{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,4]],"date-time":"2026-05-04T19:29:16Z","timestamp":1777922956683,"version":"3.51.4"},"reference-count":39,"publisher":"SAGE Publications","issue":"2","license":[{"start":{"date-parts":[[2020,2,1]],"date-time":"2020-02-01T00:00:00Z","timestamp":1580515200000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Microbial Drug Resistance"],"published-print":{"date-parts":[[2020,2]]},"abstract":"<jats:p>\n                    ZTW-41, an indolizinoquinoline-5,12-dione derivative, was investigated for antibacterial activity against Gram-positive bacteria, especially methicillin-resistant\n                    <jats:italic toggle=\"yes\">Staphylococcus aureus<\/jats:italic>\n                    (MRSA). In our study, the MIC\n                    <jats:sub>90<\/jats:sub>\n                    s (minimum inhibitory concentrations) of ZTW-41 against MRSA (MRSA,\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u2009200), methicillin-sensitive\n                    <jats:italic toggle=\"yes\">S. aureus<\/jats:italic>\n                    (MSSA,\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u2009100),\n                    <jats:italic toggle=\"yes\">Enterococcus faecalis<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">E. faecalis<\/jats:italic>\n                    ,\n                    <jats:italic toggle=\"yes\">n<\/jats:italic>\n                    \u2009=\u200932), and\n                    <jats:italic toggle=\"yes\">Enterococcus faecium<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">E. faecium n<\/jats:italic>\n                    \u2009=\u200932) were 0.25, 0.25, 0.125, and 8\u2009\u03bcg\/mL, respectively, whereas the MBC\n                    <jats:sub>90<\/jats:sub>\n                    s (minimum bactericidal concentrations) were 2, 1, 1, and &gt;32\u2009\u03bcg\/mL, respectively. ZTW-41 maintained its potency at different pH levels (range 5\u20139) and in starting inoculum size up to 10\n                    <jats:sup>7<\/jats:sup>\n                    CFU\/mL. The presence of human serum (25\u201375%) increased ZTW-41 MICs by two- to eightfold. Time-kill curves showed that ZTW-41 had bactericidal activity against MRSA, MSSA, and\n                    <jats:italic toggle=\"yes\">E. faecalis<\/jats:italic>\n                    strains within 8 hours, and rebound growth occurred after 8 hours except at higher multiples of the MIC (4\u2009\u00d7\u2009and 8\u2009\u00d7\u2009). In the acute toxicity study, no mortality or signs of toxicity was noted in mice after 14 days of observation at doses &lt;50\u2009mg\/kg. ZTW-41 exhibited good selectivity indices (SIs) (SI\u2009=\u2009IC\n                    <jats:sub>50<\/jats:sub>\n                    \/MIC\n                    <jats:sub>90<\/jats:sub>\n                    ) ranging from 1.12 to 71.76 against clinical isolates, demonstrating excellent therapeutic selectivity in MRSA, MSSA, and\n                    <jats:italic toggle=\"yes\">E. faecalis<\/jats:italic>\n                    strains. Moreover, the\n                    <jats:italic toggle=\"yes\">in vivo<\/jats:italic>\n                    efficacy (effective dose [ED]\n                    <jats:sub>50<\/jats:sub>\n                    \u2009=\u20096.59\u2009mg\/kg) of ZTW-41 was found comparable with vancomycin. Collectively, our favorable results supported ZTW-41 as a promising investigational candidate for treating drug-resistant bacteria infection.\n                  <\/jats:p>","DOI":"10.1089\/mdr.2019.0008","type":"journal-article","created":{"date-parts":[[2019,8,23]],"date-time":"2019-08-23T10:13:11Z","timestamp":1566555191000},"page":"100-109","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["ZTW-41, a Potent Indolizinoquinoline-5,12-Dione Derivative Against Drug-Resistant\n                    <i>Staphylococci<\/i>\n                    and\n                    <i>Enterococci<\/i>\n                    Bacteria"],"prefix":"10.1177","volume":"26","author":[{"given":"Chong-Fa","family":"Lai","sequence":"first","affiliation":[{"name":"Southern Medical University, Guangzhou, China."},{"name":"General Hospital of Southern Theatre Command, Guangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wei-Bin","family":"Xiao","sequence":"additional","affiliation":[{"name":"General Hospital of Southern Theatre Command, Guangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hua-Cheng","family":"Yan","sequence":"additional","affiliation":[{"name":"Center for Disease Control and Prevention of Southern Theatre Command, Guangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Yang","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lu-Xia","family":"Wang","sequence":"additional","affiliation":[{"name":"General Hospital of Southern Theatre Command, Guangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hui","family":"Guan","sequence":"additional","affiliation":[{"name":"General Hospital of Southern Theatre Command, Guangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiu-ju","family":"Peng","sequence":"additional","affiliation":[{"name":"Center for Disease Control and Prevention of Southern Theatre Command, Guangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi-Rong","family":"Deng","sequence":"additional","affiliation":[{"name":"Center for Disease Control and Prevention of Southern Theatre Command, Guangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jian-Wen","family":"Chen","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin-Kun","family":"An","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China."},{"name":"Guangdong Provincial Key Laboratory of New Drug Design and Evaluation, Guangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Shi","sequence":"additional","affiliation":[{"name":"Southern Medical University, Guangzhou, China."},{"name":"General Hospital of Southern Theatre Command, Guangzhou, China."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"179","published-online":{"date-parts":[[2020,2,3]]},"reference":[{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2014.2465"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1179\/2047773215Y.0000000030"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijid.2010.05.003"},{"key":"e_1_3_3_5_2","doi-asserted-by":"crossref","first-page":"563","DOI":"10.1016\/j.meegid.2013.04.030","article-title":"Evolution of community- and healthcare-associated methicillin-resistant Staphylococcus aureus","volume":"21","author":"Uhlemann A.C.","year":"2014","unstructured":"Uhlemann A.C., , Otto M., , Lowy F.D, , and DeLeo F.R.. 2014. 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