{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T16:46:44Z","timestamp":1786985204546,"version":"build-2736575974"},"reference-count":47,"publisher":"Elsevier BV","license":[{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-017"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-037"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-012"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-029"},{"start":{"date-parts":[[2021,3,1]],"date-time":"2021-03-01T00:00:00Z","timestamp":1614556800000},"content-version":"stm-asf","delay-in-days":0,"URL":"https:\/\/doi.org\/10.15223\/policy-004"}],"funder":[{"DOI":"10.13039\/501100004482","name":"Kuwait University","doi-asserted-by":"publisher","award":["GS 01\/01"],"award-info":[{"award-number":["GS 01\/01"]}],"id":[{"id":"10.13039\/501100004482","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004482","name":"Kuwait University","doi-asserted-by":"publisher","award":["GS 03\/01"],"award-info":[{"award-number":["GS 03\/01"]}],"id":[{"id":"10.13039\/501100004482","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100013393","name":"Public Authority for Applied Education and Training","doi-asserted-by":"publisher","award":["HS-16-01"],"award-info":[{"award-number":["HS-16-01"]}],"id":[{"id":"10.13039\/501100013393","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic Chemistry"],"published-print":{"date-parts":[[2021,3]]},"DOI":"10.1016\/j.bioorg.2021.104658","type":"journal-article","created":{"date-parts":[[2021,1,21]],"date-time":"2021-01-21T17:40:03Z","timestamp":1611250803000},"page":"104658","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":29,"special_numbering":"C","title":["Antibiotic resistance and drug modification: Synthesis, characterization and bioactivity of newly modified potent ciprofloxacin derivatives"],"prefix":"10.1016","volume":"108","author":[{"given":"Abdulhakeem","family":"Alsughayer","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdel-Zaher A.","family":"Elassar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdulaziz A.","family":"Hasan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fakhreia","family":"Al Sagheer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"47","key":"10.1016\/j.bioorg.2021.104658_b0005","first-page":"1","article-title":"The multifaceted roles of antibiotics and antibiotic resistance in nature","volume":"4","author":"Sengupta","year":"2013","journal-title":"Front Microbiol."},{"key":"10.1016\/j.bioorg.2021.104658_b0010","doi-asserted-by":"crossref","first-page":"S71","DOI":"10.1093\/cid\/ciu392","article-title":"The future of antibiotics and resistance: a tribute to a career of leadership by John Bartlett","volume":"59","author":"Spellberg","year":"2014","journal-title":"Clin. Infect. Dis."},{"key":"10.1016\/j.bioorg.2021.104658_b0015","doi-asserted-by":"crossref","unstructured":"S. Li, Y. Liu, R. Ge, S. Yang, Y. Zhai, T. Hua, B. Stevy, B.S. Ondon, Q. Zhouand, F. Fengxiang Li, Microbial electro-Fenton: A promising system for antibiotics resistance genes degradation and energy generation, Sci. of the Total Envir., 699 (2020) 134160\u2013134168. https:\/\/doi.org\/10.1016\/j.scitotenv.2019.134160.","DOI":"10.1016\/j.scitotenv.2019.134160"},{"key":"10.1016\/j.bioorg.2021.104658_b0020","doi-asserted-by":"crossref","first-page":"129","DOI":"10.3855\/jidc.3573","article-title":"Bacteriophage therapy: a potential solution for the antibiotic resistance crisis","volume":"13","author":"Golkar","year":"2014","journal-title":"J. Infect. Dev. Ctries"},{"key":"10.1016\/j.bioorg.2021.104658_b0025","doi-asserted-by":"crossref","first-page":"185","DOI":"10.4161\/viru.22507","article-title":"New antibiotic agents in the pipeline and how they can overcome microbial resistance","volume":"4","author":"Gould","year":"2013","journal-title":"Virulence"},{"key":"10.1016\/j.bioorg.2021.104658_b0030","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1139\/cjm-2014-0063","article-title":"Something new: revisiting natural products in antibiotic drug discovery","volume":"60","author":"Wright","year":"2014","journal-title":"Can. J. Microbiol."},{"key":"10.1016\/j.bioorg.2021.104658_b0035","doi-asserted-by":"crossref","first-page":"3","DOI":"10.4161\/gmic.28027","article-title":"Off-label abuse of antibiotics by bacteria","volume":"5","author":"Viswanathan","year":"2014","journal-title":"Gut Microbes"},{"key":"10.1016\/j.bioorg.2021.104658_b0040","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1093\/emph\/eou024","article-title":"Antibiotic resistance management","volume":"1","author":"Read","year":"2014","journal-title":"Evol. Med. Public Health"},{"key":"10.1016\/j.bioorg.2021.104658_b0045","doi-asserted-by":"crossref","first-page":"314","DOI":"10.1177\/003335491412900402","article-title":"Antibiotic resistance: a public health crisis","volume":"129","author":"Lushniak","year":"2014","journal-title":"Public Health Rep."},{"key":"10.1016\/j.bioorg.2021.104658_b0050","doi-asserted-by":"crossref","first-page":"R1063","DOI":"10.1016\/j.cub.2013.11.057","article-title":"Antibiotics in crisis","volume":"23","author":"Gross","year":"2012","journal-title":"Curr. Biol."},{"key":"10.1016\/j.bioorg.2021.104658_b0055","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1016\/S1473-3099(11)70316-4","article-title":"The crisis of no new antibiotics- what is the way forward?","volume":"12","author":"Piddock","year":"2012","journal-title":"Lancet Infect. Dis."},{"key":"10.1016\/j.bioorg.2021.104658_b0060","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1093\/cid\/cit070","article-title":"Seven ways to preserve the miracle of antibiotics","volume":"56","author":"Bartlett","year":"2013","journal-title":"Clin. Infect. Dis."},{"key":"10.1016\/j.bioorg.2021.104658_b0065","doi-asserted-by":"crossref","unstructured":"A. Dalhoff, Global Fluoroquinolone Resistance Epidemiology and Implictions for Clinical Use, Interdisciplinary Perspectives on Infectious Diseases Volume 2012, Article ID 976273, 37 pages doi:10.1155\/2012\/976273.","DOI":"10.1155\/2012\/976273"},{"key":"10.1016\/j.bioorg.2021.104658_b0070","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1186\/s12879-015-1282-4","article-title":"Ciprofloxacin resistance in community- and hospital-acquired Escherichia coli urinary tract infections: a systematic review and meta-analysis of observational studies","volume":"15","author":"Fasugba","year":"2015","journal-title":"BMC Infect. Dis."},{"key":"10.1016\/j.bioorg.2021.104658_b0075","doi-asserted-by":"crossref","first-page":"145","DOI":"10.3389\/fpubh.2014.00145","article-title":"The antibiotic resistance crisis: causes, consequences, and management","volume":"2","author":"Michael","year":"2014","journal-title":"Front. Public Health"},{"key":"10.1016\/j.bioorg.2021.104658_b0080","doi-asserted-by":"crossref","unstructured":"L.S. Redgrave, S.B. Sutton, M.A. Webber, L. Piddock, Fluoroquinolone resistance: mechanisms, impact on bacteria, and role in evolutionary success, J. Trends Microbiol., 22 (2014) 438\u2013445. https:\/\/doi.org\/10.1016\/j.tim.2014.04.007.","DOI":"10.1016\/j.tim.2014.04.007"},{"key":"10.1016\/j.bioorg.2021.104658_b0085","doi-asserted-by":"crossref","first-page":"1565","DOI":"10.1021\/bi5000564","article-title":"Mechanism of quinolone action and resistance","volume":"53","author":"Aldred","year":"2014","journal-title":"Biochemistry"},{"key":"10.1016\/j.bioorg.2021.104658_b0090","doi-asserted-by":"crossref","first-page":"203","DOI":"10.3389\/fmicb.2011.00203","article-title":"Acquired antibiotic resistance genes: an overview","volume":"2","author":"van Hoek","year":"2011","journal-title":"Front. Microbiol."},{"key":"10.1016\/j.bioorg.2021.104658_b0095","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1128\/microbiolspec.PLAS-0006-2013","article-title":"Plasmid-mediated quinolone resistance","volume":"2","author":"Jacoby","year":"2014","journal-title":"Microbiol. Spectr."},{"key":"10.1016\/j.bioorg.2021.104658_b0100","doi-asserted-by":"crossref","first-page":"268","DOI":"10.3390\/molecules21040268","article-title":"The current case of quinolones: synthetic approaches and antibacterial activity","volume":"21","author":"Naeem","year":"2016","journal-title":"Molecules"},{"key":"10.1016\/j.bioorg.2021.104658_b0105","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1128\/CMR.05041-11","article-title":"Combination therapy for treatment of infections with gram-negative bacteria","volume":"25","author":"Tamma","year":"2012","journal-title":"Clin. Microbiol. Rev."},{"key":"10.1016\/j.bioorg.2021.104658_b0110","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1016\/j.jinf.2009.08.005","article-title":"Potential therapeutic failure of generic vancomycin in a liver transplant patient with MRSA peritonitis and bacteremia","volume":"59","author":"Rodriguez","year":"2009","journal-title":"J. Infect."},{"key":"10.1016\/j.bioorg.2021.104658_b0115","doi-asserted-by":"crossref","first-page":"3271","DOI":"10.1128\/AAC.01044-09","article-title":"Generic vancomycin products fail in vivo despite being pharmaceutical equivalents of the innovator","volume":"54","author":"Vesga","year":"2010","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.bioorg.2021.104658_b0120","doi-asserted-by":"crossref","first-page":"2659","DOI":"10.1128\/AAC.06012-11","article-title":"Therapeutic equivalence requires pharmaceutical, pharmacokinetic, and pharmacodynamic identities: true bioequivalence of a generic product of intravenous metronidazole","volume":"56","author":"Agudelo","year":"2012","journal-title":"Agents Chemother."},{"key":"10.1016\/j.bioorg.2021.104658_b0125","doi-asserted-by":"crossref","unstructured":"A. Bowen, J. Hurd, C. Hoover, Y. Khachadourian, E. Traphagen and E. Harvey, et al. V Importation and domestic transmission of Shigellasonnei resistant to ciprofloxacin- United States, May 2014-February 2015, Morb. Mortal. Wkly. Rep., 64, 318\u2013320. https:\/\/doi.org\/10.15585\/mmwr.mm644a3.","DOI":"10.15585\/mmwr.mm6444a3"},{"key":"10.1016\/j.bioorg.2021.104658_b0130","doi-asserted-by":"crossref","unstructured":"N. De Lappe, J. O\u2019connor, P. Garvey, P. Mckeown and M. Cormican, Ciprofloxacin- resistant Shigellasonnei associated with travel to India, Emerg. Infect. Dis. 21 (2015) 894\u2013896. https:\/\/doi.org\/10.3201\/eid2105.141184.","DOI":"10.3201\/eid2105.141184"},{"key":"10.1016\/j.bioorg.2021.104658_b0135","doi-asserted-by":"crossref","unstructured":"J.S. Kim, J.J. Kim, S.J. Kim, S.E. Jeon, K.Y. Seo, J.K., Choi, et al. Outbreak of ciprofloxacin-resistant Shigellasonnei associated with travel to Vietnam, Republic of Korea, Emerg. Infect. Dis., 21 (2015) 1247\u20131250. https:\/\/doi.org\/10.3201\/ eid2107.150363.","DOI":"10.3201\/eid2107.150363"},{"key":"10.1016\/j.bioorg.2021.104658_b0140","doi-asserted-by":"crossref","unstructured":"K. Jabeen, Fluoroquinolone-resistant tuberculosis: implications in settings with weak healthcare systems, S. Shakoor and R. Hasan, Int. J. Infect. Dis., 32 (2015) 118\u2013123. https:\/\/doi.org\/10.1016\/j.ijid.2015.01.006.","DOI":"10.1016\/j.ijid.2015.01.006"},{"key":"10.1016\/j.bioorg.2021.104658_b0145","doi-asserted-by":"crossref","unstructured":"Z. Cahana, A. Gilboa, R. Raz, Changes in susceptibility to ciprofloxacin in a community in northern Israel, Drugs 49-Suppl. 2 (1995) 173\u2013174. https:\/\/doi.org\/10.2165\/00003495-199500492-00030.","DOI":"10.2165\/00003495-199500492-00030"},{"key":"10.1016\/j.bioorg.2021.104658_b0150","doi-asserted-by":"crossref","unstructured":"G. Corti, F. Paradisi, E. Giganti, G. Buffini, E. Tortoli, L. Martelli, et al. Ciprofloxacin resistance in clinical isolates of Pseudomonas aeruginosa from Italian patients, Drugs, 49- Suppl. 2 (1995) 175\u2013176. https:\/\/doi.org\/10.2165\/00003495- 199500492-00031.","DOI":"10.2165\/00003495-199500492-00031"},{"key":"10.1016\/j.bioorg.2021.104658_b0155","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1093\/jac\/43.1.145","article-title":"Increasing fluoroquinolone resistance in Salmonella serotypes in Finland during 1995\u20131997","volume":"43","author":"Hakanen","year":"1999","journal-title":"J. Antimicrob. Chemother."},{"key":"10.1016\/j.bioorg.2021.104658_b0160","first-page":"238","article-title":"Increasing ciprofloxacin resistance among prevalent urinary tract bacterial isolates in Gaza Strip, Palestine","author":"El Astal","year":"2005","journal-title":"J. Biomed. Biotechnol."},{"key":"10.1016\/j.bioorg.2021.104658_b0165","first-page":"58","article-title":"Ciprofloxacin resistance pattern among bacteria isolated from patients with community-acquired urinary tract infection","author":"Reis","year":"2016","journal-title":"Rev. Inst. Med. Trop. Sao Paulo"},{"key":"10.1016\/j.bioorg.2021.104658_b0170","unstructured":"The crystallographic data for compounds 3 (ref. CCDC 1983444) and 10 (ref. CCDC 1983445) can be obtained on request from the director, Cambridge Crystallographic Data Centre, 12 Union Road, Cambridge CB2 1EW, UK."},{"key":"10.1016\/j.bioorg.2021.104658_b0175","doi-asserted-by":"crossref","unstructured":"S.K. Tiwari, X. Guo, Y. Huang, X. Zhou, H.H.K. Xu, B. Ren, X. Peng, M.D. Weir, M. Li, L. Chang, The inhibitory effect of quaternary ammonium salt on bacteria in root canal, Sci. Rep. 9 (2019) article no. 12463.","DOI":"10.1038\/s41598-019-48666-4"},{"issue":"1","key":"10.1016\/j.bioorg.2021.104658_b0180","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1054\/drup.1998.0068","article-title":"Mechanisms of fluoroquinolone resistance","volume":"2","author":"Hooper","year":"1999","journal-title":"Drug Resist. Updates"},{"issue":"supplement 2","key":"10.1016\/j.bioorg.2021.104658_b0185","article-title":"Mechanisms of action and resistance of older and newer fluoroquinolones","volume":"31","author":"Hooper","year":"2000","journal-title":"Clin. Infect. Dis."},{"key":"10.1016\/j.bioorg.2021.104658_b0190","doi-asserted-by":"crossref","unstructured":"D.C. Hooper, Fluoroquinolone resistance among Gram positive cocci, The Lancet Infect. Dis., 2 (2002) 530\u2013538. doi:10.1016\/s1473- 3099(02)00369- 9.","DOI":"10.1016\/S1473-3099(02)00369-9"},{"issue":"supplement","key":"10.1016\/j.bioorg.2021.104658_b0195","doi-asserted-by":"crossref","first-page":"S120","DOI":"10.1086\/428052","article-title":"Mechanisms of resistance to quinolones","volume":"41","author":"Jacoby","year":"2005","journal-title":"Clin. Infect. Dis."},{"issue":"supplement 1","key":"10.1016\/j.bioorg.2021.104658_b0200","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1093\/jac\/dkg207","article-title":"Mechanisms of quinolone action and microbial response","volume":"51","author":"Hawkey","year":"2003","journal-title":"J. Antimicrobial Chemoth."},{"key":"10.1016\/j.bioorg.2021.104658_b0205","doi-asserted-by":"crossref","first-page":"1818","DOI":"10.1086\/518003","article-title":"Impact of drug exposure intensity and duration of therapy on the emergence of Staphylococcus aureus resistance to a quinolone antimicrobial","volume":"195","author":"Tam","year":"2007","journal-title":"J. Infect. Dis."},{"key":"10.1016\/j.bioorg.2021.104658_b0210","doi-asserted-by":"crossref","unstructured":"T.D. Gootz, K.E. Brighty, Fluoroquinolone antibacterials: SAR, mechanism of action, resistance, and clinical aspects, Med. Res. Reviews, 16 (1996) 433-486 and references cited in https:\/\/doi.org\/10.1002\/(SICI)1098-1128(199609)16:5<433::AID-MED3>3.0.CO;2-W.","DOI":"10.1002\/(SICI)1098-1128(199609)16:5<433::AID-MED3>3.0.CO;2-W"},{"key":"10.1016\/j.bioorg.2021.104658_b0215","doi-asserted-by":"crossref","first-page":"1393","DOI":"10.1128\/AAC.37.7.1393","article-title":"Penetration of lipophilic agents with multiple protonation sites into bacterial cells: tetracyclines and fluoroquinolones as examples","volume":"37","author":"Nikaido","year":"1993","journal-title":"Antimicrob. Agents Chemother."},{"key":"10.1016\/j.bioorg.2021.104658_b0220","doi-asserted-by":"crossref","unstructured":"S.P. Cohen, D.C. Hooper, J.S. Wolfson, K.S. Souza, L.M. McMurray, S. 8. Levy, Endogenous active efflux of norfloxacin in susceptible Escherichia coli\u201d Antimicrob. Agents Chemother., 32 (1988) 1187. doi:10.1128\/aac.32.8.1187.","DOI":"10.1128\/AAC.32.8.1187"},{"key":"10.1016\/j.bioorg.2021.104658_b0225","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1128\/AAC.01617-06","article-title":"Quinolonemediated bacterial death","volume":"52","author":"Drlica","year":"2008","journal-title":"Antimicr. Agents and Chemother."},{"key":"10.1016\/j.bioorg.2021.104658_b0230","first-page":"377","article-title":"DNA gyrase, topoisomerase IV, and the 4-quinolones","volume":"61","author":"Drlica","year":"1997","journal-title":"Microbiol. Mol. Biol. Rev."},{"key":"10.1016\/j.bioorg.2021.104658_b0235","doi-asserted-by":"crossref","unstructured":"X. Zhao, C. Xu, J. Domagala, K. Drlica, DNA topoisomerase targets of the fluoroquinolones: a strategy for avoiding bacterial resistance, Proceedings of the National Academy of Sciences of the United States of America, vol. 94, no. 25, (1997) 13991\u2013 13996. Doi:10.1073\/pnas.94.25.13991.","DOI":"10.1073\/pnas.94.25.13991"}],"container-title":["Bioorganic Chemistry"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206821000341?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0045206821000341?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T08:12:12Z","timestamp":1758615132000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0045206821000341"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3]]},"references-count":47,"alternative-id":["S0045206821000341"],"URL":"https:\/\/doi.org\/10.1016\/j.bioorg.2021.104658","relation":{},"ISSN":["0045-2068"],"issn-type":[{"value":"0045-2068","type":"print"}],"subject":[],"published":{"date-parts":[[2021,3]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Antibiotic resistance and drug modification: Synthesis, characterization and bioactivity of newly modified potent ciprofloxacin derivatives","name":"articletitle","label":"Article Title"},{"value":"Bioorganic Chemistry","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bioorg.2021.104658","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2021 Elsevier Inc. All rights reserved.","name":"copyright","label":"Copyright"}],"article-number":"104658"}}