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Vol. 85, No. 6, 2010
Issue release date: July 2010

In vitro and in vivo Activities of a New Lead Compound I2906 against Mycobacterium tuberculosis

Lu J. · Yue J. · Wu J. · Luo R. · Hu Z. · Li J. · Bai Y. · Tang Z. · Xian Q. · Zhang X. · Wang H.
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Abstract

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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Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in goverment regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
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References

  1. Global Alliance for TB Drug Development: Developing a faster TB cure. 2004; www.tballiance.org.
  2. O’Brien RJ, Nunn PP: The need for new drugs against tuberculosis. Am J Respir Crit Care Med 2001;163:1055–1058.
  3. Centers for Disease Control and Prevention (CDC): Plan to combat extensively drug-resistant tuberculosis: recommendations of the Federal Tuberculosis Task Force. MMWR Recomm Rep 2009;58:1–43.
  4. Bentrup KHZ, Miczak A, Swenson DL, Russell DG: Characterization of activity and expression of isocitrate lyase in Mycobacterium avium and Mycobacterium tuberculosis. J Bacteriol 1999;181:7161–7167.
  5. Sharma V, Sharma S, Bentrup KHZ, Mckinney JD, Russell DG, Jacobs JWR, Sacchettini JC: Structure of isocitrate lyase, a persistence factor of mycobacterium tuberculosis. Nat Struct Biol 2000;7:663–668.
  6. Bai B, Xie JP, Yan JF, Wang HH, Hu CH: A high throughput screening approach to identify isocitrate lyase inhibitors from traditional Chinese medicine sources. Drug Dev Res 2006;67:818–823.
  7. Falzari K, Zhu ZH, Pan DH, Liu HW, Hongmanee P, Franzblau SG: In vitro and in vivo activities of macrolide derivatives against Mycobacterium tuberculosis. Antimicrob Agents Chemother 2005;49:1447–1454.
  8. Shen HB, Wang FF, Zhang Y, Huang Q, Xu SF, Hu HR, Yue J, Wang HH: A novel inhibitor of indole-3-glycerol phosphate synthase with activity against multidrug-resistant Mycobacterium tuberculosis. FEBS J 2009;276:144–154.
  9. Siddiqi SH, Libonati JP, Middlebrook G: Evaluation of rapid radiometric method for drug susceptibility testing of Mycobacterium tuberculosis. J Clin Microbiol 1981;13:908–912.
  10. Kradolfer F: Rifampicin, isoniazid, ethambutol, ethionamide, and streptomycin in murine tuberculosis: comparative chemotherapeutic studies. Antibiot Chemother (Basel) 1970;16:352–360.
  11. Ji BH, Lounis N, Maslo C, Truffot-Pernot C, Bonnafous P, Grosset J: In vitro and in vivo activities of moxifloxacin and clinafloxacin against Mycobacterium tuberculosis. Antimicrob Agents Chemother 1998;42:2066–2069.
  12. Oleksijew A, Meulbroek J, Ewing P, Jarvis K, Mitten M, Paige L, Tovcimak A, Nukkula M, Chu D, Alder JD: In vivo efficacy of ABT-255 against drug-sensitive and -resistant Mycobacterium tuberculosis strains. Antimicrob Agents Chemother 1998;42:2674–2677.


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