{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T06:11:01Z","timestamp":1789884661323,"version":"4.0.1"},"reference-count":34,"publisher":"Elsevier BV","issue":"11","license":[{"start":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T00:00:00Z","timestamp":1559347200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/tdm\/userlicense\/1.0\/"},{"start":{"date-parts":[[2019,6,1]],"date-time":"2019-06-01T00:00:00Z","timestamp":1559347200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/www.elsevier.com\/legal\/tdmrep-license"}],"funder":[{"name":"UTMB Technology Commercialization Program"},{"name":"Sanofi Innovation Awards"},{"name":"John Sealy Memorial Endowment Fund"},{"DOI":"10.13039\/100009259","name":"Institute for Translational Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009259","id-type":"DOI","asserted-by":"publisher"}]},{"name":"European Development Regional Fund"},{"name":"Instituto de Salud Carlos III, Proyectos de Investigaci\u00f3n en Salud","award":["PI15\/00489"],"award-info":[{"award-number":["PI15\/00489"]}]},{"name":"Proyectos de Desarrollo Tecnol\u00f3gico en Salud","award":["DTS17\/00130"],"award-info":[{"award-number":["DTS17\/00130"]}]},{"name":"Spanish Adenovirus Network","award":["BIO2015\/68990-REDT"],"award-info":[{"award-number":["BIO2015\/68990-REDT"]}]},{"name":"Nicol\u00e1s Monardes","award":["C-0059-2018"],"award-info":[{"award-number":["C-0059-2018"]}]}],"content-domain":{"domain":["elsevier.com","sciencedirect.com"],"crossmark-restriction":true},"short-container-title":["Bioorganic &amp; Medicinal Chemistry Letters"],"published-print":{"date-parts":[[2019,6]]},"DOI":"10.1016\/j.bmcl.2019.03.032","type":"journal-article","created":{"date-parts":[[2019,3,22]],"date-time":"2019-03-22T22:57:18Z","timestamp":1553295438000},"page":"1399-1402","update-policy":"https:\/\/doi.org\/10.1016\/elsevier_cm_policy","source":"Crossref","is-referenced-by-count":31,"title":["Discovery of niclosamide and its O-alkylamino-tethered derivatives as potent antibacterial agents against carbapenemase-producing and\/or colistin resistant Enterobacteriaceae isolates"],"prefix":"10.1016","volume":"29","author":[{"given":"Jimin","family":"Xu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mar\u00eda Eugenia","family":"Pach\u00f3n-Ib\u00e1\u00f1ez","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tania","family":"Cebrero-Cangueiro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haiying","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Javier","family":"S\u00e1nchez-C\u00e9spedes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2811-1090","authenticated-orcid":false,"given":"Jia","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"78","reference":[{"issue":"Suppl 1","key":"10.1016\/j.bmcl.2019.03.032_b0005","doi-asserted-by":"crossref","first-page":"S7","DOI":"10.1086\/655995","article-title":"Progress and challenges in implementing the research on ESKAPE pathogens","volume":"31","author":"Rice","year":"2010","journal-title":"Infect Control Hosp Epidemiol"},{"issue":"8","key":"10.1016\/j.bmcl.2019.03.032_b0010","doi-asserted-by":"crossref","first-page":"1079","DOI":"10.1086\/533452","article-title":"Federal funding for the study of antimicrobial resistance in nosocomial pathogens: no ESKAPE","volume":"197","author":"Rice","year":"2008","journal-title":"J Infect Dis"},{"issue":"3","key":"10.1016\/j.bmcl.2019.03.032_b0015","doi-asserted-by":"crossref","first-page":"297","DOI":"10.1586\/eri.13.12","article-title":"Clinical relevance of the ESKAPE pathogens","volume":"11","author":"Pendleton","year":"2013","journal-title":"Expert Rev Anti Infect Ther"},{"issue":"6","key":"10.1016\/j.bmcl.2019.03.032_b0020","first-page":"RA103-118","article-title":"Update on the antibacterial resistance crisis","volume":"13","author":"Croft","year":"2007","journal-title":"Med Sci Monit"},{"issue":"10","key":"10.1016\/j.bmcl.2019.03.032_b0025","doi-asserted-by":"crossref","first-page":"1791","DOI":"10.3201\/eid1710.110655","article-title":"Global spread of Carbapenemase-producing Enterobacteriaceae","volume":"17","author":"Nordmann","year":"2011","journal-title":"Emerg Infect Dis"},{"issue":"4","key":"10.1016\/j.bmcl.2019.03.032_b0030","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1128\/CMR.05035-11","article-title":"Carbapenemases in Klebsiella pneumoniae and other Enterobacteriaceae: an evolving crisis of global dimensions","volume":"25","author":"Tzouvelekis","year":"2012","journal-title":"Clin Microbiol Rev"},{"issue":"8","key":"10.1016\/j.bmcl.2019.03.032_b0035","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1586\/eri.12.78","article-title":"Colistin: an update on the antibiotic of the 21st century","volume":"10","author":"Biswas","year":"2012","journal-title":"Expert Rev Anti Infect Ther"},{"issue":"2","key":"10.1016\/j.bmcl.2019.03.032_b0040","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1016\/j.diagmicrobio.2015.06.011","article-title":"Tigecycline activity tested against carbapenem-resistant Enterobacteriaceae from 18 European nations: results from the SENTRY surveillance program (2010\u20132013)","volume":"83","author":"Sader","year":"2015","journal-title":"Diagn Microbiol Infect Dis"},{"issue":"5","key":"10.1016\/j.bmcl.2019.03.032_b0045","doi-asserted-by":"crossref","first-page":"624","DOI":"10.1017\/ice.2016.31","article-title":"Colistin and tigecycline resistance in carbapenem-resistant Enterobacteriaceae: checkmate to our last line of defense","volume":"37","author":"Kumar","year":"2016","journal-title":"Infect Control Hosp Epidemiol"},{"issue":"2","key":"10.1016\/j.bmcl.2019.03.032_b0050","doi-asserted-by":"crossref","first-page":"593","DOI":"10.1128\/AAC.01020-10","article-title":"Outbreak of colistin-resistant, carbapenem-resistant Klebsiella pneumoniae in metropolitan Detroit, Michigan","volume":"55","author":"Marchaim","year":"2011","journal-title":"Antimicrob Agents Chemother"},{"issue":"2","key":"10.1016\/j.bmcl.2019.03.032_b0055","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/0163-7258(82)90064-X","article-title":"The biology and toxicology of molluscicides, Bayluscide","volume":"19","author":"Andrews","year":"1982","journal-title":"Pharmacol Ther"},{"key":"10.1016\/j.bmcl.2019.03.032_b0060","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0099-5428(05)32002-8","article-title":"Niclosamide: comprehensive profile","volume":"32","author":"Al-Hadiya","year":"2005","journal-title":"Profiles Drug Subst Excip Relat Methodol"},{"issue":"5185","key":"10.1016\/j.bmcl.2019.03.032_b0065","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1038\/2211016a0","article-title":"Mechanism of action of reagents that uncouple oxidative phosphorylation","volume":"221","author":"Weinbach","year":"1969","journal-title":"Nature"},{"issue":"3809","key":"10.1016\/j.bmcl.2019.03.032_b0070","doi-asserted-by":"crossref","first-page":"1694","DOI":"10.1126\/science.158.3809.1694","article-title":"Salicylanilides: a new group of active uncouplers of oxidative phosphorylation","volume":"158","author":"Williamson","year":"1967","journal-title":"Science"},{"issue":"2","key":"10.1016\/j.bmcl.2019.03.032_b0075","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1016\/S0306-3623(96)00149-8","article-title":"The mechanisms of action of antiprotozoal and anthelmintic drugs in man","volume":"28","author":"Frayha","year":"1997","journal-title":"Gen Pharmacol"},{"issue":"1","key":"10.1016\/j.bmcl.2019.03.032_b0080","doi-asserted-by":"crossref","first-page":"8","DOI":"10.1016\/j.canlet.2014.04.003","article-title":"Multi-targeted therapy of cancer by niclosamide: a new application for an old drug","volume":"349","author":"Li","year":"2014","journal-title":"Cancer Lett"},{"key":"10.1016\/j.bmcl.2019.03.032_b0085","doi-asserted-by":"crossref","first-page":"89","DOI":"10.1016\/j.cellsig.2017.04.001","article-title":"Niclosamide: beyond an antihelminthic drug","volume":"41","author":"Chen","year":"2018","journal-title":"Cell Signal"},{"issue":"21","key":"10.1016\/j.bmcl.2019.03.032_b0090","doi-asserted-by":"crossref","first-page":"17530","DOI":"10.1074\/jbc.M112.359638","article-title":"Structure-activity analysis of niclosamide reveals potential role for cytoplasmic pH in control of mammalian target of rapamycin complex 1 (mTORC1) signaling","volume":"287","author":"Fonseca","year":"2012","journal-title":"J Biol Chem"},{"issue":"7","key":"10.1016\/j.bmcl.2019.03.032_b0095","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0159675","article-title":"Extracellular pH modulates neuroendocrine prostate cancer cell metabolism and susceptibility to the mitochondrial inhibitor niclosamide","volume":"11","author":"Ippolito","year":"2016","journal-title":"PLoS ONE"},{"issue":"9","key":"10.1016\/j.bmcl.2019.03.032_b0100","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pone.0007124","article-title":"Screen for chemical modulators of autophagy reveals novel therapeutic inhibitors of mTORC1 signaling","volume":"4","author":"Balgi","year":"2009","journal-title":"PLoS ONE"},{"issue":"9","key":"10.1016\/j.bmcl.2019.03.032_b0105","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1021\/ml100146z","article-title":"Identification of niclosamide as a new small-molecule inhibitor of the STAT3 signaling pathway","volume":"1","author":"Ren","year":"2010","journal-title":"ACS Med Chem Lett"},{"issue":"43","key":"10.1016\/j.bmcl.2019.03.032_b0110","doi-asserted-by":"crossref","first-page":"10267","DOI":"10.1021\/bi9009677","article-title":"The anti-helminthic niclosamide inhibits Wnt\/Frizzled1 signaling","volume":"48","author":"Chen","year":"2009","journal-title":"Biochemistry"},{"issue":"6","key":"10.1016\/j.bmcl.2019.03.032_b0115","doi-asserted-by":"crossref","first-page":"2516","DOI":"10.1158\/0008-5472.CAN-09-3950","article-title":"Antineoplastic mechanisms of niclosamide in acute myelogenous leukemia stem cells: inactivation of the NF-kappaB pathway and generation of reactive oxygen species","volume":"70","author":"Jin","year":"2010","journal-title":"Cancer Res"},{"issue":"4","key":"10.1016\/j.bmcl.2019.03.032_b0120","doi-asserted-by":"crossref","first-page":"682","DOI":"10.1002\/jcb.22065","article-title":"The autonomous notch signal pathway is activated by baicalin and baicalein but is suppressed by niclosamide in K562 cells","volume":"106","author":"Wang","year":"2009","journal-title":"J Cell Biochem"},{"key":"10.1016\/j.bmcl.2019.03.032_b0125","doi-asserted-by":"crossref","first-page":"1046","DOI":"10.1038\/cr.2017.88","article-title":"Existing drugs as broad-spectrum and potent inhibitors for Zika virus by targeting NS2B-NS3 interaction","volume":"27","author":"Li","year":"2017","journal-title":"Cell Res"},{"issue":"2","key":"10.1016\/j.bmcl.2019.03.032_b0130","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1021\/ml3003082","article-title":"Discovery of O-alkylamino tethered niclosamide derivatives as potent and orally bioavailable anticancer agents","volume":"4","author":"Chen","year":"2013","journal-title":"ACS Med Chem Lett"},{"key":"10.1016\/j.bmcl.2019.03.032_b0135","unstructured":"Spectra data of the representative compound: (S)-2-(2-Aminobutoxy)-5-chloro-N-(2-chloro-4-nitrophenyl)benzamide (8). Pale yellow solid. 1H NMR (600 MHz, DMSO-d6) \u03b4 8.51 (d, J\u202f=\u202f9.1\u202fHz, 1H), 8.43 (d, J\u202f=\u202f2.4\u202fHz, 1H), 8.28 (dd, J\u202f=\u202f9.1, 2.6\u202fHz, 1H), 7.92 (d, J\u202f=\u202f2.8\u202fHz, 1H), 7.64 (dd, J\u202f=\u202f8.9, 2.8\u202fHz, 1H), 7.38 (d, J\u202f=\u202f9.0\u202fHz, 1H), 4.24 (dd, J\u202f=\u202f10.2, 5.0\u202fHz, 1H), 4.06 (dd, J\u202f=\u202f10.1, 7.5\u202fHz, 1H), 3.02 (s, 1H), 1.56\u20131.48 (m, 1H), 1.32\u20131.26 (m, 1H), 0.91 (t, J\u202f=\u202f7.5\u202fHz, 3H). 13C NMR (150 MHz, DMSO-d6) \u03b4 162.7, 155.6, 143.3, 141.2, 133.4, 130.4, 125.1, 124.8, 124.5, 123.4, 123.3 (2C), 116.4, 74.8, 51.0, 26.5, 10.1. HRMS (ESI) calcd for C17H18Cl2N3O4 398.0674 (M\u202f+\u202fH)+, found 398.0670. HPLC analysis conditions: Waters \u03bcBondapak C18 (300\u202f \u00d7\u202f 3.9\u202fmm); flow rate 0.5\u202fmL\/min; UV detection at 270 and 254\u202fnm; linear gradient from 10% acetonitrile in water (0.1% TFA) to 100% acetonitrile (0.1% TFA) in 20\u202fmin followed by 30\u202fmin of the last-named solvent; tR\u202f=\u202f17.07 min; purity (by peak area) 96%."},{"issue":"10","key":"10.1016\/j.bmcl.2019.03.032_b0140","doi-asserted-by":"crossref","first-page":"5663","DOI":"10.1128\/AAC.00377-16","article-title":"Screening a commercial library of pharmacologically active small molecules against Staphylococcus aureus biofilms","volume":"60","author":"Torres","year":"2016","journal-title":"Antimicrob Agents Chemother."},{"key":"10.1016\/j.bmcl.2019.03.032_b0145","unstructured":"The activity screening studies were performed as follows: All compounds were screened at 15\u202f\u00b5g\/mL in 96-well plates to identify which produced inhibition of growth of the 16 clinical Enterobacteriaceae strains. Briefly, 50\u202f\u00b5L of 1\u202f\u00d7\u202f106 Colony Forming Unit (CFU) were inoculated in 50\u202f\u00b5L M\u00fceller Hinton Broth (MHB) medium in each well containing the different derivatives. Then, plates were incubated at 37\u202f\u00b0C with humidity for 18\u202fh. For each tested compound and strain, if after the incubation visual growth was observed in the wells the compound activity was considered negative. If no visual growth was observed in the wells the compound activity was considered positive. The screening was performed in duplicate."},{"key":"10.1016\/j.bmcl.2019.03.032_b0150","series-title":"Drug discovery and evaluation: safety and pharmacokinetic assays","first-page":"400","article-title":"Determination of solubility by hyphenated HPLC methods","author":"Vogel","year":"2006"},{"key":"10.1016\/j.bmcl.2019.03.032_b0155","doi-asserted-by":"crossref","first-page":"363","DOI":"10.3389\/fcimb.2018.00363","article-title":"In vitro activity of pentamidine alone and in combination with aminoglycosides, tigecycline, rifampicin, and doripenem against clinical strains of carbapenemase-producing and\/or colistin-resistant Enterobacteriaceae","volume":"8","author":"Cebrero-Cangueiro","year":"2018","journal-title":"Front Cell Infect Microbiol"},{"key":"10.1016\/j.bmcl.2019.03.032_b0160","unstructured":"For the determination of the Minimal Inhibitory Concentration (MIC) a broth microdilution method was used (cation-adjusted M\u00fceller Hinton broth; Becton Dickinson, Cockeysville, Md.), in accordance with the CLSI guidelines (Clinical and Laboratory Standards Institute, 2012). The compounds for which inhibition of the bacterial growth was observed in the screening studies were tested (6 clinical strains). The MIC value was the lowest concentration of derivative compound that completely inhibited the bacterial growth. All assays were performed in triplicate to ensure reproducibility."},{"issue":"12","key":"10.1016\/j.bmcl.2019.03.032_b0165","doi-asserted-by":"crossref","first-page":"1333","DOI":"10.1586\/14787210.2013.845523","article-title":"Combination therapy for carbapenem-resistant Gram-negative bacteria","volume":"11","author":"Zavascki","year":"2013","journal-title":"Expert Rev Anti Infect Ther"},{"issue":"4","key":"10.1016\/j.bmcl.2019.03.032_b0170","doi-asserted-by":"crossref","first-page":"2322","DOI":"10.1128\/AAC.02166-13","article-title":"Carbapenemase-producing Klebsiella pneumoniae bloodstream infections: lowering mortality by antibiotic combination schemes and the role of carbapenems","volume":"58","author":"Daikos","year":"2014","journal-title":"Antimicrob Agents Chemother"}],"container-title":["Bioorganic &amp; Medicinal Chemistry Letters"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960894X19301714?httpAccept=text\/xml","content-type":"text\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/api.elsevier.com\/content\/article\/PII:S0960894X19301714?httpAccept=text\/plain","content-type":"text\/plain","content-version":"vor","intended-application":"text-mining"}],"deposited":{"date-parts":[[2025,10,18]],"date-time":"2025-10-18T07:29:05Z","timestamp":1760772545000},"score":1,"resource":{"primary":{"URL":"https:\/\/linkinghub.elsevier.com\/retrieve\/pii\/S0960894X19301714"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6]]},"references-count":34,"journal-issue":{"issue":"11","published-print":{"date-parts":[[2019,6]]}},"alternative-id":["S0960894X19301714"],"URL":"https:\/\/doi.org\/10.1016\/j.bmcl.2019.03.032","relation":{},"ISSN":["0960-894X"],"issn-type":[{"value":"0960-894X","type":"print"}],"subject":[],"published":{"date-parts":[[2019,6]]},"assertion":[{"value":"Elsevier","name":"publisher","label":"This article is maintained by"},{"value":"Discovery of niclosamide and its O-alkylamino-tethered derivatives as potent antibacterial agents against carbapenemase-producing and\/or colistin resistant Enterobacteriaceae isolates","name":"articletitle","label":"Article Title"},{"value":"Bioorganic & Medicinal Chemistry Letters","name":"journaltitle","label":"Journal Title"},{"value":"https:\/\/doi.org\/10.1016\/j.bmcl.2019.03.032","name":"articlelink","label":"CrossRef DOI link to publisher maintained version"},{"value":"article","name":"content_type","label":"Content Type"},{"value":"\u00a9 2019 Elsevier Ltd. All rights reserved.","name":"copyright","label":"Copyright"}]}}