title: Synthesis, antimycobacterial and antibacterial activity of l-[(1R,2S)-2-fluorocyclopropyl]naphthyridone derivatives containing an oxime-functionalized pyrrolidine moiety.
abstract: A series of novel 1-[(1R,2S)-2-fluorocyclopropyl]naphthyridone derivatives 21-24 containing an oxime-functionalized pyrrolidine moiety were designed, synthesized and evaluated for their biological activity. Our results reveal that compounds 21a, 21e and 21j show considerable activity against MTB H37Rv ATCC 27294 (MICs: <0.25 μg/mL) and MDR-MTB 6133 (MICs: 0.03-0.054 μg/mL). The target compounds 21-24 are generally poor against the Gram-negative strains, but 21a-j and 22a-c have potent potency (MICs: <0.008-32 μg/mL) against all of the tested Gram-positive strains including MRSA and MRSE with a few exceptions, and the most active compounds 21d, 21e and 22a-c (MICs: <0.008-32 μg/mL) were found to be comparable to or better than moxifloxacin, and 2->250 times more potent than ciprofloxacin and levofloxacin.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Ju
authors.initials: J
authors.lastname: Huang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; Department of Pharmacy, Hebei General Hospital, Hebei, Shijiazhuang 050051, China.
authors.forename: Hongtao
authors.initials: H
authors.lastname: Liu
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China. Electronic address: lmllyx@126.com.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Liu
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Linhu
authors.initials: L
authors.lastname: Li
authors.affiliation: Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Department of Pharmacology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing 101149, China.
authors.forename: Bin
authors.initials: B
authors.lastname: Wang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Minghua
authors.initials: M
authors.lastname: Wang
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
authors.forename: Chunlan
authors.initials: C
authors.lastname: Wang
authors.affiliation: Beijing Key Laboratory of Drug Resistance Tuberculosis Research, Department of Pharmacology, Beijing Tuberculosis and Thoracic Tumor Research Institute, Beijing Chest Hospital, Capital Medical University, Beijing 101149, China. Electronic address: luyu4876@hotmail.com.
authors.forename: Yu
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology; D024901:Drug Resistance, Multiple, Bacterial; D024841:Fluoroquinolones / Q000494:pharmacology; D006090:Gram-Negative Bacteria / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D064704:Levofloxacin / Q000494:pharmacology; D000077266:Moxifloxacin; D009287:Naphthyridines / Q000138:chemical synthesis / Q000494:pharmacology*; D010091:Oximes / Q000138:chemical synthesis / Q000494:pharmacology*; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000494:pharmacology*; D013237:Stereoisomerism
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; D010091:Oximes; D011759:Pyrrolidines; D002939:Ciprofloxacin; D064704:Levofloxacin; D000077266:Moxifloxacin
keywords: Antibacterial activity; Antimycobacterial activity; Fluoroquinolone derivatives; Synthesis