A novel benzothiazinethione analogue SKLB-TB1001 displays potent antimycobacterial activities in a series of murine models

• Published in: Biomedicine & pharmacotherapy Vol. 88; pp. 603 - 609
• Main Authors: Gao, Chao, Ye, Ting-Hong, Peng, Cui-Ting, Shi, Yao-jie, You, Xin-Yu, Xiong, Lu, Ran, Kai, Zhang, Li-Dan, Zeng, Xiu-Xiu, Wang, Ning-Yu, Yu, Luo-Ting, Wei, Yu-Quan
• Format: Journal Article
• Language: English
• Published: France Elsevier Masson SAS 01.04.2017
• Subjects: Animals; Antitubercular Agents - pharmacology; Colony Count, Microbial; Disease Models, Animal; Female; H37Rv; Internal Medicine; Lung - drug effects; Lung - microbiology; Lung - pathology; MDR-TB; Medical Education; Mice, Inbred BALB C; Mice, Inbred C57BL; Murine models; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; SKLB-TB1001; Survival Analysis; Thiadiazoles - chemical synthesis; Thiadiazoles - chemistry; Thiadiazoles - pharmacology; Thiadiazoles - therapeutic use; Treatment Outcome; Tuberculosis - drug therapy; Tuberculosis - microbiology; Tuberculosis - pathology; INH; bacillus Calmette-Guérin; SAR; colony-forming units; multidrug-resistant; totally drug-resistant; CFU; DprE1/DprE2; ABL3; Decaprenylphosphoryl-β- d-ribose 2′-epimerasethe; MDR; SM; structure-activity relationship; H37Rv; WHO; TDR; isoniazid; Streptomycin; World Health Organization; tuberculosis; XDR; BCG; MDR-TB; TB; Mycobacterium tuberculosis; Murine models; extensively drug-resistant; Animal Biosafty Level III; SKLB-TB1001
• ISSN: 0753-3322; 1950-6007
• DOI: 10.1016/j.biopha.2017.01.098

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.