{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:48:21Z","timestamp":1792003701353,"version":"4.4.0"},"reference-count":43,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T00:00:00Z","timestamp":1790467200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["ChemMedChem"],"published-print":{"date-parts":[[2026,10,14]]},"abstract":"<jats:p>\n                    Due to the lack of metallo\u2010\u03b2\u2010lactamase (M\u03b2L) inhibitors for clinical purposes, the antibiotic resistance mediated by M\u03b2L poses a clear threat to public health. In this work, twelve symmetrical\n                    <jats:italic>o<\/jats:italic>\n                    \u2010methylpyridine substituted tertiary amines\n                    <jats:bold>P1<\/jats:bold>\n                    \u2013\n                    <jats:bold>P6<\/jats:bold>\n                    and their Dy(III) complexes\n                    <jats:bold>D1<\/jats:bold>\n                    \u2013\n                    <jats:bold>D6<\/jats:bold>\n                    were synthesized, characterized, and confirmed. Nine compounds displayed inhibitory activity against M\u03b2Ls from subclasses B1, B2, and B3. Encouragingly,\n                    <jats:bold>D2<\/jats:bold>\n                    and\n                    <jats:bold>D6<\/jats:bold>\n                    exhibited dual inhibitory activity targeting both imipenem\u2010hydrolyzing M\u03b2L S (ImiS) and M\u03b2L L1 (L1). Mechanistic studies uncovered\n                    <jats:bold>P2<\/jats:bold>\n                    exerted a competitive inhibition mode on New Delhi M\u03b2L\u20101 (NDM\u20101), while\n                    <jats:bold>D6<\/jats:bold>\n                    showed a noncompetitive inhibition mode against ImiS and L1. Microbiological assays indicated the obtained inhibitors could restore the antibacterial activity of cefazolin and meropenem against six bacterial strains, including resistant ones, while\n                    <jats:bold>P4<\/jats:bold>\n                    ,\n                    <jats:bold>D1,<\/jats:bold>\n                    and\n                    <jats:bold>D6<\/jats:bold>\n                    alone exhibited bactericidal effect. Cytotoxicity assays showed the tested inhibitors performed a reasonable biological toxicity against L929 cells. Docking simulation reveals a molecular\u2010level rationale for the dual\u2010target inhibitory activity of\n                    <jats:bold>D2<\/jats:bold>\n                    , indicating the introduction of Dy(III) can regulate the inhibitory activity against both ImiS and L1. In short, the study demonstrate\n                    <jats:italic>o<\/jats:italic>\n                    \u2010methylpyridine substituted tertiary amines and their Dy(III) complexes are promising scaffolds for the development of M\u03b2Ls inhibitors and antibacterial agents.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70511","type":"journal-article","created":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T03:34:18Z","timestamp":1790566458000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Discovery of Symmetrical\n                    <i>o<\/i>\n                    \u2010Methylpyridine Substituted Tertiary Amines and Dy(III) Complexes as Metallo\u2010\u03b2\u2010Lactamase Inhibitor and Antimicrobial"],"prefix":"10.1002","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9632-8278","authenticated-orcid":false,"given":"Le","family":"Zhai","sequence":"first","affiliation":[{"name":"Shaanxi Key Laboratory of Phytochemistry College of Chemical and Materials Engineering Baoji University of Arts and Sciences  Baoji P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiazhu","family":"Chigan","sequence":"additional","affiliation":[{"name":"National Anti\u2010drug Laboratory Shaanxi Regional Center Anti\u2010Drug Technology Center of Shaanxi Provincial Public Security Department  Xi\u2019an P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-5140-3760","authenticated-orcid":false,"given":"Yao","family":"Zhao","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Phytochemistry College of Chemical and Materials Engineering Baoji University of Arts and Sciences  Baoji P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-4910-4380","authenticated-orcid":false,"given":"Hua\u2010Ping","family":"Xie","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Phytochemistry College of Chemical and Materials Engineering Baoji University of Arts and Sciences  Baoji P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi\u2010Qiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Shaanxi Key Laboratory of Phytochemistry College of Chemical and Materials Engineering Baoji University of Arts and Sciences  Baoji P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sheng","family":"Zhang","sequence":"additional","affiliation":[{"name":"School of Chemistry and Chemical Engineering Hainan University  Haikou P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2560-9659","authenticated-orcid":false,"given":"Ke\u2010Wu","family":"Yang","sequence":"additional","affiliation":[{"name":"Key Laboratory of Synthetic and Natural Functional Molecule Chemistry of Ministry of Education College of Chemistry and Materials Science Northwest University  Xi\u2019an P. R. China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,27]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(21)02724-0"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(24)01867-1"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmi.2016.09.003"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dki130"},{"key":"e_1_2_9_6_1","doi-asserted-by":"crossref","first-page":"a025239","DOI":"10.1101\/cshperspect.a025239","article-title":"\u03b2\u2010Lactamases: A Focus on Current Challenges","volume":"7","author":"Bonomo R. A.","year":"2016","journal-title":"Cold Spring Harbor Perspectives in Medicine"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1078\/1438-4221-00198"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.4236\/ajmb.2014.43011"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/jac\/dkaa392"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/cbic.202400280"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1080\/14787210.2018.1447381"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/s40265-023-01920-6"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.1c00138"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2021.113975"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2021.127956"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27227685"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2023.117559"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2023.116055"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2018.01.032"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.jmedchem.1c01755"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2021.105474"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.5b00495"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570180817999200831094019"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.201700182"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmc.2021.116128"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41429-021-00440-3"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2022.105928"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bioorg.2022.105910"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1080\/10426507.2016.1225741"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bmcl.2017.10.074"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsinfecdis.8b00137"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/jph.12603"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1002\/cmdc.202000123"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejmech.2019.01.083"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-018-02828-6"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1039\/D0DT02430A"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201509960"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.eng.2024.02.010"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41557-021-00831-x"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules27010056"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.cgd.2c00550"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.1021\/acs.inorgchem.0c02863"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.poly.2016.06.022"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mcat.2019.110498"}],"container-title":["ChemMedChem"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.70511","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cmdc.70511","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cmdc.70511","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T18:08:23Z","timestamp":1792001303000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/cmdc.70511"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,27]]},"references-count":43,"journal-issue":{"issue":"19","published-print":{"date-parts":[[2026,10,14]]}},"alternative-id":["10.1002\/cmdc.70511"],"URL":"https:\/\/doi.org\/10.1002\/cmdc.70511","archive":["Portico"],"relation":{},"ISSN":["1860-7179","1860-7187"],"issn-type":[{"value":"1860-7179","type":"print"},{"value":"1860-7187","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,27]]},"assertion":[{"value":"2026-05-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-10","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-27","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70511"}}