title: 3H-1,2,4-Dithiazol-3-one compounds as novel potential affordable antitubercular agents.
abstract: Small molecules with oxathiazol-2-one moiety were recently reported as potent inhibitors of Mycobacterium bovis var. bacilli Calmette-Guérin (BCG), among which HT1171 was the most potent and selective proteasome inhibitor. Herein we synthesized a series of novel compounds by bioisosteric replacement of the oxathiazol-2-one ring with 3H-1,2,4-dithiazol-3-one, and also fifteen 1,3,4-oxathiazol-2-one molecules in order for potency comparison and structure-activity relationship elucidation since their antibacterial effects on the virulent strains were not evaluated before. All the compounds were assessed for antitubercular activities on the virulent H37Rv strain by a serial dilution method. Among the tested compounds, 3H-1,2,4-dithiazol-3-one compound 4n was found to be the most active with a lowest MIC(90) value of 1 μg/mL. Furthermore, the cytotoxicities of all the compounds against normal human liver cell line L02 were determined by an MTT method. Compound 4n displayed a lower inhibitory ratio than HT1171 at the concentration of 100 μM, indicating its better safety profile.
authors: State Key Laboratory of Biotherapy, West China Hospital, West China Medical School, Sichuan University, Chengdu, Sichuan 610041, PR China.
authors: Jianzhong
authors: J
authors: Yang
authors: Weiyi
authors: W
authors: Pi
authors: Li
authors: L
authors: Xiong
authors: Wei
authors: W
authors: Ang
authors: Tao
authors: T
authors: Yang
authors: Jun
authors: J
authors: He
authors: Yuanyuan
authors: Y
authors: Liu
authors: Ying
authors: Y
authors: Chang
authors: Weiwei
authors: W
authors: Ye
authors: Zhenling
authors: Z
authors: Wang
authors: Youfu
authors: Y
authors: Luo
authors: Yuquan
authors: Y
authors: Wei
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology / Q000633:toxicity; D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D006801:Humans; D008099:Liver / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000737:chemistry* / Q000494:pharmacology* / Q000633:toxicity
chemical_list: D000900:Anti-Bacterial Agents; D000995:Antitubercular Agents; D013844:Thiazoles