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The organ most implicated in chronic carriage and host transmission is the gallbladder due to bacterial biofilm formation on gallstones. Biofilms facilitate chronic infection because bacteria in biofilms are less susceptible to antibiotic treatment and immune factors in comparison to their planktonic brethren. Previously, we reported compounds that disrupt biofilms of\n                    <jats:italic>Salmonella enterica<\/jats:italic>\n                    serovar Typhimurium, a serovar closely related to\n                    <jats:italic>S<\/jats:italic>\n                    . Typhi, both in vitro and in vivo. This work extends the development of\n                    <jats:italic>Salmonella<\/jats:italic>\n                    antibiofilm agents through the further exploration of the parent scaffold. Lead antibiofilm compounds were tested for human ether\u2010a\u2010go\u2010go\u2010related gene (hERG) channel inhibition, from which we report new lead compounds with improved antibiofilm activity and reduced hERG channel inhibition.\n                  <\/jats:p>","DOI":"10.1002\/cmdc.70363","type":"journal-article","created":{"date-parts":[[2026,7,13]],"date-time":"2026-07-13T01:07:41Z","timestamp":1783904861000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Structure\u2013Activity Relationship Analysis and hERG Liability Assessment of Second\u2010Generation Antibiofilm Compounds Active Against\n                    <i>Salmonella<\/i>"],"prefix":"10.1002","volume":"21","author":[{"given":"Amy","family":"Sorge","sequence":"first","affiliation":[{"name":"Department of Chemistry and Biochemistry University of Notre Dame  Notre Dame Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aliyah N.","family":"Bennett","sequence":"additional","affiliation":[{"name":"Center for Microbe and Immunity Research Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital  Columbus Ohio USA"},{"name":"Infectious Diseases Institute The Ohio State University  Columbus Ohio USA"},{"name":"Department of Pediatrics College of Medicine The Ohio State University  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia E.","family":"Gregory","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of Notre Dame  Notre Dame Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Allysa L.","family":"Cole","sequence":"additional","affiliation":[{"name":"Center for Microbe and Immunity Research Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital  Columbus Ohio USA"},{"name":"Infectious Diseases Institute The Ohio State University  Columbus Ohio USA"},{"name":"Department of Pediatrics College of Medicine The Ohio State University  Columbus Ohio USA"},{"name":"Department of Veterinary Biosciences The Ohio State University  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katherine J.","family":"Woolard","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of Notre Dame  Notre Dame Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7249-5688","authenticated-orcid":false,"given":"Ansley M.","family":"Nemeth","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of Notre Dame  Notre Dame Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew H.","family":"Crow","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of Notre Dame  Notre Dame Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roberta J.","family":"Melander","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of Notre Dame  Notre Dame Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S.","family":"Gunn","sequence":"additional","affiliation":[{"name":"Center for Microbe and Immunity Research Abigail Wexner Research Institute at Nationwide Children\u2019s Hospital  Columbus Ohio USA"},{"name":"Infectious Diseases Institute The Ohio State University  Columbus Ohio USA"},{"name":"Department of Pediatrics College of Medicine The Ohio State University  Columbus Ohio USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8271-4696","authenticated-orcid":false,"given":"Christian","family":"Melander","sequence":"additional","affiliation":[{"name":"Department of Chemistry and Biochemistry University of Notre Dame  Notre Dame Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,7,12]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1473-3099(18)30685-6"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1136\/adc.75.3.214"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsomega.3c02386"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciz525"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pntd.0011168"},{"key":"e_1_2_8_7_1","first-page":"e00619","article-title":"Identification of a Host\u2010Targeted Compound to Control Typhoid Fever","volume":"10","author":"Hoang K. 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