{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T14:38:11Z","timestamp":1786977491765,"version":"build-2736575974"},"reference-count":54,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2014,7,23]],"date-time":"2014-07-23T00:00:00Z","timestamp":1406073600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2014,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Semisynthetic derivatives of the clinically useful aminoglycosides tobramycin and amikacin were prepared by selectively modifying their 6\u2032\u2032 positions with a variety of hydrogen bond donors and acceptors. Their binding to the rRNA A\u2010site was probed using an in vitro FRET\u2010based assay, and their antibacterial activities against several resistant strains (e.g.,\n                    <jats:italic>Pseudomonas aeruginosa<\/jats:italic>\n                    ,\n                    <jats:italic>Klebsiella pneumonia<\/jats:italic>\n                    , MRSA) were quantified by determining minimum inhibitory concentrations (MICs). The most potent derivatives were evaluated for their eukaryotic cytotoxicity. Most analogues displayed higher affinity for the bacterial A\u2010site than the parent compounds. Although most tobramycin analogues exhibited no improvement in antibacterial activity, several amikacin analogues showed potent and broad\u2010spectrum antibacterial activity against resistant bacteria. Derivatives tested for eukaryotic cytotoxicity exhibited minimal toxicity, similar to the parent compounds.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.201402175","type":"journal-article","created":{"date-parts":[[2014,7,23]],"date-time":"2014-07-23T15:48:02Z","timestamp":1406130482000},"page":"2164-2171","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":20,"title":["Singly Modified Amikacin and Tobramycin Derivatives Show Increased rRNA A\u2010Site Binding and Higher Potency against Resistant Bacteria"],"prefix":"10.1002","volume":"9","author":[{"given":"Richard J.","family":"Fair","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lisa S.","family":"McCoy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mary E.","family":"Hensler","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernice","family":"Aguilar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Nizet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yitzhak","family":"Tor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2014,7,23]]},"reference":[{"key":"e_1_2_7_1_2","doi-asserted-by":"publisher","DOI":"10.1155\/2006\/707296"},{"key":"e_1_2_7_2_2","unstructured":"\u00a0"},{"key":"e_1_2_7_3_2","doi-asserted-by":"publisher","DOI":"10.1098\/rstb.2009.0037"},{"key":"e_1_2_7_4_2","doi-asserted-by":"publisher","DOI":"10.1128\/MMBR.00016-10"},{"key":"e_1_2_7_5_2","unstructured":"\u00a0"},{"key":"e_1_2_7_6_2","doi-asserted-by":"publisher","DOI":"10.1086\/533452"},{"key":"e_1_2_7_7_2","doi-asserted-by":"publisher","DOI":"10.1086\/595011"},{"key":"e_1_2_7_8_2","doi-asserted-by":"publisher","DOI":"10.1586\/eri.13.12"},{"key":"e_1_2_7_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.01169-07"},{"key":"e_1_2_7_10_2","unstructured":"\u00a0"},{"key":"e_1_2_7_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/cit152"},{"key":"e_1_2_7_12_2","doi-asserted-by":"publisher","DOI":"10.1086\/420937"},{"key":"e_1_2_7_13_2","unstructured":"\u00a0"},{"key":"e_1_2_7_14_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200200528"},{"key":"e_1_2_7_14_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200200528"},{"key":"e_1_2_7_15_2","doi-asserted-by":"publisher","DOI":"10.1086\/383472"},{"key":"e_1_2_7_16_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1106753"},{"key":"e_1_2_7_17_2","doi-asserted-by":"publisher","DOI":"10.1586\/eri.11.53"},{"key":"e_1_2_7_18_2","unstructured":"\u00a0"},{"key":"e_1_2_7_19_2","doi-asserted-by":"publisher","DOI":"10.1586\/14787210.6.5.593"},{"key":"e_1_2_7_20_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-007-7034-x"},{"key":"e_1_2_7_21_2","doi-asserted-by":"publisher","DOI":"10.1086\/429323"},{"key":"e_1_2_7_22_2","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.201300496"},{"key":"e_1_2_7_23_2","unstructured":"\u00a0"},{"key":"e_1_2_7_24_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1445-5994.2011.02452.x"},{"key":"e_1_2_7_25_2","doi-asserted-by":"publisher","DOI":"10.1097\/QCO.0000000000000012"},{"key":"e_1_2_7_26_2","unstructured":"\u00a0"},{"key":"e_1_2_7_27_2","doi-asserted-by":"publisher","DOI":"10.1038\/327389a0"},{"key":"e_1_2_7_28_2","doi-asserted-by":"publisher","DOI":"10.1038\/35030019"},{"key":"e_1_2_7_29_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.1060612"},{"key":"e_1_2_7_30_2","doi-asserted-by":"publisher","DOI":"10.1002\/wrna.60"},{"key":"e_1_2_7_31_2","doi-asserted-by":"publisher","DOI":"10.1021\/cb3005116"},{"key":"e_1_2_7_32_2","unstructured":"For recent examples of synthetic and semisynthetic aminoglycoside analogues see:"},{"key":"e_1_2_7_33_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2010.03.116"},{"key":"e_1_2_7_34_2","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201200761"},{"key":"e_1_2_7_34_3","doi-asserted-by":"publisher","DOI":"10.1002\/ange.201200761"},{"key":"e_1_2_7_35_2","doi-asserted-by":"publisher","DOI":"10.1021\/ol4030138"},{"key":"e_1_2_7_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.carres.2013.02.003"},{"key":"e_1_2_7_37_2","doi-asserted-by":"publisher","DOI":"10.1021\/jo302247x"},{"key":"e_1_2_7_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2013.12.125"},{"key":"e_1_2_7_39_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.533588"},{"key":"e_1_2_7_40_2","unstructured":"\u00a0"},{"key":"e_1_2_7_41_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1074-5521(02)00153-9"},{"key":"e_1_2_7_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.biochi.2006.05.017"},{"key":"e_1_2_7_43_2","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201200150"},{"key":"e_1_2_7_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0968-0896(99)00071-1"},{"key":"e_1_2_7_45_2","unstructured":"\u00a0"},{"key":"e_1_2_7_46_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja905767g"},{"key":"e_1_2_7_47_2","doi-asserted-by":"publisher","DOI":"10.1039\/c0cc00423e"},{"key":"e_1_2_7_48_2","doi-asserted-by":"publisher","DOI":"10.7164\/antibiotics.25.695"},{"key":"e_1_2_7_49_2","doi-asserted-by":"publisher","DOI":"10.1021\/ja056159z"},{"key":"e_1_2_7_50_2","doi-asserted-by":"publisher","DOI":"10.1021\/jm049696n"},{"key":"e_1_2_7_51_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2958.2002.03132.x"},{"key":"e_1_2_7_52_2","unstructured":"Performance Standards for Antimicrobial Susceptibility Testing 19th Informational Supplement M100\u2010S19 Clinical and Laboratory Standards Institute Wayne PA USA 2008."}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcmdc.201402175","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.201402175","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T10:02:46Z","timestamp":1760263366000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.201402175"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,7,23]]},"references-count":54,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2014,9]]}},"alternative-id":["10.1002\/cmdc.201402175"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.201402175","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,7,23]]},"assertion":[{"value":"2014-05-03","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2014-07-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}