 2013, 68 (6) 1213-1219 10.1093/jac/dkt039
87. Brown, P.; Dawson, M. J. Development of New Polymyxin Derivatives for Multi-Drug Resistant Gram-Negative Infections J. Antibiot. 2017, 70 (4) 386-394 10.1038/ja.2016.146
88. Costa, S. S.; Viveiros, M.; Amaral, L.; Couto, I. Multidrug Efflux Pumps in Staphylococcus Aureus: An Update Open Microbiol. J. 2013, 7, 59-71 10.2174/1874285801307010059
89. Pieroni, M.; Dimovska, M.; Brincat, J. P.; Sabatini, S.; Carosati, E.; Massari, S.; Kaatz, G. W.; Fravolini, A. From 6-Aminoquinolone Antibacterials to 6-Amino-7-Thiopyranopyridinylquinolone Ethyl Esters as Inhibitors of Staphylococcus Aureus Multidrug Efflux Pumps J. Med. Chem. 2010, 53 (11) 4466-4480 10.1021/jm1003304
90. Doléans-Jordheim, A.; Veron, J.-B.; Fendrich, O.; Bergeron, E.; Montagut-Romans, A.; Wong, Y.-S.; Furdui, B.; Freney, J.; Dumontet, C.; Boumendjel, A. 3-Aryl-4-Methyl-2-Quinolones Targeting Multiresistant Staphylococcus Aureus Bacteria ChemMedChem 2013, 8 (4) 652-657 10.1002/cmdc.201200551
91. Gibbons, S. Anti-Staphylococcal Plant Natural Products Nat. Prod. Rep. 2004, 21 (2) 263-277 10.1039/b212695h
92. Sabatini, S.; Gosetto, F.; Manfroni, G.; Tabarrini, O.; Kaatz, G. W.; Patel, D.; Cecchetti, V. Evolution from a Natural Flavones Nucleus to Obtain 2-(4-Propoxyphenyl)quinoline Derivatives As Potent Inhibitors of the S. Aureus NorA Efflux Pump J. Med. Chem. 2011, 54 (16) 5722-5736 10.1021/jm200370y
93. Sabatini, S.; Gosetto, F.; Iraci, N.; Barreca, M. L.; Massari, S.; Sancineto, L.; Manfroni, G.; Tabarrini, O.; Dimovska, M.; Kaatz, G. W.; Cecchetti, V. Re-Evolution of the 2-Phenylquinolines: Ligand-Based Design, Synthesis, and Biological Evaluation of a Potent New Class of Staphylococcus Aureus NorA Efflux Pump Inhibitors to Combat Antimicrobial Resistance J. Med. Chem. 2013, 56 (12) 4975-4989 10.1021/jm400262a
94. Sabatini, S.; Kaatz, G. W.; Rossolini, G. M.; Brandini, D.; Fravolini, A. From Phenothiazine to 3-Phenyl-1,4-Benzothiazine Derivatives as Inhibitors of the Staphylococcus Aureus NorA Multidrug Efflux Pump J. Med. Chem. 2008, 51 (14) 4321-4330 10.1021/jm701623q
95. Sabatini, S.; Gosetto, F.; Serritella, S.; Manfroni, G.; Tabarrini, O.; Iraci, N.; Brincat, J. P.; Carosati, E.; Villarini, M.; Kaatz, G. W.; Cecchetti, V. Pyrazolo[4,3-c][1,2]benzothiazines 5,5-Dioxide: A Promising New Class of Staphylococcus Aureus NorA Efflux Pump Inhibitors J. Med. Chem. 2012, 55 (7) 3568-3572 10.1021/jm201446h
96. Brincat, J. P.; Carosati, E.; Sabatini, S.; Manfroni, G.; Fravolini, A.; Raygada, J. L.; Patel, D.; Kaatz, G. W.; Cruciani, G. Discovery of Novel Inhibitors of the NorA Multidrug Transporter of Staphylococcus Aureus J. Med. Chem. 2011, 54 (1) 354-365 10.1021/jm1011963
97. Thota, N.; Reddy, M. V.; Kumar, A.; Khan, I. A.; Sangwan, P. L.; Kalia, N. P.; Koul, J. L.; Koul, S. Substituted Dihydronaphthalenes as Efflux Pump Inhibitors of Staphylococcus Aureus Eur. J. Med. Chem. 2010, 45 (9) 3607-3616 10.1016/j.ejmech.2010.05.006
98. Holler, J. G.; Christensen, S. B.; Slotved, H.-C.; Rasmussen, H. B.; Gúzman, A.; Olsen, C.-E.; Petersen, B.; Mølgaard, P. Novel Inhibitory Activity of the Staphylococcus Aureus NorA Efflux Pump by a Kaempferol Rhamnoside Isolated from Persea Lingue Nees J. Antimicrob. Chemother. 2012, 67 (5) 1138-1144 10.1093/jac/dks005
99. Holler, J. G.; Slotved, H.-C.; Mølgaard, P.; Olsen, C. E.; Christensen, S. B. Chalcone Inhibitors of the NorA Efflux Pump in Staphylococcus Aureus Whole Cells and Enriched Everted Membrane Vesicles Bioorg. Med. Chem. 2012, 20 (14) 4514-4521 10.1016/j.bmc.2012.05.025
100. Fontaine, F.; Hequet, A.; Voisin-Chiret, A.-S.; Bouillon, A.; Lesnard, A.; Cresteil, T.; Jolivalt, C.; Rault, S. First Identification of Boronic Species as Novel Potential Inhibitors of the Staphylococcus Aureus NorA Efflux Pump J. Med. Chem. 2014, 57 (6) 2536-2548 10.1021/jm401808n
101. Fontaine, F.; Héquet, A.; Voisin-Chiret, A.-S.; Bouillon, A.; Lesnard, A.; Cresteil, T.; Jolivalt, C.; Rault, S. Boronic Species as Promising Inhibitors of the Staphylococcus Aureus NorA Efflux Pump: Study of 6-Substituted Pyridine-3-Boronic Acid Derivatives Eur. J. Med. Chem. 2015, 95, 185-198 10.1016/j.ejmech.2015.02.056
102. Burchak, O. N.; Pihive, E. L.; Maigre, L.; Guinchard, X.; Bouhours, P.; Jolivalt, C.; Schneider, D.; Maurin, M.; Giglione, C.; Meinnel, T.; Paris, J.-M.; Denis, J.-N. Synthesis and Evaluation of 1-(1H-Indol-3-Yl)ethanamine Derivatives as New Antibacterial Agents Bioorg. Med. Chem. 2011, 19 (10) 3204-3215 10.1016/j.bmc.2011.03.060
103. Caspar, Y.; Jeanty, M.; Blu, J.; Burchak, O.; Le Pihive, E.; Maigre, L.; Schneider, D.; Jolivalt, C.; Paris, J.-M.; Hequet, A.; Minassian, F.; Denis, J.-N.; Maurin, M. Novel Synthetic Bis-Indolic Derivatives with Antistaphylococcal Activity, Including against MRSA and VISA Strains J. Antimicrob. Chemother. 2015, 70 (6) 1727-1737 10.1093/jac/dkv015
104. German, N.; Kaatz, G. W.; Kerns, R. J. Synthesis and Evaluation of PSSRI-Based Inhibitors of Staphylococcus Aureus Multidrug Efflux Pumps Bioorg. Med. Chem. Lett. 2008, 18 (4) 1368-1373 10.1016/j.bmcl.2008.01.014
105. Fournier dit Chabert, J.; Marquez, B.; Neville, L.; Joucla, L.; Broussous, S.; Bouhours, P.; David, E.; Pellet-Rostaing, S.; Marquet, B.; Moreau, N.; Lemaire, M. Synthesis and Evaluation of New Arylbenzo[b]thiophene and Diarylthiophene Derivatives as Inhibitors of the NorA Multidrug Transporter of Staphylococcus Aureus Bioorg. Med. Chem. 2007, 15 (13) 4482-4497 10.1016/j.bmc.2007.04.023
106. Kaatz, G. W.; Moudgal, V. V.; Seo, S. M.; Kristiansen, J. E. Phenothiazines and Thioxanthenes Inhibit Multidrug Efflux Pump Activity in Staphylococcus Aureus Antimicrob. Agents Chemother. 2003, 47 (2) 719-726 10.1128/AAC.47.2.719-726.2003
107. Baroni, M.; Cruciani, G.; Sciabola, S.; Perruccio, F.; Mason, J. S. A Common Reference Framework for Analyzing/Comparing Proteins and Ligands. Fingerprints for Ligands And Proteins (FLAP): Theory and Application J. Chem. Inf. Model. 2007, 47 (2) 279-294 10.1021/ci600253e
108. Kalle, A. M.; Rizvi, A. Inhibition of Bacterial Multidrug Resistance by Celecoxib, a Cyclooxygenase-2 Inhibitor Antimicrob. Agents Chemother. 2011, 55 (1) 439-442 10.1128/AAC.00735-10
109. Bharate, J. B.; Singh, S.; Wani, A.; Sharma, S.; Joshi, P.; Khan, I. A.; Kumar, A.; Vishwakarma, R. A.; Bharate, S. B. Discovery of 4-Acetyl-3-(4-Fluorophenyl)-1-(P-Tolyl)-5-Methylpyrrole as a Dual Inhibitor of Human P-Glycoprotein and Staphylococcus Aureus Nor A Efflux Pump Org. Biomol. Chem. 2015, 13 (19) 5424-5431 10.1039/C5OB00246J
110. Kalia, N. P.; Mahajan, P.; Mehra, R.; Nargotra, A.; Sharma, J. P.; Koul, S.; Khan, I. A. Capsaicin, a Novel Inhibitor of the NorA Efflux Pump, Reduces the Intracellular Invasion of Staphylococcus Aureus J. Antimicrob. Chemother. 2012, 67 (10) 2401-2408 10.1093/jac/dks232
111. Sharma, S.; Kumar, M.; Sharma, S.; Nargotra, A.; Koul, S.; Khan, I. A. Piperine as an Inhibitor of Rv1258c, a Putative Multidrug Efflux Pump of Mycobacterium Tuberculosis J. Antimicrob. Chemother. 2010, 65 (8) 1694-1701 10.1093/jac/dkq186
112. Michalet, S.; Cartier, G.; David, B.; Mariotte, A.-M.; Dijoux-franca, M.-G.; Kaatz, G. W.; Stavri, M.; Gibbons, S. N-Caffeoylphenalkylamide Derivatives as Bacterial Efflux Pump Inhibitors Bioorg. Med. Chem. Lett. 2007, 17 (6) 1755-1758 10.1016/j.bmcl.2006.12.059
113. Badmaev, V.; Majeed, M.; Norkus, E. P. Piperine, an Alkaloid Derived from Black Pepper Increases Serum Response of Beta-Carotene during 14-Days of Oral Beta-Carotene Supplementation Nutr. Res. (N. Y., NY, U. S.) 1999, 19 (3) 381-388 10.1016/S0271-5317(99)00007-X
114. Khan, I. A.; Mirza, Z. M.; Kumar, A.; Verma, V.; Qazi, G. N. Piperine, a Phytochemical Potentiator of Ciprofloxacin against Staphylococcus Aureus Antimicrob. Agents Chemother. 2006, 50 (2) 810-812 10.1128/AAC.50.2.810-812.2006
115. Nargotra, A.; Sharma, S.; Koul, J. L.; Sangwan, P. L.; Khan, I. A.; Kumar, A.; Taneja, S. C.; Koul, S. Quantitative Structure Activity Relationship (QSAR) of Piperine Analogs for Bacterial NorA Efflux Pump Inhibitors Eur. J. Med. Chem. 2009, 44 (10) 4128-4135 10.1016/j.ejmech.2009.05.004
116. Kumar, A.; Khan, I. A.; Koul, S.; Koul, J. L.; Taneja, S. C.; Ali, I.; Ali, F.; Sharma, S.; Mirza, Z. M.; Kumar, M.; Sangwan, P. L.; Gupta, P.; Thota, N.; Qazi, G. N. Novel Structural Analogues of Piperine as Inhibitors of the NorA Efflux Pump of Staphylococcus Aureus J. Antimicrob. Chemother. 2008, 61 (6) 1270-1276 10.1093/jac/dkn088
117. Sangwan, P. L.; Koul, J. L.; Koul, S.; Reddy, M. V.; Thota, N.; Khan, I. A.; Kumar, A.; Kalia, N. P.; Qazi, G. N. Piperine Analogs as Potent Staphylococcus Aureus NorA Efflux Pump Inhibitors Bioorg. Med. Chem. 2008, 16 (22) 9847-9857 10.1016/j.bmc.2008.09.042
118. Han, Y.; Tan, T. M. C.; Lim, L.-Y. Effects of Capsaicin on P-Gp Function and Expression in Caco-2 Cells Biochem. Pharmacol. 2006, 71 (12) 1727-1734 10.1016/j.bcp.2006.03.024
119. Tintino, S. R.; Oliveira-Tintino, C. D. M.; Campina, F. F.; Silva, R. L. P.; do S. Costa, M.; Menezes, I. R. A.; Calixto-Junior, J. T.; Siqueira-Junior, J. P.; Coutinho, H. D. M.; Leal-Balbino, T. C.; Balbino, V. Q. Evaluation of the Tannic Acid Inhibitory Effect against the NorA Efflux Pump of Staphylococcus Aureus Microb. Pathog. 2016, 97, 9-13 10.1016/j.micpath.2016.04.003
120. Opperman, T. J.; Nguyen, S. T. Recent Advances toward a Molecular Mechanism of Efflux Pump Inhibition Front. Microbiol. 2015, 6, 421 10.3389/fmicb.2015.00421
121. Murakami, S.; Nakashima, R.; Yamashita, E.; Matsumoto, T.; Yamaguchi, A. Crystal Structures of a Multidrug Transporter Reveal a Functionally Rotating Mechanism Nature 2006, 443 (7108) 173-179 10.1038/nature05076
122. Sennhauser, G.; Bukowska, M. A.; Briand, C.; Grütter, M. G. Crystal Structure of the Multidrug Exporter MexB from Pseudomonas Aeruginosa J. Mol. Biol. 2009, 389 (1) 134-145 10.1016/j.jmb.2009.04.001
123. Nakashima, R.; Sakurai, K.; Yamasaki, S.; Hayashi, K.; Nagata, C.; Hoshino, K.; Onodera, Y.; Nishino, K.; Yamaguchi, A. Structural Basis for the Inhibition of Bacterial Multidrug Exporters Nature 2013, 500 (7460) 102-106 10.1038/nature12300
124. Renau, T. E.; Léger, R.; Flamme, E. M.; Sangalang, J.; She, M. W.; Yen, R.; Gannon, C. L.; Griffith, D.; Chamberland, S.; Lomovskaya, O.; Hecker, S. J.; Lee, V. J.; Ohta, T.; Nakayama, K. Inhibitors of Efflux Pumps in Pseudomonas Aeruginosa Potentiate the Activity of the Fluoroquinolone Antibacterial Levofloxacin J. Med. Chem. 1999, 42 (24) 4928-4931 10.1021/jm9904598
125. Sonnet, P.; Izard, D.; Mullié, C. Prevalence of Efflux-Mediated Ciprofloxacin and Levofloxacin Resistance in Recent Clinical Isolates of Pseudomonas Aeruginosa and Its Reversal by the Efflux Pump Inhibitors 1-(1-Naphthylmethyl)-Piperazine and Phenylalanine-Arginine-β-Naphthylamide Int. J. Antimicrob. Agents 2012, 39 (1) 77-80 10.1016/j.ijantimicag.2011.08.005
126. Cortez-Cordova, J.; Kumar, A. Activity of the Efflux Pump Inhibitor Phenylalanine-Arginine β-Naphthylamide against the AdeFGH Pump of Acinetobacter Baumannii Int. J. Antimicrob. Agents 2011, 37 (5) 420-424 10.1016/j.ijantimicag.2011.01.006
127. Opperman, T. J.; Kwasny, S. M.; Kim, H.-S.; Nguyen, S. T.; Houseweart, C.; D'Souza, S.; Walker, G. C.; Peet, N. P.; Nikaido, H.; Bowlin, T. L. Characterization of a Novel Pyranopyridine Inhibitor of the AcrAB Efflux Pump of Escherichia Coli Antimicrob. Agents Chemother. 2014, 58 (2) 722-733 10.1128/AAC.01866-13
128. Vargiu, A. V.; Ruggerone, P.; Opperman, T. J.; Nguyen, S. T.; Nikaido, H. Molecular Mechanism of MBX2319 Inhibition of Escherichia Coli AcrB Multidrug Efflux Pump and Comparison with Other Inhibitors Antimicrob. Agents Chemother. 2014, 58 (10) 6224-6234 10.1128/AAC.03283-14
129. Nguyen, S. T.; Kwasny, S. M.; Ding, X.; Cardinale, S. C.; McCarthy, C. T.; Kim, H.-S.; Nikaido, H.; Peet, N. P.; Williams, J. D.; Bowlin, T. L.; Opperman, T. J. Structure-Activity Relationships of a Novel Pyranopyridine Series of Gram-Negative Bacterial Efflux Pump Inhibitors Bioorg. Med. Chem. 2015, 23 (9) 2024-2034 10.1016/j.bmc.2015.03.016
130. Yoshida, K.; Nakayama, K.; Kuru, N.; Kobayashi, S.; Ohtsuka, M.; Takemura, M.; Hoshino, K.; Kanda, H.; Zhang, J. Z.; Lee, V. J.; Watkins, W. J. MexAB-OprM Specific Efflux Pump Inhibitors in Pseudomonas Aeruginosa. Part 5: Carbon-Substituted Analogues at the C-2 Position Bioorg. Med. Chem. 2006, 14 (6) 1993-2004 10.1016/j.bmc.2005.10.043
131. Yoshida, K.; Nakayama, K.; Yokomizo, Y.; Ohtsuka, M.; Takemura, M.; Hoshino, K.; Kanda, H.; Namba, K.; Nitanai, H.; Zhang, J. Z.; Lee, V. J.; Watkins, W. J. MexAB-OprM Specific Efflux Pump Inhibitors in Pseudomonas Aeruginosa. Part 6: Exploration of Aromatic Substituents Bioorg. Med. Chem. 2006, 14 (24) 8506-8518 10.1016/j.bmc.2006.08.037
132. Yoshida, K.; Nakayama, K.; Ohtsuka, M.; Kuru, N.; Yokomizo, Y.; Sakamoto, A.; Takemura, M.; Hoshino, K.; Kanda, H.; Nitanai, H.; Namba, K.; Yoshida, K.; Imamura, Y.; Zhang, J. Z.; Lee, V. J.; Watkins, W. J. MexAB-OprM Specific Efflux Pump Inhibitors in Pseudomonas Aeruginosa. Part 7: Highly Soluble and in Vivo Active Quaternary Ammonium Analogue D13-9001, a Potential Preclinical Candidate Bioorg. Med. Chem. 2007, 15 (22) 7087-7097 10.1016/j.bmc.2007.07.039
133. Nakayama, K.; Kawato, H.; Watanabe, J.; Ohtsuka, M.; Yoshida, K.; Yokomizo, Y.; Sakamoto, A.; Kuru, N.; Ohta, T.; Hoshino, K.; Yoshida, K.; Ishida, H.; Cho, A.; Palme, M. H.; Zhang, J. Z.; Lee, V. J.; Watkins, W. J. MexAB-OprM Specific Efflux Pump Inhibitors in Pseudomonas Aeruginosa. Part 3: Optimization of Potency in the Pyridopyrimidine Series through the Application of a Pharmacophore Model Bioorg. Med. Chem. Lett. 2004, 14 (2) 475-479 10.1016/j.bmcl.2003.10.060
134. Nakayama, K.; Kuru, N.; Ohtsuka, M.; Yokomizo, Y.; Sakamoto, A.; Kawato, H.; Yoshida, K.; Ohta, T.; Hoshino, K.; Akimoto, K.; Itoh, J.; Ishida, H.; Cho, A.; Palme, M. H.; Zhang, J. Z.; Lee, V. J.; Watkins, W. J. MexAB-OprM Specific Efflux Pump Inhibitors in Pseudomonas Aeruginosa. Part 4: Addressing the Problem of Poor Stability due to Photoisomerization of an Acrylic Acid Moiety Bioorg. Med. Chem. Lett. 2004, 14 (10) 2493-2497 10.1016/j.bmcl.2004.03.007
135. Bohnert, J. A.; Kern, W. V. Selected Arylpiperazines Are Capable of Reversing Multidrug Resistance in Escherichia Coli Overexpressing RND Efflux Pumps Antimicrob. Agents Chemother. 2005, 49 (2) 849-852 10.1128/AAC.49.2.849-852.2005
136. Kern, W. V.; Steinke, P.; Schumacher, A.; Schuster, S.; Baum, H.; von Bohnert, J. A. Effect of 1-(1-Naphthylmethyl)-Piperazine, a Novel Putative Efflux Pump Inhibitor, on Antimicrobial Drug Susceptibility in Clinical Isolates of Escherichia Coli J. Antimicrob. Chemother. 2006, 57 (2) 339-343 10.1093/jac/dki445
137. Marchetti, M. L.; Errecalde, J.; Mestorino, N. Effect of 1-(1-Naphthylmethyl)-Piperazine on Antimicrobial Agent Susceptibility in Multidrug-Resistant Isogenic and Veterinary Escherichia Coli Field Strains J. Med. Microbiol. 2012, 61 (6) 786-792 10.1099/jmm.0.040204-0
138. Schumacher, A.; Steinke, P.; Bohnert, J. A.; Akova, M.; Jonas, D.; Kern, W. V. Effect of 1-(1-Naphthylmethyl)-Piperazine, a Novel Putative Efflux Pump Inhibitor, on Antimicrobial Drug Susceptibility in Clinical Isolates of Enterobacteriaceae Other than Escherichia Coli J. Antimicrob. Chemother. 2006, 57 (2) 344-348 10.1093/jac/dki446
139. Dwivedi, G. R.; Upadhyay, H. C.; Yadav, D. K.; Singh, V.; Srivastava, S. K.; Khan, F.; Darmwal, N. S.; Darokar, M. P. 4-Hydroxy-α-Tetralone and Its Derivative as Drug Resistance Reversal Agents in Multi Drug Resistant Escherichia Coli Chem. Biol. Drug Des. 2014, 83 (4) 482-492 10.1111/cbdd.12263
140. Piddock, L. J. V.; Garvey, M. I.; Rahman, M. M.; Gibbons, S. Natural and Synthetic Compounds such as Trimethoprim Behave as Inhibitors of Efflux in Gram-Negative Bacteria J. Antimicrob. Chemother. 2010, 65 (6) 1215-1223 10.1093/jac/dkq079
141. Rabin, N.; Zheng, Y.; Opoku-Temeng, C.; Du, Y.; Bonsu, E.; Sintim, H. O. Agents That Inhibit Bacterial Biofilm Formation Future Med. Chem. 2015, 7 (5) 647-671 10.4155/fmc.15.7
142. Kalia, V. C.; Purohit, H. J. Quenching the Quorum Sensing System: Potential Antibacterial Drug Targets Crit. Rev. Microbiol. 2011, 37 (2) 121-140 10.3109/1040841X.2010.532479
143. Chung, P. Y.; Toh, Y. S. Anti-Biofilm Agents: Recent Breakthrough against Multi-Drug Resistant Staphylococcus Aureus Pathog. Dis. 2014, 70 (3) 231-239 10.1111/2049-632X.12141
144. Reyes, S.; Huigens, R. W., III; Su, Z.; Simon, M. L.; Melander, C. Synthesis and Biological Activity of 2-Aminoimidazole Triazoles Accessed by Suzuki-Miyaura Cross-Coupling Org. Biomol. Chem. 2011, 9 (8) 3041-3049 10.1039/c0ob00925c
145. Yeagley, A. A.; Su, Z.; McCullough, K. D.; Worthington, R. J.; Melander, C. N-Substituted 2-Aminoimidazole Inhibitors of MRSA Biofilm Formation Accessed through Direct 1,3-Bis(tert-Butoxycarbonyl)guanidine Cyclization Org. Biomol. Chem. 2013, 11 (1) 130-137 10.1039/C2OB26469B
146. Su, Z.; Yeagley, A. A.; Su, R.; Peng, L.; Melander, C. Structural Studies on 4,5-Disubstituted 2-Aminoimidazole-Based Biofilm Modulators That Suppress Bacterial Resistance to β-Lactams ChemMedChem 2012, 7 (11) 2030-2039 10.1002/cmdc.201200350
147. Furlani, R. E.; Yeagley, A. A.; Melander, C. A Flexible Approach to 1,4-Di-Substituted 2-Aminoimidazoles That Inhibit and Disperse Biofilms and Potentiate the Effects of β-Lactams against Multi-Drug Resistant Bacteria Eur. J. Med. Chem. 2013, 62, 59-70 10.1016/j.ejmech.2012.12.005
148. Frei, R.; Breitbach, A. S.; Blackwell, H. E. 2-Aminobenzimidazole Derivatives Strongly Inhibit and Disperse Pseudomonas Aeruginosa Biofilms Angew. Chem., Int. Ed. 2012, 51 (21) 5226-5229 10.1002/anie.201109258
149. Maggio, B.; Raffa, D.; Raimondi, M. V.; Cascioferro, S.; Plescia, F.; Schillaci, D.; Cusimano, M. G.; Leonchiks, A.; Zhulenkovs, D.; Basile, L.; Daidone, G. Discovery of a New Class of Sortase A Transpeptidase Inhibitors to Tackle Gram-Positive Pathogens: 2-(2-Phenylhydrazinylidene)alkanoic Acids and Related Derivatives Molecules 2016, 21 (2) 241 10.3390/molecules21020241
150. Cascioferro, S.; Maggio, B.; Raffa, D.; Raimondi, M. V.; Cusimano, M. G.; Schillaci, D.; Manachini, B.; Leonchiks, A.; Daidone, G. A New Class of Phenylhydrazinylidene Derivatives as Inhibitors of Staphylococcus Aureus Biofilm Formation Med. Chem. Res. 2016, 25 (5) 870-878 10.1007/s00044-016-1535-9
151. Cascioferro, S.; Maggio, B.; Raffa, D.; Raimondi, M. V.; Cusimano, M. G.; Schillaci, D.; Manachini, B.; Plescia, F.; Daidone, G. Synthesis and Biofilm Formation Reduction of Pyrazole-4-Carboxamide Derivatives in Some Staphylococcus Aureus Strains Eur. J. Med. Chem. 2016, 123, 58-68 10.1016/j.ejmech.2016.07.030
152. Liebens, V.; Gerits, E.; Knapen, W. J.; Swings, T.; Beullens, S.; Steenackers, H. P.; Robijns, S.; Lippell, A.; O'Neill, A. J.; Veber, M.; Fröhlich, M.; Krona, A.; Lövenklev, M.; Corbau, R.; Marchand, A.; Chaltin, P.; De Brucker, K.; Thevissen, K.; Cammue, B. P.; Fauvart, M.; Verstraeten, N.; Michiels, J. Identification and Characterization of an Anti-Pseudomonal Dichlorocarbazol Derivative Displaying Anti-Biofilm Activity Bioorg. Med. Chem. Lett. 2014, 24 (23) 5404-5408 10.1016/j.bmcl.2014.10.039
153. Hodnik, Ž.; Łoś, J. M.; Žula, A.; Zidar, N.; Jakopin, Ž.; Łoś, M.; Sollner Dolenc, M.; Ilaš, J.; Wȩgrzyn, G.; Peterlin Mašič, L.; Kikelj, D. Inhibition of Biofilm Formation by Conformationally Constrained Indole-Based Analogues of the Marine Alkaloid Oroidin Bioorg. Med. Chem. Lett. 2014, 24 (11) 2530-2534 10.1016/j.bmcl.2014.03.094
154. Schillaci, D.; Maggio, B.; Raffa, D.; Daidone, G.; Cascioferro, S.; Cusimano, M. G.; Raimondi, M. V. 4-Diazopyrazole Derivatives as Potential New Antibiofilm Agents Chemotherapy 2008, 54 (6) 456-462 10.1159/000159271
155. Raimondi, M. V.; Maggio, B.; Raffa, D.; Plescia, F.; Cascioferro, S.; Cancemi, G.; Schillaci, D.; Cusimano, M. G.; Vitale, M.; Daidone, G. Synthesis and Anti-Staphylococcal Activity of New 4-Diazopyrazole Derivatives Eur. J. Med. Chem. 2012, 58, 64-71 10.1016/j.ejmech.2012.09.041
156. Nagender, P.; Malla Reddy, G.; Naresh Kumar, R.; Poornachandra, Y.; Ganesh Kumar, C.; Narsaiah, B. Synthesis, Cytotoxicity, Antimicrobial and Anti-Biofilm Activities of Novel pyrazolo[3,4-B]pyridine and Pyrimidine Functionalized 1,2,3-Triazole Derivatives Bioorg. Med. Chem. Lett. 2014, 24 (13) 2905-2908 10.1016/j.bmcl.2014.04.084
157. Singh, B.; Bhat, H. R.; Kumawat, M. K.; Singh, U. P. Structure-Guided Discovery of 1,3,5-Triazine-Pyrazole Conjugates as Antibacterial and Antibiofilm Agent against Pathogens Causing Human Diseases with Favorable Metabolic Fate Bioorg. Med. Chem. Lett. 2014, 24 (15) 3321-3325 10.1016/j.bmcl.2014.05.103
158. Cascioferro, S.; Raimondi, M. V.; Cusimano, M. G.; Raffa, D.; Maggio, B.; Daidone, G.; Schillaci, D. Pharmaceutical Potential of Synthetic and Natural Pyrrolomycins Molecules 2015, 20 (12) 21658-21671 10.3390/molecules201219797
159. Del Franco, M.; Paone, L.; Novati, R.; Giacomazzi, C. G.; Bagattini, M.; Galotto, C.; Montanera, P. G.; Triassi, M.; Zarrilli, R. Molecular Epidemiology of Carbapenem Resistant Enterobacteriaceae in Valle d'Aosta Region, Italy, Shows the Emergence of KPC-2 Producing Klebsiella Pneumoniae Clonal Complex 101 (ST101 and ST1789) BMC Microbiol. 2015, 15 (1) 260 10.1186/s12866-015-0597-z
160. Lujan, S. A.; Guogas, L. M.; Ragonese, H.; Matson, S. W.; Redinbo, M. R. Disrupting Antibiotic Resistance Propagation by Inhibiting the Conjugative DNA Relaxase Proc. Natl. Acad. Sci. U. S. A. 2007, 104 (30) 12282-12287 10.1073/pnas.0702760104
161. Nash, R. P.; McNamara, D. E.; Ballentine, W. K., III; Matson, S. W.; Redinbo, M. R. Investigating the Impact of Bisphosphonates and Structurally Related Compounds on Bacteria Containing Conjugative Plasmids Biochem. Biophys. Res. Commun. 2012, 424 (4) 697-703 10.1016/j.bbrc.2012.07.012
162. Edwards, J. S.; Betts, L.; Frazier, M. L.; Pollet, R. M.; Kwong, S. M.; Walton, W. G.; Ballentine, W. K.; Huang, J. J.; Habibi, S.; Del Campo, M.; Meier, J. L.; Dervan, P. B.; Firth, N.; Redinbo, M. R. Molecular Basis of Antibiotic Multiresistance Transfer in Staphylococcus Aureus Proc. Natl. Acad. Sci. U. S. A. 2013, 110 (8) 2804-2809 10.1073/pnas.1219701110
163. Fernandez-Lopez, R.; Machón, C.; Longshaw, C. M.; Martin, S.; Molin, S.; Zechner, E. L.; Espinosa, M.; Lanka, E.; de la Cruz, F. Unsaturated Fatty Acids Are Inhibitors of Bacterial Conjugation Microbiology 2005, 151 (11) 3517-3526 10.1099/mic.0.28216-0
164. Getino, M.; Sanabria-Ríos, D. J.; Fernández-López, R.; Campos-Gómez, J.; Sánchez-López, J. M.; Fernández, A.; Carballeira, N. M.; de la Cruz, F. Synthetic Fatty Acids Prevent Plasmid-Mediated Horizontal Gene Transfer mBio 2015, 6 (5) e01032-15 10.1128/mBio.01032-15
165. Bjarnsholt, T.; Ciofu, O.; Molin, S.; Givskov, M.; Høiby, N. Applying Insights from Biofilm Biology to Drug Development-Can a New Approach Be Developed? Nat. Rev. Drug Discovery 2013, 12 (10) 791-808 10.1038/nrd4000
166. Kourtesi, C.; Ball, A. R.; Huang, Y.-Y.; Jachak, S. M.; Vera, D. M. A.; Khondkar, P.; Gibbons, S.; Hamblin, M. R.; Tegos, G. P. Microbial Efflux Systems and Inhibitors: Approaches to Drug Discovery and the Challenge of Clinical Implementation Open Microbiol. J. 2013, 7, 34-52 10.2174/1874285801307010034
167. Garrison, A. T.; Bai, F.; Abouelhassan, Y.; Paciaroni, N. G.; Jin, S.; Huigens, R. W., III Bromophenazine Derivatives with Potent Inhibition, Dispersion and Eradication Activities against Staphylococcus Aureus Biofilms RSC Adv. 2014, 5 (2) 1120-1124 10.1039/C4RA08728C
168. Tillotson, G. S.; Theriault, N. New and Alternative Approaches to Tackling Antibiotic Resistance F1000Prime Rep. 2013, 5, 51 10.12703/P5-51
169. Ball, A. P.; Geddes, A. M.; Davey, P. G.; Farrell, I. D.; Brookes, G. R. Clavulanic Acid and Amoxycillin: A Clinical, Bacteriological, and Pharmacological Study Lancet 1980, 315, 620-623 10.1016/S0140-6736(80)91118-6
170. Kuye, O.; Teal, J.; DeVries, V. G.; Morrow, C. A.; Tally, F. P. Safety Profile of Piperacillin/Tazobactam in Phase I and III Clinical Studies J. Antimicrob. Chemother. 1993, 31, 113-124 10.1093/jac/31.suppl-A.113
171. Motohiro, T.; Tanaka, K.; Koga, T.; Shimada, Y.; Tomita, N.; Sakata, Y.; Fujimoto, T.; Nishiyama, T.; Ishimoto, K.; Tominaga, K. Fundamental and clinical studies of sulbactam/cefoperazone in the pediatric field Jpn. J. Antibiot. 1984, 37 (10) 1898-1918
172. Levasseur, P.; Girard, A.-M.; Lavallade, L.; Miossec, C.; Pace, J.; Coleman, K. Efficacy of a Ceftazidime-Avibactam Combination in a Murine Model of Septicemia Caused by Enterobacteriaceae Species Producing AmpC or Extended-Spectrum β-Lactamases Antimicrob. Agents Chemother. 2014, 58 (11) 6490-6495 10.1128/AAC.03579-14
173. Pournaras, S.; Poulou, A.; Tsakris, A. Inhibitor-Based Methods for the Detection of KPC Carbapenemase-Producing Enterobacteriaceae in Clinical Practice by Using Boronic Acid Compounds J. Antimicrob. Chemother. 2010, 65 (7) 1319-1321 10.1093/jac/dkq124