{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T22:52:58Z","timestamp":1773010378171,"version":"3.50.1"},"reference-count":39,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000060","name":"NIAID","doi-asserted-by":"publisher","award":["AI088025"],"award-info":[{"award-number":["AI088025"]}],"id":[{"id":"10.13039\/100000060","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"NIGMS","doi-asserted-by":"publisher","award":["GM119426"],"award-info":[{"award-number":["GM119426"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000062","name":"NIDDK","doi-asserted-by":"publisher","award":["DK136047"],"award-info":[{"award-number":["DK136047"]}],"id":[{"id":"10.13039\/100000062","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,2,25]]},"abstract":"<jats:p>\n                    One of the major mechanisms of resistance to ribosome\u2010targeting antibiotics is the modification of ribosomal RNA (rRNA). Specific methyltransferase enzymes, for example, confer high\u2010level resistance to aminoglycosides by selectively methylating the 16S rRNA in the ribosomal decoding center. These enzymes have been detected globally and pose a threat to the continued use of aminoglycosides. Compound\n                    <jats:bold>1<\/jats:bold>\n                    , a dehydroamino amide inhibitor of the m\n                    <jats:sup>1<\/jats:sup>\n                    A1408 methyltransferase NpmA, was previously disclosed and identified using high\u2010throughput virtual screening. Here, the synthesis and biological evaluation of rationally designed analogs of\n                    <jats:bold>1<\/jats:bold>\n                    has been reported. Guided by molecular docking, additional putative inhibitors of NpmA, as well as the functionally related m\n                    <jats:sup>7<\/jats:sup>\n                    G1405 methyltransferase RmtB, varying in each region of the original scaffold are disclosed. A modular, fragment\u2010based synthesis enables access to 17 analogs, which exhibits mixed activity against NpmA and RmtB, including several that are selective for RmtB. The structure\u2013activity relationship determined for the dehydroamino amide series will guide continued research against this target class with the aim of developing a toolkit for selective\u2010 or pan\u201016S rRNA methyltransferase inhibition.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.202500889","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T01:50:20Z","timestamp":1765245020000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Design, Synthesis, and Evaluation of Novel Inhibitors of Aminoglycoside\u2010Resistance 16S Ribosomal RNA Methyltransferases"],"prefix":"10.1002","volume":"21","author":[{"given":"Benjamin E.","family":"Deprez","sequence":"first","affiliation":[{"name":"Department of Chemistry Emory University  Atlanta Georgia 30322 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Debayan","family":"Dey","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Emory University School of Medicine  Atlanta Georgia 30322 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Natalia","family":"Zelinskaya","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Emory University School of Medicine  Atlanta Georgia 30322 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Erika E.","family":"Csatary","sequence":"additional","affiliation":[{"name":"Department of Chemistry Emory University  Atlanta Georgia 30322 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qimin Winnie","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Chemistry Emory University  Atlanta Georgia 30322 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Minhua","family":"Nie","sequence":"additional","affiliation":[{"name":"Department of Chemistry Emory University  Atlanta Georgia 30322 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2419-380X","authenticated-orcid":false,"given":"Graeme L.","family":"Conn","sequence":"additional","affiliation":[{"name":"Department of Biochemistry Emory University School of Medicine  Atlanta Georgia 30322 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5198-7744","authenticated-orcid":false,"given":"William M.","family":"Wuest","sequence":"additional","affiliation":[{"name":"Department of Chemistry Emory University  Atlanta Georgia 30322 USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)01867-1"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abl5997"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/978-3-319-46718-4_14"},{"key":"e_1_2_9_5_1","first-page":"a027029","volume-title":"Cold Spring Harb Perspect Med","author":"Krause K. 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