{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:55:24Z","timestamp":1790844924463,"version":"4.1.0"},"reference-count":31,"publisher":"American Chemical Society (ACS)","issue":"12","license":[{"start":{"date-parts":[[2018,12,26]],"date-time":"2018-12-26T00:00:00Z","timestamp":1545782400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20GM103466"],"award-info":[{"award-number":["P20GM103466"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R15AI092315"],"award-info":[{"award-number":["R15AI092315"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2018,12,31]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>A series of novel chalcone and thiol-Michael addition analogues was synthesized and tested against Mycobacterium tuberculosis and other clinically significant bacterial pathogens. Previously reported chalcone-like antibacterials (1a\u2013c and 2) were used as a training set to generate a pharmacophore model. The chalcone derivative hit compound 3 was subsequently identified through a pharmacophore-based virtual screen of the Specs library of &amp;gt;200\u2009000 compounds. Among the newly synthesized chalcones and thiol-Michael addition analogues, chalcones 6r and 6s were active (minimum inhibitory concentrations (MICs) = 1.56\u20136.25 \u03bcg\/mL) against Gram-positive pathogens Bacillus anthracis and Staphylococcus aureus [methicillin-susceptible S. aureus (MSSA) and methicillin-resistant S. aureus (MRSA)]. The chalcone thiol-Michael addition derivatives 7j\u2013m showed good to excellent antibacterial activities (MICs = 0.78\u20136.25 \u03bcg\/mL) against Enterococcus faecalis, B. anthracis, and S. aureus. Interestingly, the amine-Michael addition analogue 12a showed promising anti-MRSA activity (MIC = 1.56 \u03bcg\/mL) with a selectivity index of 14 toward mammalian Vero cells. In addition, evaluation of selected compounds against biofilm and planktonic S. aureus (MSSA and MRSA) revealed that 12a exhibited bactericidal activities in these assays, which was overall superior to vancomycin. These properties may result from the compounds dissipating the proton motive force of bacterial membranes.<\/jats:p>","DOI":"10.1021\/acsomega.8b03174","type":"journal-article","created":{"date-parts":[[2018,12,26]],"date-time":"2018-12-26T15:00:27Z","timestamp":1545836427000},"page":"18343-18360","source":"Crossref","is-referenced-by-count":33,"title":["Pharmacophore Modeling, Synthesis, and Antibacterial Evaluation of\nChalcones and Derivatives"],"prefix":"10.1021","volume":"3","author":[{"given":"Mingming","family":"Zhang","sequence":"first","affiliation":[{"name":"University of Hawai\u2019i at Hilo , , 34 Rainbow Drive , , ,","place":["Hilo, Hawaii, United States, 96720"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5650-4644","authenticated-orcid":true,"given":"Allan M.","family":"Prior","sequence":"additional","affiliation":[{"name":"University of Hawai\u2019i at Hilo , , 34 Rainbow Drive , , ,","place":["Hilo, Hawaii, United States, 96720"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcus M.","family":"Maddox","sequence":"additional","affiliation":[{"name":"St. Jude Children\u2019s Research Hospital , , 262 Danny Thomas Place, MS#1000 , , ,","place":["Memphis, Tennessee, United States, 38105"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wan-Jou","family":"Shen","sequence":"additional","affiliation":[{"name":"Texas A&M Health Science Center , , 2121 West Holcombe Boulevard , , ,","place":["Houston, Texas, United States, 77030"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5584-3625","authenticated-orcid":true,"given":"Kirk E.","family":"Hevener","sequence":"additional","affiliation":[{"name":"University of Tennessee Health Science Center , , , ,","place":["Memphis, Tennessee, United States, 38163"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David F.","family":"Bruhn","sequence":"additional","affiliation":[{"name":"St. Jude Children\u2019s Research Hospital , , 262 Danny Thomas Place, MS#1000 , , ,","place":["Memphis, Tennessee, United States, 38105"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robin B.","family":"Lee","sequence":"additional","affiliation":[{"name":"St. Jude Children\u2019s Research Hospital , , 262 Danny Thomas Place, MS#1000 , , ,","place":["Memphis, Tennessee, United States, 38105"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aman P.","family":"Singh","sequence":"additional","affiliation":[{"name":"St. Jude Children\u2019s Research Hospital , , 262 Danny Thomas Place, MS#1000 , , ,","place":["Memphis, Tennessee, United States, 38105"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Justin","family":"Reinicke","sequence":"additional","affiliation":[{"name":"University of Hawai\u2019i at Hilo , , 34 Rainbow Drive , , ,","place":["Hilo, Hawaii, United States, 96720"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Charles J.","family":"Simmons","sequence":"additional","affiliation":[{"name":"University of Hawai\u2019i at Hilo , , , ,","place":["Hilo, Hawaii, United States, 96720"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2214-8105","authenticated-orcid":true,"given":"Julian G.","family":"Hurdle","sequence":"additional","affiliation":[{"name":"Texas A&M Health Science Center , , 2121 West Holcombe Boulevard , , ,","place":["Houston, Texas, United States, 77030"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard E.","family":"Lee","sequence":"additional","affiliation":[{"name":"St. Jude Children\u2019s Research Hospital , , 262 Danny Thomas Place, MS#1000 , , ,","place":["Memphis, Tennessee, United States, 38105"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7330-1742","authenticated-orcid":true,"given":"Dianqing","family":"Sun","sequence":"additional","affiliation":[{"name":"University of Hawai\u2019i at Hilo , , 34 Rainbow Drive , , ,","place":["Hilo, Hawaii, United States, 96720"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2018,12,26]]},"reference":[{"key":"2026090416083126900_cit1","doi-asserted-by":"publisher","first-page":"91","DOI":"10.1046\/j.1365-2796.2002.01026.x","article-title":"Evolution and spread of antibiotic resistance","volume":"252","author":"Normark","year":"2002","journal-title":"J. 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