Skip to content
2000
image of A Comprehensive Review on Discovery, Development, the Chemistry of Quinolones, and Their Antimicrobial Resistance

Abstract

Quinolones, discovered in the 1970s, have played a critical role in revolutionizing the treatment of bacterial infections due to their broad-spectrum antimicrobial activity. Over the decades, these compounds have been extensively studied, resulting in the development of numerous new derivatives. This review explores the history and development of quinolones, focusing on their Structure-Activity Relationship (SAR), mechanisms of action, and the challenges posed by antimicrobial resistance. The key resistance mechanisms include mutations in DNA gyrase and topoisomerase IV, which reduce drug binding, plasma-mediated mechanisms, and chromosomal changes that decrease drug uptake or retention. These mechanisms highlight the need for innovative approaches to design quinolones to overcome these resistance pathways. This review also provides an understanding of the SAR of quinolones and, by integrating historical advancements and current challenges, it provides a foundation for the development of next-generation quinolone derivatives with improved efficacy and minimized resistance.

© 2025 Bentham Science Publishers
Loading

Article metrics loading...

/content/journals/ctmc/10.2174/0115680266355989250730072511
2025-08-05
2025-10-28

  • From This Site

    /content/journals/ctmc/10.2174/0115680266355989250730072511
    dcterms_title,dcterms_subject,pub_keyword
    -contentType:Contributor -contentType:Concept -contentType:Institution
    10
    5
Loading full text...

Full text loading...

References

  1. Lesher G.Y. Froelich E.J. Gruett M.D. Bailey J.H. Brundage R.P. 1, 8-Naphthyridine derivatives. A new class of chemotherapeutic agents. J. Med. Pharm. Chem. 1962 5 5 1063 1065 10.1021/jm01240a021 14056431
    [Google Scholar]
  2. Tillotson G.S. Quinolones: Structure-activity relationships and future predictions. J. Med. Microbiol. 1996 44 5 320 324 10.1099/00222615‑44‑5‑320 8636945
    [Google Scholar]
  3. Cook T.M. Brown K.G. Boyle J.V. Goss W.A. Bactericidal action of nalidixic acid on Bacillus subtilis. J. Bacteriol. 1966 92 5 1510 1514 10.1128/jb.92.5.1510‑1514.1966 4958883
    [Google Scholar]
  4. Oliphant C.M. Green G.M. Quinolones: A comprehensive review. Am. Fam. Physician 2002 65 3 455 464 11858629
    [Google Scholar]
  5. Pham T.D.M. Ziora Z.M. Blaskovich M.A.T. Quinolone antibiotics. MedChemComm 2019 10 10 1719 1739 10.1039/C9MD00120D 31803393
    [Google Scholar]
  6. Emmerson A.M. Jones A.M. The quinolones: Decades of development and use. J. Antimicrob. Chemother. 2003 51 90001 Suppl. 1 13 20 10.1093/jac/dkg208 12702699
    [Google Scholar]
  7. Vardanyan R Hruby V Synthesis of essential drugs. Elsevier 2006
    [Google Scholar]
  8. Desai N.C. Dodiya A.M. Synthesis, characterization and in vitro antimicrobial screening of quinoline nucleus containing 1,3,4-oxadiazole and 2-azetidinone derivatives. J. Saudi Chem. Soc. 2014 18 5 425 431 10.1016/j.jscs.2011.09.005
    [Google Scholar]
  9. Metwally K.A. Abdel-Aziz L.M. Lashine E.S.M. Husseiny M.I. Badawy R.H. Hydrazones of 2-aryl-quinoline-4-carboxylic acid hydrazides: Synthesis and preliminary evaluation as antimicrobial agents. Bioorg. Med. Chem. 2006 14 24 8675 8682 10.1016/j.bmc.2006.08.022 16949294
    [Google Scholar]
  10. Moussaoui O. El Hadrami E.M. Benjalloune Touimi G. Bennani B. Ben Tama A. Chakroune S. Boukir A. Synthesis of a new serie of quinoline-carboxamides based on methylated aminoesters: NMR characterization and antimicrobial activity. Mediterr. J. Chem. 2019 9 4 326 336 10.13171/mjc941911231077sc
    [Google Scholar]
  11. Appelbaum P.C. Hunter P.A. The fluoroquinolone antibacterials: Past, present and future perspectives. Int. J. Antimicrob. Agents 2000 16 1 5 15 10.1016/S0924‑8579(00)00192‑8 11185413
    [Google Scholar]
  12. Shivaraj Y. Naveen M.H. Vijayakumar G.R. Kumar D.B.A. Design, synthesis and antibacterial activity studies of novel quinoline carboxamide derivatives. J. Korean Chem. Soc. 2013 57 2 241 245 10.5012/jkcs.2013.57.2.241
    [Google Scholar]
  13. Roma G. Grossi G. Di Braccio M. Piras D. Ballabeni V. Tognolini M. Bertoni S. Barocelli E. 1,8-Naphthyridines VII. New substituted 5-amino[1,2,4]triazolo[4,3-a][1,8]naphthyridine-6-carboxamides and their isosteric analogues, exhibiting notable anti-inflammatory and/or analgesic activities, but no acute gastrolesivity. Eur. J. Med. Chem. 2008 43 8 1665 1680 10.1016/j.ejmech.2007.10.010 18045747
    [Google Scholar]
  14. Sliman F. Blairvacq M. Durieu E. Meijer L. Rodrigo J. Desmaële D. Identification and structure–activity relationship of 8-hydroxy-quinoline-7-carboxylic acid derivatives as inhibitors of Pim-1 kinase. Bioorg. Med. Chem. Lett. 2010 20 9 2801 2805 10.1016/j.bmcl.2010.03.061 20363627
    [Google Scholar]
  15. Vachharajani P.R. Solanki M.J. Dubal G.G. Shah V.H. Synthesis of some novel 1, 3, 4-oxadiazole and its anti-bacterial and anti-fungal activity. Arch. Appl. Sci. Res. 2011 3 1 280 285
    [Google Scholar]
  16. Velu A.B. Chen G.W. Hsieh P.T. Horng J.T. Hsu J.T.A. Hsieh H.P. Chen T.C. Weng K.F. Shih S.R. BPR-3P0128 inhibits RNA-dependent RNA polymerase elongation and VPg uridylylation activities of Enterovirus 71. Antiviral Res. 2014 112 18 25 10.1016/j.antiviral.2014.10.003 25448086
    [Google Scholar]
  17. Zarghi A. Ghodsi R. Design, synthesis, and biological evaluation of ketoprofen analogs as potent cyclooxygenase-2 inhibitors. Bioorg. Med. Chem. 2010 18 16 5855 5860 10.1016/j.bmc.2010.06.094 20650641
    [Google Scholar]
  18. Garudachari B. Satyanarayana M.N. Thippeswamy B. Shivakumar C.K. Shivananda K.N. Hegde G. Isloor A.M. Synthesis, characterization and antimicrobial studies of some new quinoline incorporated benzimidazole derivatives. Eur. J. Med. Chem. 2012 54 900 906 10.1016/j.ejmech.2012.05.027 22732060
    [Google Scholar]
  19. Tedesco R. Shaw A.N. Bambal R. Chai D. Concha N.O. Darcy M.G. Dhanak D. Fitch D.M. Gates A. Gerhardt W.G. Halegoua D.L. Han C. Hofmann G.A. Johnston V.K. Kaura A.C. Liu N. Keenan R.M. Lin-Goerke J. Sarisky R.T. Wiggall K.J. Zimmerman M.N. Duffy K.J. 3-(1,1-dioxo-2H-(1,2,4)-benzothiadiazin-3-yl)-4-hydroxy-2(1H)-quinolinones, potent inhibitors of hepatitis C virus RNA-dependent RNA polymerase. J. Med. Chem. 2006 49 3 971 983 10.1021/jm050855s 16451063
    [Google Scholar]
  20. Kaur K. Jain M. Reddy R.P. Jain R. Quinolines and structurally related heterocycles as antimalarials. Eur. J. Med. Chem. 2010 45 8 3245 3264 10.1016/j.ejmech.2010.04.011 20466465
    [Google Scholar]
  21. Eswaran S. Adhikari A.V. Shetty N.S. Synthesis and antimicrobial activities of novel quinoline derivatives carrying 1,2,4-triazole moiety. Eur. J. Med. Chem. 2009 44 11 4637 4647 10.1016/j.ejmech.2009.06.031 19647905
    [Google Scholar]
  22. Narayan G.K. Ganesh K.S. Akashdeen M.S. Ballal Mamatha M.M. Synthesis, antimicrobial evaluation and docking studies of novel quinoline carboxamide analogs. Int. J. Pharm. Sci. Rev. Res. 2016 41 2 344 348
    [Google Scholar]
  23. Emami S Shafiei A Foroumadi AR Quinolones: Recent structural and clinical developments. Iran J Pharm Res 2005 3
    [Google Scholar]
  24. Lode H. Potential interactions of the extended-spectrum fluoroquinolones with the CNS. Drug Saf. 1999 21 2 123 135 10.2165/00002018‑199921020‑00005 10456380
    [Google Scholar]
  25. Brossi A. Gessner W.P. Fritz R.R. Bembenek M.E. Abell C.W. Interaction of monoamine oxidase B with analogs of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine derived from prodine-type analgesics. J. Med. Chem. 1986 29 4 444 445 10.1021/jm00154a002 3485717
    [Google Scholar]
  26. Marble D.A. Bosso J.A. Norfloxacin: A quinoline antibiotic. Drug Intell. Clin. Pharm. 1986 20 4 261 266 10.1177/106002808602000402 3516615
    [Google Scholar]
  27. Holmes B. Brogden R.N. Richards D.M. Norfloxacin. A review of its antibacterial activity, pharmacokinetic properties and therapeutic use. Drugs 1985 30 6 482 513 10.2165/00003495‑198530060‑00003 3908074
    [Google Scholar]
  28. Gomez C.M. Kouznetsov V.V. Recent developments on antimicrobial quinoline chemistry. Microbial Pathogens and Strategies for Combating Them: Science, Technology and Education FORMATEX 2013 666 677
    [Google Scholar]
  29. Aldred K.J. Kerns R.J. Osheroff N. Mechanism of quinolone action and resistance. Biochemistry 2014 53 10 1565 1574 10.1021/bi5000564 24576155
    [Google Scholar]
  30. Reece R.J. Maxwell A. DNA gyrase: Structure and function. Crit. Rev. Biochem. Mol. Biol. 1991 26 3-4 335 375 10.3109/10409239109114072 1657531
    [Google Scholar]
  31. Drlica K. Zhao X. DNA gyrase, topoisomerase IV, and the 4-quinolones. Microbiol. Mol. Biol. Rev. 1997 61 3 377 392 9293187
    [Google Scholar]
  32. Roca J. The mechanisms of DNA topoisomerases. Trends Biochem. Sci. 1995 20 4 156 160 10.1016/S0968‑0004(00)88993‑8 7770916
    [Google Scholar]
  33. Peng H. Marians K.J. The interaction of Escherichia coli topoisomerase IV with DNA. J. Biol. Chem. 1995 270 42 25286 25290 10.1074/jbc.270.42.25286 7559669
    [Google Scholar]
  34. Kato J. Nishimura Y. Imamura R. Niki H. Hiraga S. Suzuki H. New topoisomerase essential for chromosome segregation in E. coli. Cell 1990 63 2 393 404 10.1016/0092‑8674(90)90172‑B 2170028
    [Google Scholar]
  35. Kato J. Suzuki H. Ikeda H. Purification and characterization of DNA topoisomerase IV in Escherichia coli. J. Biol. Chem. 1992 267 36 25676 25684 10.1016/S0021‑9258(18)35660‑6 1334483
    [Google Scholar]
  36. Kampranis S.C. Maxwell A. Conversion of DNA gyrase into a conventional type II topoisomerase. Proc. Natl. Acad. Sci. USA 1996 93 25 14416 14421 10.1073/pnas.93.25.14416 8962066
    [Google Scholar]
  37. Peng H. Marians K.J. Escherichia coli topoisomerase IV. Purification, characterization, subunit structure, and subunit interactions. J. Biol. Chem. 1993 268 32 24481 24490 10.1016/S0021‑9258(20)80551‑1 8227000
    [Google Scholar]
  38. Gellert M. Mizuuchi K. O’Dea M.H. Itoh T. Tomizawa J.I. Nalidixic acid resistance: A second genetic character involved in DNA gyrase activity. Proc. Natl. Acad. Sci. USA 1977 74 11 4772 4776 10.1073/pnas.74.11.4772 337300
    [Google Scholar]
  39. Snyder M. Drlica K. DNA gyrase on the bacterial chromosome: DNA cleavage induced by oxolinic acid. J. Mol. Biol. 1979 131 2 287 302 10.1016/0022‑2836(79)90077‑9 226717
    [Google Scholar]
  40. Sugino A. Peebles C.L. Kreuzer K.N. Cozzarelli N.R. Mechanism of action of nalidixic acid: Purification of Escherichia coli nalA gene product and its relationship to DNA gyrase and a novel nicking-closing enzyme. Proc. Natl. Acad. Sci. USA 1977 74 11 4767 4771 10.1073/pnas.74.11.4767 200930
    [Google Scholar]
  41. Khodursky A.B. Zechiedrich E.L. Cozzarelli N.R. Topoisomerase IV is a target of quinolones in Escherichia coli. Proc. Natl. Acad. Sci. USA 1995 92 25 11801 11805 10.1073/pnas.92.25.11801 8524852
    [Google Scholar]
  42. Aedo S. Tse-Dinh Y.C. Isolation and quantitation of topoisomerase complexes accumulated on Escherichia coli chromosomal DNA. Antimicrob. Agents Chemother. 2012 56 11 5458 5464 10.1128/AAC.01182‑12 22869559
    [Google Scholar]
  43. Drlica K. Hiasa H. Kerns R. Malik M. Mustaev A. Zhao X. Quinolones: Action and resistance updated. Curr. Top. Med. Chem. 2009 9 11 981 998 10.2174/156802609789630947 19747119
    [Google Scholar]
  44. Tenover F.C. Mechanisms of antimicrobial resistance in bacteria. Am. J. Med. 2006 119 6 Suppl. 1 S3 S10 10.1016/j.amjmed.2006.03.011 16735149
    [Google Scholar]
  45. McManus M.C. Mechanisms of bacterial resistance to antimicrobial agents. Am. J. Health Syst. Pharm. 1997 54 12 1420 1433 10.1093/ajhp/54.12.1420 9194989
    [Google Scholar]
  46. Drlica K Zhao X Malik M Salz T Kerns R. Fluoroquinolone resistance: Mechanisms, restrictive dosing, and anti-mutant screening strategies for new compounds. Antibiotic Discovery and Development Springer Boston, MA 2012 485 514 10.1007/978‑1‑4614‑1400‑1_14
    [Google Scholar]
  47. García-Rey C. Aguilar L. Baquero F. Influences of different factors on prevalence of ciprofloxacin resistance in Streptococcus pneumoniae in Spain. Antimicrob. Agents Chemother. 2000 44 12 3481 3482 10.1128/AAC.44.12.3481‑3482.2000 11185492
    [Google Scholar]
  48. Baquero F. Beltren J.M. Loza E. A review of antibiotic resistance patterns of Streptococcus pneumoniae in Europe. J. Antimicrob. Chemother. 1991 28 Suppl. C 31 38 10.1093/jac/28.suppl_C.31 1787127
    [Google Scholar]
  49. Bronzwaer S.L.A.M. Cars O. Buchholz U. Mölstad S. Goettsch W. Veldhuijzen I.K. Kool J.L. Sprenger M.J.W. Degener J.E. The relationship between antimicrobial use and antimicrobial resistance in Europe. Emerg. Infect. Dis. 2002 8 3 278 282 10.3201/eid0803.010192 11927025
    [Google Scholar]
  50. Sahm D.F. Peterson D.E. Critchley I.A. Thornsberry C. Analysis of ciprofloxacin activity against Streptococcus pneumoniae after 10 years of use in the United States. Antimicrob. Agents Chemother. 2000 44 9 2521 2524 10.1128/AAC.44.9.2521‑2524.2000 10952606
    [Google Scholar]
  51. Hooper D.C. New uses for new and old quinolones and the challenge of resistance. Clin. Infect. Dis. 2000 30 2 243 254 10.1086/313677 10671323
    [Google Scholar]
  52. Asrestrup F.M. Jensen N.E. Jorsal S.E. Neilsen T.K. Emergence of resistance to fluoroquinolones among bacteria causing infections in food animals in Denmark. Vet. Rec. 2000 146 3 76 78 10.1136/vr.146.3.76 10674696
    [Google Scholar]
  53. Aarestrup F.M. Agersø Y. Ahrens P. Jørgensen J.C.Ø. Madsen M. Jensen L.B. Antimicrobial susceptibility and presence of resistance genes in staphylococci from poultry. Vet. Microbiol. 2000 74 4 353 364 10.1016/S0378‑1135(00)00197‑8 10831857
    [Google Scholar]
  54. Angulo F.J. Johnson K.R. Tauxe R. Cohen M.L. Origins and consequences of antimicrobial-resistant nontyphoidal Salmonella: implications for the use of fluoroquinolones in food animals. Microb. Drug Resist. 2000 6 1 77 83 10.1089/mdr.2000.6.77 10868811
    [Google Scholar]
  55. Engberg J. Aarestrup F.M. Taylor D.E. Gerner-Smidt P. Nachamkin I. Quinolone and macrolide resistance in Campylobacter jejuni and C. coli: resistance mechanisms and trends in human isolates. Emerg. Infect. Dis. 2001 7 1 24 34 10.3201/eid0701.010104 11266291
    [Google Scholar]
  56. Davidson R.J. Davis I. Willey B.M. Rizg K. Bolotin S. Porter V. Polsky J. Daneman N. McGeer A. Yang P. Scolnik D. Rowsell R. Imas O. Silverman M.S. Antimalarial therapy selection for quinolone resistance among Escherichia coli in the absence of quinolone exposure, in tropical South America. PLoS One 2008 3 7 2727 10.1371/journal.pone.0002727 18648533
    [Google Scholar]
  57. LeClerc J.E. Li B. Payne W.L. Cebula T.A. High mutation frequencies among Escherichia coli and Salmonella pathogens. Science 1996 274 5290 1208 1211 10.1126/science.274.5290.1208 8895473
    [Google Scholar]
  58. Negri M.C. Morosini M.I. Baquero M.R. Campo R. Blázquez J. Baquero F. Very low cefotaxime concentrations select for hypermutable Streptococcus pneumoniae populations. Antimicrob. Agents Chemother. 2002 46 2 528 530 10.1128/AAC.46.2.528‑530.2002 11796370
    [Google Scholar]
  59. Sniegowski P.D. Gerrish P.J. Lenski R.E. Evolution of high mutation rates in experimental populations of E. coli. Nature 1997 387 6634 703 705 10.1038/42701 9192894
    [Google Scholar]
  60. Jyssum K. Observations on two types of genetic instability in Escherichia coli. Acta Pathol. Microbiol. Scand. 1960 48 2 113 120 10.1111/j.1699‑0463.1960.tb04747.x 14408281
    [Google Scholar]
  61. Gross M.D. Siegel E.C. Incidence of mutator strains in Escherichia coli and coliforms in nature. Mutat. Mutat. Res. Lett. 1981 91 2 107 110 10.1016/0165‑7992(81)90081‑6 7019693
    [Google Scholar]
  62. Hooper D.C. Mode of action of fluoroquinolones. Drugs 1999 58 Suppl. 2 6 10 10.2165/00003495‑199958002‑00002 10553698
    [Google Scholar]
  63. Hooper D.C. Mechanisms of action of antimicrobials: Focus on fluoroquinolones. Clin. Infect. Dis. 2001 32 Suppl. 1 S9 S15 10.1086/319370 11249823
    [Google Scholar]
  64. Anderson V. Osheroff N. Type II topoisomerases as targets for quinolone antibacterials: Turning Dr. Jekyll into Mr. Hyde. Curr. Pharm. Des. 2001 7 5 337 353 10.2174/1381612013398013 11254893
    [Google Scholar]
  65. German N. Malik M. Rosen J.D. Drlica K. Kerns R.J. Use of gyrase resistance mutants to guide selection of 8-methoxy-quinazoline-2,4-diones. Antimicrob. Agents Chemother. 2008 52 11 3915 3921 10.1128/AAC.00330‑08 18765690
    [Google Scholar]
  66. Fournier B. Zhao X. Lu T. Drlica K. Hooper D.C. Selective targeting of topoisomerase IV and DNA gyrase in Staphylococcus aureus: Different patterns of quinolone-induced inhibition of DNA synthesis. Antimicrob. Agents Chemother. 2000 44 8 2160 2165 10.1128/AAC.44.8.2160‑2165.2000 10898691
    [Google Scholar]
  67. Price L.B. Vogler A. Pearson T. Busch J.D. Schupp J.M. Keim P. In vitro selection and characterization of Bacillus anthracis mutants with high-level resistance to ciprofloxacin. Antimicrob. Agents Chemother. 2003 47 7 2362 2365 10.1128/AAC.47.7.2362‑2365.2003 12821500
    [Google Scholar]
  68. Morgan-Linnell S.K. Becnel Boyd L. Steffen D. Zechiedrich L. Mechanisms accounting for fluoroquinolone resistance in Escherichia coli clinical isolates. Antimicrob. Agents Chemother. 2009 53 1 235 241 10.1128/AAC.00665‑08 18838592
    [Google Scholar]
  69. Li Z. Deguchi T. Yasuda M. Kawamura T. Kanematsu E. Nishino Y. Ishihara S. Kawada Y. Alteration in the GyrA subunit of DNA gyrase and the ParC subunit of DNA topoisomerase IV in quinolone-resistant clinical isolates of Staphylococcus epidermidis. Antimicrob. Agents Chemother. 1998 42 12 3293 3295 10.1128/AAC.42.12.3293 9835531
    [Google Scholar]
  70. Aldred K.J. McPherson S.A. Wang P. Kerns R.J. Graves D.E. Turnbough C.L. Jr Osheroff N. Drug interactions with Bacillus anthracis topoisomerase IV: biochemical basis for quinolone action and resistance. Biochemistry 2012 51 1 370 381 10.1021/bi2013905 22126453
    [Google Scholar]
  71. Aldred K.J. McPherson S.A. Turnbough C.L. Jr Kerns R.J. Osheroff N. Topoisomerase IV-quinolone interactions are mediated through a water-metal ion bridge: mechanistic basis of quinolone resistance. Nucleic Acids Res. 2013 41 8 4628 4639 10.1093/nar/gkt124 23460203
    [Google Scholar]
  72. Pan X.S. Gould K.A. Fisher L.M. Probing the differential interactions of quinazolinedione PD 0305970 and quinolones with gyrase and topoisomerase IV. Antimicrob. Agents Chemother. 2009 53 9 3822 3831 10.1128/AAC.00113‑09 19564360
    [Google Scholar]
  73. Anderson V.E. Zaniewski R.P. Kaczmarek F.S. Gootz T.D. Osheroff N. Action of quinolones against Staphylococcus aureus topoisomerase IV: basis for DNA cleavage enhancement. Biochemistry 2000 39 10 2726 2732 10.1021/bi992302n 10704224
    [Google Scholar]
  74. Pan X.S. Yague G. Fisher L.M. Quinolone resistance mutations in Streptococcus pneumoniae GyrA and ParC proteins: Mechanistic insights into quinolone action from enzymatic analysis, intracellular levels, and phenotypes of wild-type and mutant proteins. Antimicrob. Agents Chemother. 2001 45 11 3140 3147 10.1128/AAC.45.11.3140‑3147.2001 11600369
    [Google Scholar]
  75. Yague G. Morris J.E. Pan X.S. Gould K.A. Fisher L.M. Cleavable-complex formation by wild-type and quinolone-resistant Streptococcus pneumoniae type II topoisomerases mediated by gemifloxacin and other fluoroquinolones. Antimicrob. Agents Chemother. 2002 46 2 413 419 10.1128/AAC.46.2.413‑419.2002 11796351
    [Google Scholar]
  76. Pfeiffer E.S. Hiasa H. Determination of the primary target of a quinolone drug and the effect of quinolone resistance-conferring mutations by measuring quinolone sensitivity based on its mode of action. Antimicrob. Agents Chemother. 2007 51 9 3410 3412 10.1128/AAC.00362‑07 17606687
    [Google Scholar]
  77. Oppegard L.M. Streck K.R. Rosen J.D. Schwanz H.A. Drlica K. Kerns R.J. Hiasa H. Comparison of in vitro activities of fluoroquinolone-like 2,4- and 1,3-diones. Antimicrob. Agents Chemother. 2010 54 7 3011 3014 10.1128/AAC.00190‑10 20404126
    [Google Scholar]
  78. Willmott C.J. Maxwell A. A single point mutation in the DNA gyrase A protein greatly reduces binding of fluoroquinolones to the gyrase-DNA complex. Antimicrob. Agents Chemother. 1993 37 1 126 127 10.1128/AAC.37.1.126 8381633
    [Google Scholar]
  79. Anderson V.E. Gootz T.D. Osheroff N. Topoisomerase IV catalysis and the mechanism of quinolone action. J. Biol. Chem. 1998 273 28 17879 17885 10.1074/jbc.273.28.17879 9651393
    [Google Scholar]
  80. Anderson V.E. Zaniewski R.P. Kaczmarek F.S. Gootz T.D. Osheroff N. Quinolones inhibit DNA religation mediated by Staphylococcus aureus topoisomerase IV. Changes in drug mechanism across evolutionary boundaries. J. Biol. Chem. 1999 274 50 35927 35932 10.1074/jbc.274.50.35927 10585479
    [Google Scholar]
  81. Barnard F.M. Maxwell A. Interaction between DNA gyrase and quinolones: Effects of alanine mutations at GyrA subunit residues Ser(83) and Asp(87). Antimicrob. Agents Chemother. 2001 45 7 1994 2000 10.1128/AAC.45.7.1994‑2000.2001 11408214
    [Google Scholar]
  82. Martínez-Martínez L. Eliecer Cano M. Manuel Rodríguez-Martínez J. Calvo J. Pascual Á. Plasmid-mediated quinolone resistance. Expert Rev. Anti Infect. Ther. 2008 6 5 685 711 10.1586/14787210.6.5.685 18847406
    [Google Scholar]
  83. Rodríguez-Martínez J.M. Velasco C. Pascual Á. Cano M.E. Martínez-Martínez L. Martínez-Martínez L. Pascual Á. Plasmid-mediated quinolone resistance: An update. J. Infect. Chemother. 2011 17 2 149 182 10.1007/s10156‑010‑0120‑2 20886256
    [Google Scholar]
  84. Yoshida H. Kojima T. Yamagishi J. Nakamura S. Quinolone-resistant mutations of the gyrA gene of Escherichia coli. Mol. Gen. Genet. 1988 211 1 1 7 10.1007/BF00338386 2830458
    [Google Scholar]
  85. Colodner R. Keness Y. Chazan B. Raz R. Antimicrobial susceptibility of community-acquired uropathogens in northern Israel. Int. J. Antimicrob. Agents 2001 18 2 189 192 10.1016/S0924‑8579(01)00368‑5 11516944
    [Google Scholar]
  86. Hiasa H. The Glu-84 of the ParC subunit plays critical roles in both topoisomerase IV-quinolone and topoisomerase IV-DNA interactions. Biochemistry 2002 41 39 11779 11785 10.1021/bi026352v 12269820
    [Google Scholar]
  87. Garau J. Xercavins M. Rodríguez-Carballeira M. Gómez-Vera J.R. Coll I. Vidal D. Llovet T. Ruíz-Bremón A. Emergence and dissemination of quinolone-resistant Escherichia coli in the community. Antimicrob. Agents Chemother. 1999 43 11 2736 2741 10.1128/AAC.43.11.2736 10543756
    [Google Scholar]
  88. Jacoby GA Strahilevitz J Hooper DC Plasmid‐mediated quinolone resistance. Plasmids: Biology and Impact in Biotechnology and Discovery Wiley 2015 475 503 10.1128/9781555818982.ch25
    [Google Scholar]
  89. Strahilevitz J. Jacoby G.A. Hooper D.C. Robicsek A. Plasmid-mediated quinolone resistance: A multifaceted threat. Clin. Microbiol. Rev. 2009 22 4 664 689 10.1128/CMR.00016‑09 19822894
    [Google Scholar]
  90. Hiramatsu K. Igarashi M. Morimoto Y. Baba T. Umekita M. Akamatsu Y. Curing bacteria of antibiotic resistance: Reverse antibiotics, a novel class of antibiotics in nature. Int. J. Antimicrob. Agents 2012 39 6 478 485 10.1016/j.ijantimicag.2012.02.007 22534508
    [Google Scholar]
  91. Yamane K. Wachino J. Suzuki S. Kimura K. Shibata N. Kato H. Shibayama K. Konda T. Arakawa Y. New plasmid-mediated fluoroquinolone efflux pump, QepA, found in an Escherichia coli clinical isolate. Antimicrob. Agents Chemother. 2007 51 9 3354 3360 10.1128/AAC.00339‑07 17548499
    [Google Scholar]
  92. Cattoir V. Poirel L. Nordmann P. Plasmid-mediated quinolone resistance pump QepA2 in an Escherichia coli isolate from France. Antimicrob. Agents Chemother. 2008 52 10 3801 3804 10.1128/AAC.00638‑08 18644958
    [Google Scholar]
  93. Guillard T. Cambau E. Chau F. Massias L. de Champs C. Fantin B. Ciprofloxacin treatment failure in a murine model of pyelonephritis due to an AAC(6′)-Ib-cr-producing Escherichia coli strain susceptible to ciprofloxacin in vitro. Antimicrob. Agents Chemother. 2013 57 12 5830 5835 10.1128/AAC.01489‑13 24018262
    [Google Scholar]
  94. Sun H.I. Jeong D.U. Lee J.H. Wu X. Park K.S. Lee J.J. Jeong B.C. Lee S.H. A novel family (QnrAS) of plasmid-mediated quinolone resistance determinant. Int. J. Antimicrob. Agents 2010 36 6 578 579 10.1016/j.ijantimicag.2010.08.009 20947314
    [Google Scholar]
  95. Xiong X. Bromley E.H.C. Oelschlaeger P. Woolfson D.N. Spencer J. Structural insights into quinolone antibiotic resistance mediated by pentapeptide repeat proteins: conserved surface loops direct the activity of a Qnr protein from a Gram-negative bacterium. Nucleic Acids Res. 2011 39 9 3917 3927 10.1093/nar/gkq1296 21227918
    [Google Scholar]
  96. Martínez-Martínez L. Pascual A. Jacoby G.A. Quinolone resistance from a transferable plasmid. Lancet 1998 351 9105 797 799 10.1016/S0140‑6736(97)07322‑4 9519952
    [Google Scholar]
  97. Ling T.K.W. Xiong J. Yu Y. Lee C.C. Ye H. Hawkey P.M. Multicenter antimicrobial susceptibility survey of gram-negative bacteria isolated from patients with community-acquired infections in the People’s Republic of China. Antimicrob. Agents Chemother. 2006 50 1 374 378 10.1128/AAC.50.1.374‑378.2006 16377716
    [Google Scholar]
  98. Neuhauser M.M. Weinstein R.A. Rydman R. Danziger L.H. Karam G. Quinn J.P. Antibiotic resistance among gram-negative bacilli in US intensive care units: implications for fluoroquinolone use. JAMA 2003 289 7 885 888 10.1001/jama.289.7.885 12588273
    [Google Scholar]
  99. Robicsek A. Strahilevitz J. Jacoby G.A. Macielag M. Abbanat D. Hye Park C. Bush K. Hooper D.C. Fluoroquinolone-modifying enzyme: A new adaptation of a common aminoglycoside acetyltransferase. Nat. Med. 2006 12 1 83 88 10.1038/nm1347 16369542
    [Google Scholar]
  100. Tran J.H. Jacoby G.A. Mechanism of plasmid-mediated quinolone resistance. Proc. Natl. Acad. Sci. USA 2002 99 8 5638 5642 10.1073/pnas.082092899 11943863
    [Google Scholar]
  101. Cambau E. Lascols C. Sougakoff W. Bébéar C. Bonnet R. Cavallo J.D. Gutmann L. Ploy M.C. Jarlier V. Soussy C.J. Robert J. Occurrence of qnrA-positive clinical isolates in French teaching hospitals during 2002–2005. Clin. Microbiol. Infect. 2006 12 10 1013 1020 10.1111/j.1469‑0691.2006.01529.x 16961639
    [Google Scholar]
  102. Cheung T.K.M. Chu Y.W. Chu M.Y. Ma C.H. Yung R.W.H. Kam K.M. Plasmid-mediated resistance to ciprofloxacin and cefotaxime in clinical isolates of Salmonella enterica serotype Enteritidis in Hong Kong. J. Antimicrob. Chemother. 2005 56 3 586 589 10.1093/jac/dki250 16033804
    [Google Scholar]
  103. Nordmann P. Poirel L. Emergence of plasmid-mediated resistance to quinolones in Enterobacteriaceae. J. Antimicrob. Chemother. 2005 56 3 463 469 10.1093/jac/dki245 16020539
    [Google Scholar]
  104. Poirel L. Rodriguez-Martinez J.M. Mammeri H. Liard A. Nordmann P. Origin of plasmid-mediated quinolone resistance determinant QnrA. Antimicrob. Agents Chemother. 2005 49 8 3523 3525 10.1128/AAC.49.8.3523‑3525.2005 16048974
    [Google Scholar]
  105. Whichard J.M. Gay K. Stevenson J.E. Joyce K.J. Cooper K.L. Omondi M. Medalla F. Jacoby G.A. Barrett T.J. Human Salmonella and concurrent decreased susceptibility to quinolones and extended-spectrum cephalosporins. Emerg. Infect. Dis. 2007 13 11 1681 1688 10.3201/eid1311.061438 18217551
    [Google Scholar]
  106. Hata M. Suzuki M. Matsumoto M. Takahashi M. Sato K. Ibe S. Sakae K. Cloning of a novel gene for quinolone resistance from a transferable plasmid in Shigella flexneri 2b. Antimicrob. Agents Chemother. 2005 49 2 801 803 10.1128/AAC.49.2.801‑803.2005 15673773
    [Google Scholar]
  107. Cattoir V. Nordmann P. Silva-Sanchez J. Espinal P. Poirel L. ISEcp1-mediated transposition of qnrB-like gene in Escherichia coli. Antimicrob. Agents Chemother. 2008 52 8 2929 2932 10.1128/AAC.00349‑08 18519717
    [Google Scholar]
  108. Sjölund-Karlsson M. Howie R. Rickert R. Krueger A. Tran T.T. Zhao S. Ball T. Haro J. Pecic G. Joyce K. Fedorka-Cray P.J. Whichard J.M. McDermott P.F. Plasmid-mediated quinolone resistance among non-Typhi Salmonella enterica isolates, USA. Emerg. Infect. Dis. 2010 16 11 1789 1791 10.3201/eid1611.100464 21029547
    [Google Scholar]
  109. Jacoby G.A. Walsh K.E. Mills D.M. Walker V.J. Oh H. Robicsek A. Hooper D.C. qnrB, another plasmid-mediated gene for quinolone resistance. Antimicrob. Agents Chemother. 2006 50 4 1178 1182 10.1128/AAC.50.4.1178‑1182.2006 16569827
    [Google Scholar]
  110. Wang M. Jacoby G.A. Mills D.M. Hooper D.C. SOS regulation of qnrB expression. Antimicrob. Agents Chemother. 2009 53 2 821 823 10.1128/AAC.00132‑08 19029320
    [Google Scholar]
  111. Malik M. Marks K.R. Mustaev A. Zhao X. Chavda K. Kerns R.J. Drlica K. Fluoroquinolone and quinazolinedione activities against wild-type and gyrase mutant strains of Mycobacterium smegmatis. Antimicrob. Agents Chemother. 2011 55 5 2335 2343 10.1128/AAC.00033‑11 21383100
    [Google Scholar]
  112. Kehrenberg C. Friederichs S. de Jong A. Schwarz S. Novel Variant of the qnrB Gene, qnrB12, in Citrobacter werkmanii. Antimicrob. Agents Chemother. 2008 52 3 1206 1207 10.1128/AAC.01042‑07 18086833
    [Google Scholar]
  113. Saki M. Farajzadeh Sheikh A. Seyed-Mohammadi S. Asareh Zadegan Dezfuli A. Shahin M. Tabasi M. Veisi H. Keshavarzi R. Khani P. Occurrence of plasmid-mediated quinolone resistance genes in Pseudomonas aeruginosa strains isolated from clinical specimens in southwest Iran: A multicentral study. Sci. Rep. 2022 12 1 2296 10.1038/s41598‑022‑06128‑4 35145139
    [Google Scholar]
  114. Furmanek-Blaszk B. Sektas M. Rybak B. High prevalence of plasmid-mediated quinolone resistance among ESBL/AmpC-producing enterobacterales from free-living birds in Poland. Int. J. Mol. Sci. 2023 24 16 12804 10.3390/ijms241612804 37628984
    [Google Scholar]
  115. Robicsek A. Strahilevitz J. Sahm D.F. Jacoby G.A. Hooper D.C. qnr prevalence in ceftazidime-resistant Enterobacteriaceae isolates from the United States. Antimicrob. Agents Chemother. 2006 50 8 2872 2874 10.1128/AAC.01647‑05 16870791
    [Google Scholar]
  116. Quiroga M.P. Andres P. Petroni A. Soler Bistué A.J.C. Guerriero L. Vargas L.J. Zorreguieta A. Tokumoto M. Quiroga C. Tolmasky M.E. Galas M. Centrón D. Complex class 1 integrons with diverse variable regions, including aac(6′)-Ib-cr, and a novel allele, qnrB10, associated with ISCR1 in clinical enterobacterial isolates from Argentina. Antimicrob. Agents Chemother. 2007 51 12 4466 4470 10.1128/AAC.00726‑07 17938184
    [Google Scholar]
  117. Tamang M.D. Seol S.Y. Oh J.Y. Kang H.Y. Lee J.C. Lee Y.C. Cho D.T. Kim J. Plasmid-mediated quinolone resistance determinants qnrA, qnrB, and qnrS among clinical isolates of Enterobacteriaceae in a Korean hospital. Antimicrob. Agents Chemother. 2008 52 11 4159 4162 10.1128/AAC.01633‑07 18725444
    [Google Scholar]
  118. Jacoby G.A. Mechanisms of resistance to quinolones. Clin. Infect. Dis. 2005 41 Suppl. 2 S120 S126 10.1086/428052 15942878
    [Google Scholar]
  119. Wang M. Guo Q. Xu X. Wang X. Ye X. Wu S. Hooper D.C. Wang M. New plasmid-mediated quinolone resistance gene, qnrC, found in a clinical isolate of Proteus mirabilis. Antimicrob. Agents Chemother. 2009 53 5 1892 1897 10.1128/AAC.01400‑08 19258263
    [Google Scholar]
  120. Cavaco L.M. Hasman H. Xia S. Aarestrup F.M. qnrD, a novel gene conferring transferable quinolone resistance in Salmonella enterica serovar Kentucky and Bovismorbificans strains of human origin. Antimicrob. Agents Chemother. 2009 53 2 603 608 10.1128/AAC.00997‑08 19029321
    [Google Scholar]
  121. Tran J.H. Jacoby G.A. Hooper D.C. Interaction of the plasmid-encoded quinolone resistance protein QnrA with Escherichia coli topoisomerase IV. Antimicrob. Agents Chemother. 2005 49 7 3050 3052 10.1128/AAC.49.7.3050‑3052.2005 15980397
    [Google Scholar]
  122. Tran J.H. Jacoby G.A. Hooper D.C. Interaction of the plasmid-encoded quinolone resistance protein Qnr with Escherichia coli DNA gyrase. Antimicrob. Agents Chemother. 2005 49 1 118 125 10.1128/AAC.49.1.118‑125.2005 15616284
    [Google Scholar]
  123. Shrestha R.K. Thapa A. Shrestha D. Pokhrel S. Aryal A. Adhikari R. Shrestha N. Dhoubhadel B.G. Parry C.M. Characterization of transferrable mechanisms of quinolone resistance (TMQR) among quinolone-resistant Escherichia coli and klebsiella pneumoniae causing urinary tract infection in nepalese children. BMC Pediatr. 2023 23 1 458 10.1186/s12887‑023‑04279‑5 37704964
    [Google Scholar]
  124. Hansen L.H. Sørensen S.J. Jørgensen H.S. Jensen L.B. The prevalence of the OqxAB multidrug efflux pump amongst olaquindox-resistant Escherichia coli in pigs. Microb. Drug Resist. 2005 11 4 378 382 10.1089/mdr.2005.11.378 16359198
    [Google Scholar]
  125. Kim H.B. Wang M. Park C.H. Kim E.C. Jacoby G.A. Hooper D.C. oqxAB encoding a multidrug efflux pump in human clinical isolates of Enterobacteriaceae. Antimicrob. Agents Chemother. 2009 53 8 3582 3584 10.1128/AAC.01574‑08 19528276
    [Google Scholar]
  126. Mitscher L.A. Bacterial topoisomerase inhibitors: Quinolone and pyridone antibacterial agents. Chem. Rev. 2005 105 2 559 592 10.1021/cr030101q 15700957
    [Google Scholar]
  127. Martínez-Martínez L. Pascual A. García I. Tran J. Jacoby G.A. Interaction of plasmid and host quinolone resistance. J. Antimicrob. Chemother. 2003 51 4 1037 1039 10.1093/jac/dkg157 12654766
    [Google Scholar]
  128. Poole K. Efflux pumps as antimicrobial resistance mechanisms. Ann. Med. 2007 39 3 162 176 10.1080/07853890701195262 17457715
    [Google Scholar]
  129. Goldman J.D. White D.G. Levy S.B. Multiple antibiotic resistance (mar) locus protects Escherichia coli from rapid cell killing by fluoroquinolones. Antimicrob. Agents Chemother. 1996 40 5 1266 1269 10.1128/AAC.40.5.1266 8723480
    [Google Scholar]
  130. Poirel L. Cattoir V. Nordmann P. Is plasmid-mediated quinolone resistance a clinically significant problem? Clin. Microbiol. Infect. 2008 14 4 295 297 10.1111/j.1469‑0691.2007.01930.x 18190576
    [Google Scholar]
  131. Wise R. Honeybourne D. Pharmacokinetics and pharmacodynamics of fluoroquinolones in the respiratory tract. Eur. Respir. J. 1999 14 1 221 229 10.1034/j.1399‑3003.1999.14a38.x 10489856
    [Google Scholar]
  132. Dalhoff A. Schmitz F.J. In vitro antibacterial activity and pharmacodynamics of new quinolones. Eur. J. Clin. Microbiol. Infect. Dis. 2003 22 4 203 221 10.1007/s10096‑003‑0907‑5 12687416
    [Google Scholar]
  133. Ball P. Fernald A. Tillotson G. Therapeutic advances of new fluoroquinolones. Expert Opin. Investig. Drugs 1998 7 5 761 783 10.1517/13543784.7.5.761 15991967
    [Google Scholar]
  134. Schentag J.J. Sparfloxacin: A review. Clin. Ther. 2000 22 4 372 387 10.1016/S0149‑2918(00)89007‑4 10823360
    [Google Scholar]
  135. Emami S. Shafiee A. Foroumadi A. Structural features of new quinolones and relationship to antibacterial activity against Gram-positive bacteria. Mini Rev. Med. Chem. 2006 6 4 375 386 10.2174/138955706776361493 16613574
    [Google Scholar]
  136. Andriole V.T. The quinolones: Past, present, and future. Clin. Infect. Dis. 2005 41 Suppl. 2 S113 S119 10.1086/428051 15942877
    [Google Scholar]
  137. Domagala J.M. Structure-activity and structure-side-effect relationships for the quinolone antibacterials. J. Antimicrob. Chemother. 1994 33 4 685 706 10.1093/jac/33.4.685 8056688
    [Google Scholar]
  138. Weller T.M.A. Andrews J.M. Jevons G. Wise R. The in vitro activity of BMS-284756, a new des-fluorinated quinolone. J. Antimicrob. Chemother. 2002 49 1 177 184 10.1093/jac/49.1.177 11751785
    [Google Scholar]
  139. Sarro A. Sarro G. Adverse reactions to fluoroquinolones. An overview on mechanistic aspects. Curr. Med. Chem. 2001 8 4 371 384 10.2174/0929867013373435 11172695
    [Google Scholar]
  140. Domagala J.M. Heifetz C.L. Hutt M.P. Mich T.F. Nichols J.B. Solomon M. Worth D.F. 1-Substituted 7-[3-[(ethylamino)methyl]-1-pyrrolidinyl]-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acids. New quantitative structure activity relationships at N1 for the quinolone antibacterials. J. Med. Chem. 1988 31 5 991 1001 10.1021/jm00400a017 2834557
    [Google Scholar]
  141. Chu D.T.W. Fernandes P.B. Claiborne A.K. Pihuleac E. Nordeen C.W. Maleczka R.E. Jr Pernet A.G. Synthesis and structure-activity relationships of novel arylfluoroquinolone antibacterial agents. J. Med. Chem. 1985 28 11 1558 1564 10.1021/jm00149a003 3934382
    [Google Scholar]
  142. Bryskier A. Chantot J.F. Classification and structure-activity relationships of fluoroquinolones. Drugs 1995 49 Suppl. 2 16 28 10.2165/00003495‑199500492‑00005 8549288
    [Google Scholar]
  143. Wolfson J.S. Hooper D.C. Fluoroquinolone antimicrobial agents. Clin. Microbiol. Rev. 1989 2 4 378 424 10.1128/CMR.2.4.378 2680058
    [Google Scholar]
  144. Mitsuhashi S Kojima T Nakanishi N Fujimoto T Goto O Miyusaki S Uematsu T Nakashima M Asahina Y Ishisaki T Susue S. Fluorinated quinolones—new quinolone antimicrobials. Progress in Drug Research 1992 9 147
    [Google Scholar]
  145. Burton M.J. Rajak S.N. Hu V.H. Ramadhani A. Habtamu E. Massae P. Tadesse Z. Callahan K. Emerson P.M. Khaw P.T. Jeffries D. Mabey D.C.W. Bailey R.L. Weiss H.A. Holland M.J. Pathogenesis of progressive scarring trachoma in Ethiopia and Tanzania and its implications for disease control: Two cohort studies. PLoS Negl. Trop. Dis. 2015 9 5 0003763 10.1371/journal.pntd.0003763 25970613
    [Google Scholar]
  146. Dhivya D. Vijayakumar B. A focus on quinolones and its medicinal importance. Int. J. Novel Trends Pharm. Sci. 2011 1 1 23 29
    [Google Scholar]
  147. Gootz T.D. Brighty K.E. Fluoroquinolone antibacterials: SAR, mechanism of action, resistance, and clinical aspects. Med. Res. Rev. 1996 16 5 433 486 10.1002/(SICI)1098‑1128(199609)16:5<433::AID‑MED3>3.0.CO;2‑W 8865150
    [Google Scholar]
  148. Goa K.L. Bryson H.M. Markham A. Sparfloxacin. Drugs 1997 53 4 700 725 10.2165/00003495‑199753040‑00010 9098667
    [Google Scholar]
  149. Ince D. Zhang X. Silver L.C. Hooper D.C. Dual targeting of DNA gyrase and topoisomerase IV: Target interactions of garenoxacin (BMS-284756, T-3811ME), a new desfluoroquinolone. Antimicrob. Agents Chemother. 2002 46 11 3370 3380 10.1128/AAC.46.11.3370‑3380.2002 12384338
    [Google Scholar]
  150. Kimura Y. Atarashi S. Kawakami K. Sato K. Hayakawa I. (Fluorocyclopropyl)quinolones. 2. Synthesis and stereochemical structure-activity relationships of chiral 7-(7-Amino-5-azaspiro[2.4]heptan-5-yl)-1-(2-fluorocyclopropyl)quinolone antibacterial agents. J. Med. Chem. 1994 37 20 3344 3352 10.1021/jm00046a019 7932562
    [Google Scholar]
  151. Bhanot S. Singh M. Chatterjee N. Yoshida A. Hayakawa I. Bures M.G. Shen L.L. The chemical and biological aspects of fluoroquinolones: Reality and dreams. Curr. Pharm. Des. 2001 7 5 311 335 10.2174/1381612013398059 11254892
    [Google Scholar]
  152. Yoshida T. Yamamoto Y. Orita H. Kakiuchi M. Takahashi Y. Itakura M. Kado N. Mitani K. Yasuda S. Kato H. Itoh Y. Studies on quinolone antibacterials. IV. Structure-activity relationships of antibacterial activity and side effects for 5- or 8-substituted and 5,8-disubstituted-7-(3-amino-1-pyrrolidinyl)-1-cyclopropyl-1, 4-dihydro-4-oxoquinoline-3-carboxylic acids. Chem. Pharm. Bull. 1996 44 5 1074 1085 10.1248/cpb.44.1074 8689718
    [Google Scholar]
  153. Brighty KE Gootz TD Chemistry and mechanism of action of the quinolone antibacterials. The quinolones Academic Press 2000 33 97 10.1016/B978‑012059517‑4/50003‑9
    [Google Scholar]
  154. Singh R. Swick M.C. Ledesma K.R. Yang Z. Hu M. Zechiedrich L. Tam V.H. Temporal interplay between efflux pumps and target mutations in development of antibiotic resistance in Escherichia coli. Antimicrob. Agents Chemother. 2012 56 4 1680 1685 10.1128/AAC.05693‑11 22232279
    [Google Scholar]
  155. Roychoudhury S. Ledoussal B. Non-fluorinated quinolones (NFQs): New antibacterials with unique properties against quinolone-resistant gram-positive pathogens. Curr. Drug Targets Infect. Disord. 2002 2 1 51 65 10.2174/1568005024605891 12462153
    [Google Scholar]
  156. Artico M. Mai A. Sbardella G. Massa S. Musiu C. Lostia S. Demontis F. La Colla P. Nitroquinolones with broad-spectrum antimycobacterial activity in vitro. Bioorg. Med. Chem. Lett. 1999 9 12 1651 1656 10.1016/S0960‑894X(99)00251‑6 10397494
    [Google Scholar]
  157. Cecchetti V. Fravolini A. Lorenzini M.C. Tabarrini O. Terni P. Xin T. Studies on 6-aminoquinolones: Synthesis and antibacterial evaluation of 6-amino-8-methylquinolones. J. Med. Chem. 1996 39 2 436 445 10.1021/jm950558v 8558512
    [Google Scholar]
  158. Sun J. Sakai S. Tauchi Y. Deguchi Y. Cheng G. Chen J. Morimoto K. Protonation equilibrium and lipophilicity of olamufloxacin (HSR-903), a newly synthesized fluoroquinolone antibacterial. Eur. J. Pharm. Biopharm. 2003 56 2 223 229 10.1016/S0939‑6411(03)00099‑7 12957636
    [Google Scholar]
  159. Bronson J. Barrett J. Quinolone, everninomycin, glycylcycline, carbapenem, lipopeptide and cephem antibacterials in clinical development. Curr. Med. Chem. 2001 8 14 1775 1793 10.2174/0929867013371653 11562293
    [Google Scholar]
  160. Hong C.Y. Discovery of gemifloxacin (Factive, LB20304a): A quinolone of new a generation. Farmaco 2001 56 1-2 41 44 10.1016/S0014‑827X(01)01017‑5 11347965
    [Google Scholar]
  161. Kim M.J. Yun H.J. Kang J.W. Kim S. Kwak J.H. Choi E.C. In vitro development of resistance to a novel fluoroquinolone, DW286, in methicillin-resistant Staphylococcus aureus clinical isolates. J. Antimicrob. Chemother. 2003 51 4 1011 1016 10.1093/jac/dkg162 12654771
    [Google Scholar]
  162. Yun H.J. Min Y.H. Jo Y.W. Shim M.J. Choi E.C. Increased antibacterial activity of DW286, a novel fluoronaphthyridone antibiotic, against Staphylococcus aureus strains with defined mutations in DNA gyrase and topoisomerase IV. Int. J. Antimicrob. Agents 2005 25 4 334 337 10.1016/j.ijantimicag.2004.11.013 15784314
    [Google Scholar]
  163. Laponogov I. Pan X.S. Veselkov D.A. McAuley K.E. Fisher L.M. Sanderson M.R. Structural basis of gate-DNA breakage and resealing by type II topoisomerases. PLoS One 2010 5 6 11338 10.1371/journal.pone.0011338 20596531
    [Google Scholar]
  164. Kim J.H. Kang J.A. Kim Y.G. Kim J.W. Lee J.H. Choi E.C. Kim B.K. In vitro and in vivo antibacterial efficacies of CFC-222, a new fluoroquinolone. Antimicrob. Agents Chemother. 1997 41 10 2209 2213 10.1128/AAC.41.10.2209 9333049
    [Google Scholar]
  165. Barry A.L. Fuchs P.C. Brown S.D. In vitro activities of three nonfluorinated quinolones against representative bacterial isolates. Antimicrob. Agents Chemother. 2001 45 6 1923 1927 10.1128/AAC.45.6.1923‑1927.2001 11353655
    [Google Scholar]
  166. Shen L.L. Mitscher L.A. Sharma P.N. O’Donnell T.J. Chu D.W.T. Cooper C.S. Rosen T. Pernet A.G. Mechanism of inhibition of DNA gyrase by quinolone antibacterials: A cooperative drug-DNA binding model. Biochemistry 1989 28 9 3886 3894 10.1021/bi00435a039 2546585
    [Google Scholar]
  167. Foroumadi A. Emami S. Davood A. Moshafi M.H. Sharifian A. Tabatabaie M. Farimani H.T. Sepehri G. Shafiee A. Synthesis and in‐vitro antibacterial activities of N‐substituted piperazinyl quinolones. Pharm. Pharmacol. Commun. 1997 3 12 559 563
    [Google Scholar]
  168. Mirzaei M. Foroumadi A. Synthesis and in-vitro antibacterial activity of <I>N</I>-piperazinyl quinolone derivatives with a 2-thienyl group. Pharm. Pharmacol. Commun. 2000 6 8 351 354 10.1211/146080800128736196
    [Google Scholar]
  169. Foroumadi A. Emami S. Mehni M. Moshafi M.H. Shafiee A. Synthesis and antibacterial activity of N-[2-(5-bromothiophen-2-yl)-2-oxoethyl] and N-[(2-5-bromothiophen-2-yl)-2-oximinoethyl] derivatives of piperazinyl quinolones. Bioorg. Med. Chem. Lett. 2005 15 20 4536 4539 10.1016/j.bmcl.2005.07.005 16115766
    [Google Scholar]
  170. Foroumadi A. Emami S. Hassanzadeh A. Rajaee M. Sokhanvar K. Moshafi M.H. Shafiee A. Synthesis and antibacterial activity of N-(5-benzylthio-1,3,4-thiadiazol-2-yl) and N-(5-benzylsulfonyl-1,3,4-thiadiazol-2-yl)piperazinyl quinolone derivatives. Bioorg. Med. Chem. Lett. 2005 15 20 4488 4492 10.1016/j.bmcl.2005.07.016 16105736
    [Google Scholar]
  171. Brighty K.E. Gootz T.D. The chemistry and biological profile of trovafloxacin. J. Antimicrob. Chemother. 1997 39 Suppl. 2 1 14 10.1093/jac/39.suppl_2.1 9222064
    [Google Scholar]
  172. Miyazaki E. Miyazaki M. Chen J.M. Chaisson R.E. Bishai W.R. Moxifloxacin (BAY12-8039), a new 8-methoxyquinolone, is active in a mouse model of tuberculosis. Antimicrob. Agents Chemother. 1999 43 1 85 89 10.1128/AAC.43.1.85 9869570
    [Google Scholar]
  173. Rubinstein E. History of quinolones and their side effects. Chemotherapy 2001 47 Suppl. 3 3 8 10.1159/000057838 11549783
    [Google Scholar]
  174. Chu D.T.W. Recent progress in novel macrolides, quinolones, and 2-pyridones to overcome bacterial resistance. Med. Res. Rev. 1999 19 6 497 520 10.1002/(SICI)1098‑1128(199911)19:6<497::AID‑MED3>3.0.CO;2‑R 10557367
    [Google Scholar]
  175. Dong Y. Xu C. Zhao X. Domagala J. Drlica K. Fluoroquinolone action against mycobacteria: effects of C-8 substituents on growth, survival, and resistance. Antimicrob. Agents Chemother. 1998 42 11 2978 2984 10.1128/AAC.42.11.2978 9797236
    [Google Scholar]
  176. Lu T. Zhao X. Drlica K. Gatifloxacin activity against quinolone-resistant gyrase: Allele-specific enhancement of bacteriostatic and bactericidal activities by the C-8-methoxy group. Antimicrob. Agents Chemother. 1999 43 12 2969 2974 10.1128/AAC.43.12.2969 10582891
    [Google Scholar]
  177. Zhao X. Wang J.Y. Xu C. Dong Y. Zhou J. Domagala J. Drlica K. Killing of Staphylococcus aureus by C-8-methoxy fluoroquinolones. Antimicrob. Agents Chemother. 1998 42 4 956 958 10.1128/AAC.42.4.956 9559820
    [Google Scholar]
  178. Roychoudhury S. Twinem T.L. Makin K.M. McIntosh E.J. Ledoussal B. Catrenich C.E. Activity of non-fluorinated quinolones (NFQs) against quinolone-resistant Escherichia coli and Streptococcus pneumoniae. J. Antimicrob. Chemother. 2001 48 1 29 36 10.1093/jac/48.1.29 11418510
    [Google Scholar]
  179. Park H.S. Kim H.J. Seol M.J. Choi D.R. Choi E.C. Kwak J.H. In vitro and in vivo antibacterial activities of DW-224a, a new fluoronaphthyridone. Antimicrob. Agents Chemother. 2006 50 6 2261 2264 10.1128/AAC.01407‑05 16723601
    [Google Scholar]
  180. Zhanel G.G. Ennis K. Vercaigne L. Walkty A. Gin A.S. Embil J. Smith H. Hoban D.J. A critical review of the fluoroquinolones: Focus on respiratory infections. Drugs 2002 62 1 13 59 10.2165/00003495‑200262010‑00002 11790155
    [Google Scholar]
  181. Ball P. Mandell L. Niki Y. Tillotson G. Comparative tolerability of the newer fluoroquinolone antibacterials. Drug Saf. 1999 21 5 407 421 10.2165/00002018‑199921050‑00005 10554054
    [Google Scholar]
  182. Binate G. Ismailov V. Yusubov N. Ganbarov K. Antimicrobial effect of (2-chloro-4-cyano-5-ethoxy-3,5-dioxopentan-2-yl) phosphonic acid against pathogenic bacteria and fungi. Adv. Biol. Earth Sci. 2024 9 2 223 227 10.62476/abes9223
    [Google Scholar]
  183. Wohlkonig A. Chan P.F. Fosberry A.P. Homes P. Huang J. Kranz M. Leydon V.R. Miles T.J. Pearson N.D. Perera R.L. Shillings A.J. Gwynn M.N. Bax B.D. Structural basis of quinolone inhibition of type IIA topoisomerases and target-mediated resistance. Nat. Struct. Mol. Biol. 2010 17 9 1152 1153 10.1038/nsmb.1892 20802486
    [Google Scholar]
  184. Aldred K.J. Schwanz H.A. Li G. McPherson S.A. Turnbough C.L. Jr Kerns R.J. Osheroff N. Overcoming target-mediated quinolone resistance in topoisomerase IV by introducing metal-ion-independent drug-enzyme interactions. ACS Chem. Biol. 2013 8 12 2660 2668 10.1021/cb400592n 24047414
    [Google Scholar]
  185. Tran T.P. Ellsworth E.L. Sanchez J.P. Watson B.M. Stier M.A. Showalter H.D.H. Domagala J.M. Shapiro M.A. Joannides E.T. Gracheck S.J. Nguyen D.Q. Bird P. Yip J. Sharadendu A. Ha C. Ramezani S. Wu X. Singh R. Structure–activity relationships of 3-aminoquinazolinediones, a new class of bacterial type-2 topoisomerase (DNA gyrase and topo IV) inhibitors. Bioorg. Med. Chem. Lett. 2007 17 5 1312 1320 10.1016/j.bmcl.2006.12.005 17196390
    [Google Scholar]
/content/journals/ctmc/10.2174/0115680266355989250730072511
Loading
A Comprehensive Review on Discovery, Development, the Chemistry of Quinolones, and Their Antimicrobial Resistance
Bentham Science Publishers ; https://doi.org/10.2174/0115680266355989250730072511
/content/journals/ctmc/10.2174/0115680266355989250730072511
/content/journals/ctmc/10.2174/0115680266355989250730072511
Loading

Data & Media loading...


  • Article Type:     Review Article
Keywords: SAR ; quinolones resistance mechanism ; quinolone chemistry ; plasmid-mediated quinolone resistance ; target-mediated quinolone resistance ; Quinolones

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test