title: Synthesis, antimycobacterial and antibacterial evaluation of l-[(1R, 2S)-2-fluorocyclopropyl]fluoroquinolone derivatives containing an oxime functional moiety.
abstract: A series of novel 1-[(1R, 2S)-2-fluorocyclopropyl]fluoroquinolone derivatives 9a-d containing an oxime functional moiety were synthesized and evaluated for their biological activity. Our results reveal that 9a1 and 9b3 have good in vitro activity against MTB H37Rv ATCC 27294 (MIC: 0.25 μg/mL) and two MDR-MTB clinical isolates (MICs: 0.065-0.125 μg/mL). Most of 9a-d show potent activity against Escherichia coli and Klebsiella pneumoniae (MICs: <0.008-4 μg/mL) except extended-spectrum β-lactamase-producing strains. Especially, 9a1 and 9d4 possessing excellent in vitro activity against all of the fourteen Gram-positive strains including MRSA and MRSE (MICs: <0.008-2 μg/mL) comparable to or better than the four reference drugs, show considerable in vivo efficacy against five Gram-negative and Gram-positive isolate strains (ED50s: 11.43-26.04 mg/kg).
authors.affiliation: New Drug Research & Development Center, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China.
authors.forename: Hongmin
authors.initials: H
authors.lastname: Liu
authors.affiliation: New Drug Research & Development Center, School of Pharmaceutical Sciences, Zhengzhou University, Zhengzhou 450001, China; 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: Department of Cardiac Surgery, Beijing An Zhen Hospital, Capital Medical University, Beijing 100029, China.
authors.forename: Jiayang
authors.initials: J
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. Electronic address: lmllyx@126.com.
authors.forename: Mingliang
authors.initials: M
authors.lastname: Liu
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: Huiyuan
authors.initials: H
authors.lastname: Guo
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* / Q000737:chemistry / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D024841:Fluoroquinolones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D010091:Oximes / Q000737:chemistry*; D013329:Structure-Activity Relationship
chemical_list: C000598946:1-((1R, 2S)-2-fluorocyclopropyl)fluoroquinolone; D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D010091:Oximes
keywords: Antibacterial activity; Antimycobacterial activity; Fluoroquinolone derivatives; Synthesis