{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T22:31:15Z","timestamp":1788993075687,"version":"build-2803163510"},"reference-count":21,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,7,18]],"date-time":"2018-07-18T00:00:00Z","timestamp":1531872000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"High Point University (High Point, NC)"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chem Biol Drug Des"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Methicillin\u2010resistant <jats:italic>Staphylococcus aureus<\/jats:italic> (<jats:styled-content style=\"fixed-case\">MRSA<\/jats:styled-content>) is the leading cause of recurrent infections in humans including endocarditis, pneumonia, and toxic shock syndrome. Novel therapeutics to treat <jats:styled-content style=\"fixed-case\">MRSA<\/jats:styled-content> and other resistant bacteria are urgently needed. Adjuvant therapy, which uses a non\u2010toxic compound to repotentiate the toxic effects of an existing antibiotic, is an attractive response to the growing resistance crisis. Herein, we describe the evaluation of structurally related, <jats:styled-content style=\"fixed-case\">FDA<\/jats:styled-content>\u2010approved tricyclic amine antidepressants that selectively repotentiate <jats:styled-content style=\"fixed-case\">MRSA<\/jats:styled-content> to \u03b2\u2010lactam antibiotics. Our results identify important structural features of the tricyclic amine class for \u03b2\u2010lactam adjuvant activity. Furthermore, we describe the mechanism of action for our lead compound, amoxapine, and illustrate that it represses the <jats:styled-content style=\"fixed-case\">mRNA<\/jats:styled-content> levels of key \u03b2\u2010lactam resistance genes in response to \u03b2\u2010lactam treatment. This work is novel in that it highlights an important class of small molecules with the ability to simultaneously inhibit production of both \u03b2\u2010lactamase and penicillin binding protein 2a.<\/jats:p>","DOI":"10.1111\/cbdd.13361","type":"journal-article","created":{"date-parts":[[2018,6,28]],"date-time":"2018-06-28T18:29:46Z","timestamp":1530210586000},"page":"1822-1829","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":19,"title":["Tricyclic amine antidepressants suppress \u03b2\u2010lactam resistance in methicillin\u2010resistant <i>Staphylococcus aureus<\/i> (<scp>MRSA<\/scp>) by repressing <scp>mRNA<\/scp> levels of key resistance genes"],"prefix":"10.1111","volume":"92","author":[{"given":"Kyra","family":"Gillard","sequence":"first","affiliation":[{"name":"Department of Chemistry High Point University  High Point North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1400-7716","authenticated-orcid":false,"given":"Heather B.","family":"Miller","sequence":"additional","affiliation":[{"name":"Department of Chemistry High Point University  High Point North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9632-0567","authenticated-orcid":false,"given":"Meghan S.","family":"Blackledge","sequence":"additional","affiliation":[{"name":"Department of Chemistry High Point University  High Point North Carolina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,7,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.coph.2014.09.006"},{"key":"e_1_2_8_3_1","unstructured":"C. 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