title: Synthesis and antibacterial activity of amino acid and dipeptide prodrugs of IMB-070593, a fluoroquinolone candidate.
abstract: A series of amino acid and dipeptide prodrugs of IMB-070593, a fluoroquinolone candidate discovered in our lab, were synthesized and evaluated for their water solubility and then antibacterial activity. Our results reveal that four amino acid prodrugs 4a,b,e,f and two dipeptide prodrugs 4k,l have much greater solubility (>85 mg/mL) than IMB-070593 mesylate (22.5 mg/mL). Compounds 4a and 4k show good in vivo efficacy against MSSA 12-1 (p.o./i.v., 5.32-7.68 mg/kg) and S. pneumoniae12-10 (p.o., 18.39-23.13 mg/kg) which is 1.19-1.50 fold more active than the parent drug.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Zhejiang Starry Pharmaceutical Co. Ltd., Xianju 317300, China.
authors.forename: Jinwei
authors.initials: J
authors.lastname: Wu
authors.affiliation: Zhejiang Starry Pharmaceutical Co. Ltd., Xianju 317300, China.
authors.forename: Shihong
authors.initials: S
authors.lastname: Chen
authors.affiliation: China Resources Double-Crane Pharmaceutical Co. Ltd., Beijing 100102, China.
authors.forename: Kaixiang
authors.initials: K
authors.lastname: Liu
authors.affiliation: Harbin Stomatological Hospital, Harbin 150010, China.
authors.forename: Yabin
authors.initials: Y
authors.lastname: Lin
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Huiyuan
authors.initials: H
authors.lastname: Guo
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. lmllyx@126.com.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Liu
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D060326:Chemistry Techniques, Synthetic; D004151:Dipeptides / Q000737:chemistry* / Q000494:pharmacology*; D007275:Injections, Intravenous; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects; D051379:Mice; D008826:Microbial Sensitivity Tests; D010091:Oximes / Q000737:chemistry*; D010880:Piperidines / Q000737:chemistry*; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D012995:Solubility
chemical_list: D000900:Anti-Bacterial Agents; D004151:Dipeptides; C583739:IMB-070593; D010091:Oximes; D010880:Piperidines; D011355:Prodrugs