title: Synthesis, antimycobacterial and antibacterial activity of fluoroquinolone derivatives containing an 3-alkoxyimino-4-(cyclopropylanimo)methylpyrrolidine moiety.
abstract: A series of novel fluoroquinolone derivatives containing an 3-alkoxyimino-4-(cyclopropylanimo)methylpyrrolidine moiety were designed, synthesized and evaluated for their biological activity. Our results revealed that 19b2 shows good activity against MTB H37Rv ATCC 27294 (MIC: <0.25 μg/mL) and MDR-MTB 6133 clinical isolate (MIC: 0.11 μg/mL). Most of them have potent potency against Gram-positive strains, although they are generally poor active against Gram-negative strains. Especially, compounds 22b1 and 23a3 (MICs: <0.008-8 μg/mL) were found to 2-128 times more potent than ciprofloxacin and levofloxacin against all of the tested Gram-positive strains including quinolone-resistant MRSA, MRSE, Enterococcus faecium and Enterococcus faecalis.
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China; Zhejiang Starry Pharmaceutical Co. Ltd., Xianju 317300, China.
authors.forename: Tingting
authors.initials: T
authors.lastname: Zhang
authors.affiliation: Zhejiang Starry Pharmaceutical Co. Ltd., Xianju 317300, China.
authors.forename: Weiyi
authors.initials: W
authors.lastname: Shen
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: 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: 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: 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*; D004305:Dose-Response Relationship, Drug; D016983:Enterococcus / Q000187:drug effects*; D024841:Fluoroquinolones / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D011759:Pyrrolidines / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy
chemical_list: D000900:Anti-Bacterial Agents; D024841:Fluoroquinolones; D011759:Pyrrolidines
keywords: Antibacterial activity; Antimycobacterial activity; Fluoroquinolone derivatives; Synthesis