Browsing by Author "Yang, Lu"

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    Design, synthesis and antitubercular evaluation of benzothiazinones containing a piperidine moiety
    (Elsevier, 2018-05) Lv, Kai; Tao, Zeyu; Liu, Qian; Yang, Lu; Wang, Bin; Wu, Shuo; Wang, Apeng; Huang, Menghao; Liu, Mingliang; Lu, Yu; Medicine, School of Medicine
    We herein report the design and synthesis of benzothiazinones containing a piperidine moiety as new antitubercular agents based on the structure feature of IMB-ZR-1 discovered in our lab. Some of them were found to have good in vitro activity (MIC < 1 μg/mL) against drug-susceptible Mycobacterium tuberculosis H37RV strain. After two set of modifications, compound 2i were found to display comparable in vitro anti-TB activity (MIC < 0.016 μg/mL) to PBTZ169 against drug-sensitive and resistant mycobacterium tuberculosis strains. Compound 2i also showed acceptable PK profiles. Studies to determine PK profiles in lung and in vivo efficacy of 2i are currently under way.
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    Identification of benzothiazones containing a hexahydropyrrolo[3,4- c]pyrrol moiety as antitubercular agents against MDR-MTB
    (Royal Society of Chemistry, 2020-04-07) Ma, Xican; Han, Bing; Wang, Aoyu; Yang, Lu; Huang, Menghao; Chowdhury, Kushan; Gu, Jian; Zhang, Kai; Lv, Kai; Biochemistry and Molecular Biology, School of Medicine
    IMB1603, a spiro-benzothiazone compound discovered by our lab, displayed potent anti-MTB activity in vitro and in vivo. In this study, we reported a series of new BTZs containing the hexahydropyrrolo[3,4-c]pyrrol moiety based on the structure of IMB1603. Among them, BTZs 11 and 24 displayed potent anti-MTB (MIC < 0.035 μM) and MDR-MTB (MIC, 0.053-0.102 μM) activity, good solubility (1.82-1.85 μg mL-1), and low cytotoxicity (CC50 > 200 μM), suggesting BTZs 11 and 24 may serve as promising candidates for further study. The molecular docking study of 11 toward DprE was also investigated, and revealed that 11 mimicked the binding pattern of PBTZ169 in the active site of DprE1.