{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,13]],"date-time":"2025-10-13T00:24:08Z","timestamp":1760315048038,"version":"build-2065373602"},"reference-count":30,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2018,9,14]],"date-time":"2018-09-14T00:00:00Z","timestamp":1536883200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["252810"],"award-info":[{"award-number":["252810"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemBioChem"],"published-print":{"date-parts":[[2018,10,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Aminoglycosides are a group of broad\u2010spectrum antibiotics that have been used in the clinic for almost a century. The rapid spread of bacterial genes coding for aminoglycoside\u2010modifying enzymes has, however, dramatically decreased the utility of aminoglycosides. We have previously reported several aminoglycoside potentiators that work by inhibiting aminoglycoside <jats:italic>N<\/jats:italic>\u20106\u2032\u2010acetyltransferase, one of the most common determinants of aminoglycoside resistance. Among these, prodrugs that combine the structure of an aminoglycoside with that of pantothenate into one molecule are especially promising. We report here a series of cellular studies to investigate the activity and mechanism of action of these prodrugs further. Our results reveal a new aminoglycoside resistance inhibitor, as well as the possibility that these prodrugs are transformed into more than one inhibitor in bacteria. We also report that the onset of the potentiators is rapid. Their low cell cytotoxicity, good stability, and potentiation of various aminoglycosides, against both Gram\u2010positive and Gram\u2010negative bacteria, make them interesting compounds for the development of new drugs.<\/jats:p>","DOI":"10.1002\/cbic.201800368","type":"journal-article","created":{"date-parts":[[2018,7,30]],"date-time":"2018-07-30T12:48:23Z","timestamp":1532954903000},"page":"2107-2113","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Cellular Studies of an Aminoglycoside Potentiator Reveal a New Inhibitor of Aminoglycoside Resistance"],"prefix":"10.1002","volume":"19","author":[{"given":"Jinming","family":"Guan","sequence":"first","affiliation":[{"name":"Department of Chemistry McGill University  801 Sherbrooke Street West Montreal Quebec H3A 0B8 Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kenward","family":"Vong","sequence":"additional","affiliation":[{"name":"Department of Chemistry McGill University  801 Sherbrooke Street West Montreal Quebec H3A 0B8 Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathleen","family":"Wee","sequence":"additional","affiliation":[{"name":"Target Validation Division The Centre for Drug Research and Development  2405 Westbrook Mall, 4th Floor Vancouver British Columbia V6T 1Z3 Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johans","family":"Fakhoury","sequence":"additional","affiliation":[{"name":"Department of Chemistry McGill University  801 Sherbrooke Street West Montreal Quebec H3A 0B8 Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Edie","family":"Dullaghan","sequence":"additional","affiliation":[{"name":"Target Validation Division The Centre for Drug Research and Development  2405 Westbrook Mall, 4th Floor Vancouver British Columbia V6T 1Z3 Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0933-7956","authenticated-orcid":false,"given":"Karine","family":"Auclair","sequence":"additional","affiliation":[{"name":"Department of Chemistry McGill University  801 Sherbrooke Street West Montreal Quebec H3A 0B8 Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2018,9,14]]},"reference":[{"key":"e_1_2_6_1_1","doi-asserted-by":"publisher","DOI":"10.1021\/cb3005116"},{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/ja.2017.117"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23020284"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.drup.2010.08.003"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.4155\/fmc.13.80"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1086\/313949"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.200501399"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/ange.200501399"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1021\/jm060732n"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2007.02.009"},{"key":"e_1_2_6_10_1","doi-asserted-by":"publisher","DOI":"10.1021\/bi701957c"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2008.09.004"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.200802172"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1039\/c0ob01018a"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201100346"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1021\/cb200366u"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M403152200"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1006\/jmbi.2001.5272"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/prot.20541"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.42.7.1842"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1136\/thx.2009.131532"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.2165\/11597020-000000000-00000"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1086\/381972"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1086\/514620"},{"key":"e_1_2_6_24_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1574-6976.2007.00093.x"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1042\/BST20140131"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.201600078"},{"key":"e_1_2_6_27_1","first-page":"277","volume":"40","author":"Ventola C. 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