{"entity": "publication", "iuid": "b4bebb95f7e84dae8edc5c1683d20632", "timestamp": "2026-08-29T04:16:06.335Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/b4bebb95f7e84dae8edc5c1683d20632.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/b4bebb95f7e84dae8edc5c1683d20632"}}, "title": "Discovery of novel triphenylphosphonium conjugated pleuromutilin with enhanced anti-MRSA effect and broaden antibacterial spectrum.", "authors": [{"family": "Feng", "given": "Bo", "initials": "B"}, {"family": "Hu", "given": "Huabin", "initials": "H"}, {"family": "Xiang", "given": "Jin", "initials": "J"}, {"family": "Wu", "given": "Guangxu", "initials": "G"}, {"family": "Zhu", "given": "Zihao", "initials": "Z"}, {"family": "Zhang", "given": "Gao", "initials": "G"}, {"family": "Zhang", "given": "Jie", "initials": "J"}, {"family": "Pan", "given": "Weidong", "initials": "W"}, {"family": "Zhang", "given": "Wenxuan", "initials": "W"}, {"family": "Li", "given": "Tianlei", "initials": "T"}, {"family": "Wu", "given": "Song", "initials": "S"}], "type": "journal article", "published": "2025-09-15", "journal": {"title": "Eur J Med Chem", "issn": "1768-3254", "volume": "294", "pages": "117731", "issn-l": "0223-5234"}, "abstract": "Pleuromutilin, a diterpene fungal metabolite, serves as a privileged scaffold for antibiotic discovery. Improving its antibacterial activity and broadening its spectrum remain the primary objectives in developing novel pleuromutilin derivatives. To obtain an ideal candidate, a series of pleuromutilin analogues conjugated to the triphenylphosphonium cation (TPP+) were designed and synthesized. Among them, compound a5 demonstrated enhanced anti-MRSA potency and a broadened antibacterial spectrum compared to valnemulin and lefamulin, both in vitro and in vivo. Mechanistic studies revealed that a5 disrupted bacterial membranes and biofilms by elevating intracellular ROS levels-a mechanism distincts from conventional pleuromutilins, which primarily target ribosomal proteins. These findings position a5 as a promising lead compound for developing next-generation broad-spectrum antibacterial agents.", "doi": "10.1016/j.ejmech.2025.117731", "pmid": "40398156", "labels": [], "xrefs": [{"db": "pii", "key": "S0223-5234(25)00496-9"}], "notes": [], "created": "2026-08-21T11:18:41.860Z", "modified": "2026-08-21T11:18:41.874Z"}