Correlations between Structure and Antimycobacterial Activity in a Series of 2-Acetylpyridine Thiosemicarbazones Free

Abstract

The antimycobacterial activity of a new series of 2-acetylpyridine thiosemicarbazones was determined using ATCC 607. The resulting log minimal inhibitory concentration (μmol l) values were plotted against the partition coefficient (log ) values for each compound, and fell on a parabolic distribution curve having a log of 3.0. Compounds having partition coefficients outside the range 2.0 to 4.0 were inactive against . When similar assays were carried out using and , a similar series of parabolic activity curves were obtained having log values around 4.0. The significance of this shift in the log value obtained using the slow-growing pathogenic mycobacteria compared to that observed with the rapid-growing is discussed in relation to the structures of the variable substituents of these new 2-acetylpyridine thiosemicarbazone compounds.

Loading

Article metrics loading...

/content/journal/micro/10.1099/00221287-128-6-1349
1982-06-01
2024-03-28
Loading full text...

Full text loading...

/deliver/fulltext/micro/128/6/mic-128-6-1349.html?itemId=/content/journal/micro/10.1099/00221287-128-6-1349&mimeType=html&fmt=ahah

References

  1. Behnisch R., Mletzsch r., Schmidt H. 1950; Chemical studies on thiosemicarbazones with particular reference to antituberculous activity. American Review of Tuberculosis 61:1–7
    [Google Scholar]
  2. Brown R. E., Stancata F. A., Wolfe A. D. 1981; Preferential inhibition of ribonucleic acid synthesis by a new thiosemicarbazone possessing antibacterial and antiparasitic properties. Antimicrobial Agents and Chemotherapy 19:234–237
    [Google Scholar]
  3. Dobek A. S., Klayman D. L., Dickson E. T., Scovill J. P., Tramont E. C. 1980; Inhibition of clinically significant bacterial organisms in vitro by 2-acetylpyridine thiosemicarbazones. Antimicrobial Agents and Chemotherapy 18:27–36
    [Google Scholar]
  4. Domagk G. 1950; Investigations on the antituberculous activity of the thiosemicarbazones in vitro and in vivo . American Review of Tuberculosis 61:8–19
    [Google Scholar]
  5. Fujita T., Hansch C. 1967; Analysis of the structure-activity relationships of the sulfonamide drugs using substituent constants. Journal of Medicinal Chemistry 10:991–1000
    [Google Scholar]
  6. Goren M. B. 1972; Mycobacterial lipids: selected topics. Bacteriological Reviews 36:33–64
    [Google Scholar]
  7. Hansch C., Leo A. J. 1979 Substituent Constants for Correlation Analysis in Chemistry and Biology New York: Wiley Interscience;
    [Google Scholar]
  8. Hansch D., Lien E. J., Helmer F. 1968; Structure-activity correlations in the metabolism of drugs. Archives of Biochemistry and Biophysics 128:319–330
    [Google Scholar]
  9. Klayman D. L., Bartosevich J. F., Mason C. J., Scovill J. P. 1979a; 2-Acetylpyridine thiosemicarbazones. 1. A new class of potential antimalarial agents. Journal of Medicinal Chemistry 22:855–883
    [Google Scholar]
  10. Klayman D. L., Scovill J. P., Bartosevich J. F., Mason C. J. 1979b; 2-Acetylpyridine thiosemicarbazones. 2. N4,N4-disubstituted derivatives as potential antimalarial agents. Journal of Medicinal Chemistry 22:1367–1373
    [Google Scholar]
  11. Leo A., Hansch C., Elkins D. 1971; Partition coefficients and their uses. Chemical Reviews 71:525–616
    [Google Scholar]
  12. Lien E. J., Hansch C. 1968; Correlation of rates of drug metabolism by microsomal fractions with partition coefficients. Journal of Pharmaceutical Science 57:1027–1028
    [Google Scholar]
  13. Lowe J. 1954; The chemotherapy of leprosy. Late results of treatment with sulfone and with thiosemicarbazones. Lancet 2:1064–1068
    [Google Scholar]
  14. Martin Y. C. 1978 Quantitative Drug Design New York: Marcel Dekker;
    [Google Scholar]
  15. Morrison N. E. 1971; Sequential blockade of the mycobacterial de novo folate pathway. International Journal of Leprosy 39:34–43
    [Google Scholar]
  16. Morrison N. E., Collins F. M. 1981; Antimycobacterial activity of 2-acetylpyridine thiosemicarbazones in relation to their antileprosy activity. International Journal of Leprosy 49:180–186
    [Google Scholar]
  17. Tute M. S. 1971; Principles and practice of Hansch analysis: a guide to structure-activity correlations for the medicinal chemist. Advances in Drug Research 6:1–77
    [Google Scholar]
  18. Wolinsky E. 1979; Nontuberculous mycobacteria and associated disease. American Review of Respiratory Diseases 119:107–159
    [Google Scholar]
  19. Zar J. H. 1974 Biostatistical Analysis New York: Prentice-Hall;
    [Google Scholar]
http://instance.metastore.ingenta.com/content/journal/micro/10.1099/00221287-128-6-1349
Loading
/content/journal/micro/10.1099/00221287-128-6-1349
Loading

Data & Media loading...

Most cited Most Cited RSS feed