Skip to main content
NCBI home page
Antimicrobial Agents and Chemotherapy logoLink to Antimicrobial Agents and Chemotherapy
. 1995 Sep;39(9):2088–2091. doi: 10.1128/aac.39.9.2088

In vitro antimycobacterial activities of pyrazinamide analogs.

S Yamamoto 1, I Toida 1, N Watanabe 1, T Ura 1
PMCID: PMC162886  PMID: 8540721

Abstract

We synthesized various pyrazine derivatives and pyrazinamide analogs and assayed their antimycobacterial activities in vitro in order to find new drugs which are more active against Mycobacterium tuberculosis than pyrazinamide and also active against Mycobacterium avium and Mycobacterium intracellulare. Of the drugs synthesized, four drugs, namely, pyrazine thiocarboxamide, N-hydroxymethyl pyrazine thiocarboxamide, pyrazinoic acid n-octyl ester, and pyrazinoic acid pivaloyloxymethyl ester, were not only bacteriostatic but also bacteriocidal against these three species of mycobacteria in vitro under conditions in which pyrazinamide showed no or little activity. In conclusion, these four drugs are possible candidates for new antimycobacterial agents, and animal experiments are now under way.

Full Text

The Full Text of this article is available as a PDF (167.9 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Chin D. P. Mycobacterium avium complex and other nontuberculous mycobacterial infections in patients with HIV. Semin Respir Infect. 1993 Jun;8(2):124–138. [PubMed] [Google Scholar]
  2. DESSAU F. I., BURGER F., YEAGER R. L., KULISH M. A method for the determination of in vitro sensitivity of tubercle bacilli to pyrazinamide (aldinamide). Am Rev Tuberc. 1952 May;65(5):635–636. [PubMed] [Google Scholar]
  3. DESSAU F. I., YEAGER R. L., BURGER F. J., WILLIAMS J. H. Pyrazinamide (aldinamide) in experimental tuberculosis of the guinea pig. Am Rev Tuberc. 1952 May;65(5):519–522. [PubMed] [Google Scholar]
  4. Heifets L. B., Flory M. A., Lindholm-Levy P. J. Does pyrazinoic acid as an active moiety of pyrazinamide have specific activity against Mycobacterium tuberculosis? Antimicrob Agents Chemother. 1989 Aug;33(8):1252–1254. doi: 10.1128/aac.33.8.1252. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Horsburgh C. R., Jr Mycobacterium avium complex infection in the acquired immunodeficiency syndrome. N Engl J Med. 1991 May 9;324(19):1332–1338. doi: 10.1056/NEJM199105093241906. [DOI] [PubMed] [Google Scholar]
  6. Konno K., Feldmann F. M., McDermott W. Pyrazinamide susceptibility and amidase activity of tubercle bacilli. Am Rev Respir Dis. 1967 Mar;95(3):461–469. doi: 10.1164/arrd.1967.95.3.461. [DOI] [PubMed] [Google Scholar]
  7. MACKANESS G. B. The intracellular activation of pyrazinamide and nicotinamide. Am Rev Tuberc. 1956 Nov;74(5):718–728. doi: 10.1164/artpd.1956.74.5.718. [DOI] [PubMed] [Google Scholar]
  8. MALONE L., SCHURR A., LINDH H., McKENZIE D., KISER J. S., WILLIAMS J. H. The effect of pyrazinamide (aldinamide) on experimental tuberculosis in mice. Am Rev Tuberc. 1952 May;65(5):511–518. [PubMed] [Google Scholar]
  9. MCCUNE R. M., Jr, MCDERMOTT W., TOMPSETT R. The fate of Mycobacterium tuberculosis in mouse tissues as determined by the microbial enumeration technique. II. The conversion of tuberculous infection to the latent state by the administration of pyrazinamide and a companion drug. J Exp Med. 1956 Nov 1;104(5):763–802. doi: 10.1084/jem.104.5.763. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. McDERMOTT W., TOMPSETT R. Activation of pyrazinamide and nicotinamide in acidic environments in vitro. Am Rev Tuberc. 1954 Oct;70(4):748–754. doi: 10.1164/art.1954.70.4.748. [DOI] [PubMed] [Google Scholar]
  11. Salfinger M., Crowle A. J., Reller L. B. Pyrazinamide and pyrazinoic acid activity against tubercle bacilli in cultured human macrophages and in the BACTEC system. J Infect Dis. 1990 Jul;162(1):201–207. doi: 10.1093/infdis/162.1.201. [DOI] [PubMed] [Google Scholar]
  12. Salfinger M., Heifets L. B. Determination of pyrazinamide MICs for Mycobacterium tuberculosis at different pHs by the radiometric method. Antimicrob Agents Chemother. 1988 Jul;32(7):1002–1004. doi: 10.1128/aac.32.7.1002. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Steele M. A., Des Prez R. M. The role of pyrazinamide in tuberculosis chemotherapy. Chest. 1988 Oct;94(4):845–850. doi: 10.1378/chest.94.4.845. [DOI] [PubMed] [Google Scholar]
  14. YEAGER R. L., MUNROE W. G. C., DESSAU F. I. Pyrazinamide (aldinamide) in the treatment of pulmonary tuberculosis. Am Rev Tuberc. 1952 May;65(5):523–546. [PubMed] [Google Scholar]

Articles from Antimicrobial Agents and Chemotherapy are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES