title: A novel benzothiazinethione analogue SKLB-TB1001 displays potent antimycobacterial activities in a series of murine models.
abstract: New chemotherapeutic compounds and regimens are needed to combat multidrug-resistant Mycobacterium tuberculosis. Here, we used a series of murine models to assess an antitubercular lead compound SKLB-TB1001. In the Mycobacterium bovis bacillus Calmette-Guérin and the acute M. tuberculosis H37Rv infection mouse models, SKLB-TB1001 significantly attenuated the mycobacterial load in lungs and spleens. The colony forming unit counts and histological examination of lungs from H37Rv infected mice revealed that the benzothiazinethione analogue SKLB-TB1001 as a higher dose level was as effective as isoniazid. Moreover, in a multidrug-resistant (MDR)-TB mouse model, SKLB-TB1001 showed significant activity in a dose-dependent manner and was more effective than streptomycin. These results suggested that SKLB-TB1001 could be an antitubercular drug candidate worth further investigation.
authors.affiliation: Department of Liver Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University/Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, PR China.
authors.forename: Chao
authors.initials: C
authors.lastname: Gao
authors.affiliation: Department of Liver Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University/Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, PR China. Electronic address: yeth1309@scu.edu.cn.
authors.forename: Ting-Hong
authors.initials: TH
authors.lastname: Ye
authors.affiliation: Department of Liver Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University/Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, PR China; Department of Pharmaceutical and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu, Sichuan 610065, PR China.
authors.forename: Cui-Ting
authors.initials: CT
authors.lastname: Peng
authors.affiliation: Department of Liver Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University/Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, PR China.
authors.forename: Yao-Jie
authors.initials: YJ
authors.lastname: Shi
authors.affiliation: Department of Liver Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University/Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, PR China; Department of Pharmaceutical and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu, Sichuan 610065, PR China.
authors.forename: Xin-Yu
authors.initials: XY
authors.lastname: You
authors.affiliation: Department of Liver Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University/Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, PR China.
authors.forename: Lu
authors.initials: L
authors.lastname: Xiong
authors.affiliation: Department of Liver Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University/Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, PR China.
authors.forename: Kai
authors.initials: K
authors.lastname: Ran
authors.affiliation: Department of Liver Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University/Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, PR China; Department of Pharmaceutical and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu, Sichuan 610065, PR China.
authors.forename: Li-Dan
authors.initials: LD
authors.lastname: Zhang
authors.affiliation: Department of Pharmaceutical and Bioengineering, School of Chemical Engineering, Sichuan University, Chengdu, Sichuan 610065, PR China.
authors.forename: Xiu-Xiu
authors.initials: XX
authors.lastname: Zeng
authors.affiliation: Department of Liver Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University/Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, PR China.
authors.forename: Ning-Yu
authors.initials: NY
authors.lastname: Wang
authors.affiliation: Department of Liver Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University/Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, PR China. Electronic address: yuluot@scu.edu.cn.
authors.forename: Luo-Ting
authors.initials: LT
authors.lastname: Yu
authors.affiliation: Department of Liver Surgery, State Key Laboratory of Biotherapy, West China Hospital, Sichuan University/Collaborative Innovation Center for Biotherapy, Chengdu, Sichuan 610041, PR China.
authors.forename: Yu-Quan
authors.initials: YQ
authors.lastname: Wei
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000494:pharmacology*; D015169:Colony Count, Microbial; D004195:Disease Models, Animal; D005260:Female; D008168:Lung / Q000187:drug effects / Q000382:microbiology / Q000473:pathology; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D016019:Survival Analysis; D013830:Thiadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D016896:Treatment Outcome; D014376:Tuberculosis / Q000188:drug therapy / Q000382:microbiology / Q000473:pathology
chemical_list: D000995:Antitubercular Agents; D013830:Thiadiazoles
keywords: H37Rv; MDR-TB; Murine models; Mycobacterium tuberculosis; SKLB-TB1001