In vitro and in vivo Activities of a New Lead Compound I2906 against Mycobacterium tuberculosisLu J. · Yue J. · Wu J. · Luo R. · Hu Z. · Li J. · Bai Y. · Tang Z. · Xian Q. · Zhang X. · Wang H.
aState Key Laboratory of Genetic Engineering, School of Life Science, Fudan University, bDepartment of Clinical Laboratory, Shanghai Pulmonary Hospital, Shanghai, cDepartment of Pathogenic Biology, School of Basic Medical Science, Tongji Medical College, Huazhong University of Science and Technology, and dWuhan University Center for Animal Experiment, Wuhan University, Wuhan, People’s Republic of China
Background: Due to the long duration of treatment and the emergence of multidrug-resistant strains, new antitubercular agents are urgently needed. I2906, as a novel lead, was screened and tested for efficacy in vitro and in vivo. Methods:To determine the efficacy of I2906,the minimum inhibitory concentrations against Mycobacterium tuberculosis and cytotoxicity were tested, and its in vivo activities were assessed by administering it to mice infected with M. tuberculosis H37Rv or multidrug-resistant strain. Results:Under in vitro conditions, I2906 showed excellent antimycobacterial activities and low cytotoxicity. In a murine model infected with M. tuberculosis H37Rv, the reductions on bacterial loads of both lungs and spleen were statistically significant (p < 0.05) between I2906-treated mice and untreated controls after 4 weeks. Further, the colony-forming unit counts in the lungs were dramatically lower (p < 0.05) than that of isoniazid-treated mice by the addition of I2906 after 8 weeks. Moreover, survival rate was increased by I2906 treatment. For multidrug-resistant strain infection, bacterial counts were reduced significantly in the lungs and spleen due to I2906 treatment in comparison with data from untreated controls (p < 0.05). Conclusions: I2906 displayed potential antimicrobial activities against M. tuberculosis H37Rv and drug-resistant strains in vitro and in vivo, and could improve efficacy of isoniazid in vivo.
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