{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T08:40:13Z","timestamp":1790844013537,"version":"4.1.0"},"reference-count":37,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2022,3,23]],"date-time":"2022-03-23T00:00:00Z","timestamp":1647993600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82173688"],"award-info":[{"award-number":["82173688"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the science and technology innovation Program of Hunan Province","award":["2021RC4067"],"award-info":[{"award-number":["2021RC4067"]}]},{"name":"Hunan Provincial Natural Science Foundation of China","award":["2021JJ30791"],"award-info":[{"award-number":["2021JJ30791"]}]},{"name":"the Chinese Ministry of Education 111 Project","award":["BP0820034"],"award-info":[{"award-number":["BP0820034"]}]},{"name":"the Fundamental Research Funds for the Central Universities of Central South University","award":["2018zzts240"],"award-info":[{"award-number":["2018zzts240"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Antibiotics"],"abstract":"<jats:p>Type II fatty acid synthases are promising drug targets against major bacterial pathogens. Platensimycin (PTM) is a potent inhibitor against \u03b2-ketoacyl-[acyl carrier protein] synthase II (FabF) and \u03b2-ketoacyl-[acyl carrier protein] synthase I (FabB), while the poor pharmacokinetics has prevented its further development. In this work, thirty-two PTM derivatives were rapidly prepared via Heck, Sonogashira, and one-pot Sonogashira\/cycloaddition cascade reactions based on the Gram-scale synthesis of 6-iodo PTM (4). About half of the synthesized compounds were approximately equipotent to PTM against the tested Staphylococcus aureus strains. Among them, the representative compounds 4, A4, and B8 exhibited different plasma protein binding affinity or stability in the human hepatic microsome assay and showed improved in vivo efficacy over PTM in a mouse peritonitis model. In addition, A4 was also effective in an S. aureus-infected skin mouse model. Our study not only significantly expands the known PTM derivatives with improved antibacterial activities in vivo, but showcased that C\u2013C cross-coupling reactions are useful tools to functionalize natural product drug leads.<\/jats:p>","DOI":"10.3390\/antibiotics11040425","type":"journal-article","created":{"date-parts":[[2022,3,22]],"date-time":"2022-03-22T23:30:23Z","timestamp":1647991823000},"page":"425","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Morphing Natural Product Platensimycin via Heck, Sonogashira, and One-Pot Sonogashira\/Cycloaddition Reactions to Produce Antibiotics with In Vivo Activity"],"prefix":"10.3390","volume":"11","author":[{"given":"Youchao","family":"Deng","sequence":"first","affiliation":[{"name":"Xiangya International Academy of Translational Medicine, Central South University, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuling","family":"Li","sequence":"additional","affiliation":[{"name":"Xiangya International Academy of Translational Medicine, Central South University, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhongqing","family":"Wen","sequence":"additional","affiliation":[{"name":"Xiangya International Academy of Translational Medicine, Central South University, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claudia H.","family":"Ruiz","sequence":"additional","affiliation":[{"name":"Departments of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiang","family":"Weng","sequence":"additional","affiliation":[{"name":"Xiangya International Academy of Translational Medicine, Central South University, Changsha 410013, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael D.","family":"Cameron","sequence":"additional","affiliation":[{"name":"Departments of Molecular Medicine, The Scripps Research Institute, Jupiter, FL 33458, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanwen","family":"Duan","sequence":"additional","affiliation":[{"name":"Xiangya International Academy of Translational Medicine, Central South University, Changsha 410013, China"},{"name":"Hunan Engineering Research Center of Combinatorial Biosynthesis and Natural Product Drug Discovery, Changsha 410011, China"},{"name":"National Engineering Research Center of Combinatorial Biosynthesis for Drug Discovery, Changsha 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3163-1716","authenticated-orcid":false,"given":"Yong","family":"Huang","sequence":"additional","affiliation":[{"name":"Xiangya International Academy of Translational Medicine, Central South University, Changsha 410013, China"},{"name":"National Engineering Research Center of Combinatorial Biosynthesis for Drug Discovery, Changsha 410011, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,23]]},"reference":[{"key":"ref_1","unstructured":"World Health Organiztion (2022, February 12). 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