Sulfa antibacterials and arylpyrimidine antifolates

  • Scott L. Dax


The discovery and development of the sulfonamide antibacterial agents in many ways ushered in the modern era of antibacterial chemotherapy. The preceding decades were rich in advances in chemical technology (i.e. synthesis) and in the understanding of many disease processes. At the turn of the century, infectious disease research was evolving from a passive study based primarily upon the power of observation, to a science in which bacterial species could be identified, cultured and examined. The fundamental processes of pathogenesis were recognized and could even be anticipated in some instances. However, prior to the pioneering work of Paul Ehrlich, scientists were essentially incapable of conceiving and designing biologically active substances. Most often chance prevailed and significant advances were slow to come.


Antibacterial Agent Dihydrofolate Reductase Sulfonamide Resistance Sulfonamide Agent Benzenesulfonyl Chloride 
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Further reading

  1. N. Anand(1975) ‘Sulfonamides and sulfones’ in Antibiotics III (Mechanism of Action of Antimicrobial and Antitumor Agents) J.W. Concoran and F.E. Hahn (Eds), Springer-Verlag, New York, pp. 668–698.Google Scholar
  2. J.J.Burchall(1975) ‘Trimethoprim and pyrimethamine’ in Antibiotics III (Mechanism of Action of Antimicrobial and Antitumor Agents) J.W. Concoran and F.E. Hahn (Eds), Springer-Verlag, New York, pp. 304–320.Google Scholar
  3. F.M. Sirotnak, J.J. Burchall, W.B. Erisminger and J.A. Montgomery (Eds) (1984)Folate Antagonists as Therapeutic Agents; Vol. I Biochemistry, Molecular Actions and Synthetic Design Academic Press, Orlando, FL.Google Scholar
  4. G.H. Hitching (Ed.) (1983) ‘Inhibition of folate metabolism in chemotherapy, the origins and uses of co-trimoxazole’,Handbook of Experimental Pharmacology Vol. 64, Springer-Verlag, Germany.Google Scholar
  5. E.H. Northey (1948)The Sulfonamides and Allied Compounds American Chemical Society Monograph Series, Reinhold, New York.Google Scholar
  6. J.K. Seydel (1968) ‘Sulfonamides, Structure-Activity Relationship, and Mode of Action’,J.Pharm. Sei.571455.Google Scholar
  7. M. Kansy, J.K. Seydel, M. Wiese and R. Haller (1992) ‘Synthesis of new 2,4—diamino—5—benzylpyrimidines active against bacterial species’,Eur. J. Med. Chem.27 237.CrossRefGoogle Scholar
  8. J.H. Chan and B. Roth (1991) ‘2,4-Diamino-5-benzylpyrimidines as antibacterial agents. 14. 2,3—Dihydro—l—(2,4—diamino—5—pyrimidyl)-lH-indenes as conformationally restricted analogues of trimethoprim’,J. Med. Chem.34 550.CrossRefGoogle Scholar
  9. J.J. Burchall, L.P. Elwell and M.E. Fling (1982) ‘Molecular Mechanisms of Resistance to Trimethoprim’,Rev. Infectious Diseases 4 246.CrossRefGoogle Scholar
  10. P. Huovinen (1989) ‘Trimethoprim Resistance’,Antimicrob. Agents Chemother.31 1451.Google Scholar
  11. M.L, Pato and G.M. Brown (1963) ‘Mechanisms of resistance ofEscherichia colito Sulfonamides’,Arch. Biochem. Biophys.103443.CrossRefGoogle Scholar
  12. P.J. Ortiz (1970) ‘Dihydrofolate and dihydropteroate synthesis by partially purified enzymes from wild-type and sulfonamide-resistant pneumococcus’,Biochemistry 9 355.CrossRefGoogle Scholar
  13. P.J. White and D.D. Woods (1965) ‘The synthesis of p-aminobenzoic acid and folic acid by staphyl sensitive and resistant to sulphonamides’,J. Gen. Microbiol.40 255.Google Scholar
  14. B. Wolf and R.D. Hotchkiss (1963) ‘Genetically modified folic acid synthesizing enzymes of Pneumococcus’,Biochemistry 2, 145–150.CrossRefGoogle Scholar
  15. E.M. Wise, Jr. and M.M. Abou-Donia (1975) ‘Sulfonamide resistance mechanism inEscherichia coli: R plasmids can determine sulfonamide-resistant dihydropteroate synthases’,Proc. Natl. Acad. Sei. USA 722621.CrossRefGoogle Scholar
  16. G. Swedberg, S. Castensson and O. Skold (1979) ‘Characterization of mutationally altered dihydropteroate synthase and its ability to form a sulfonamide-containing dihydrofolate analog’,J. Bacteriol 137 129.Google Scholar
  17. O. Skold (1976) ‘R—factor—mediated resistance to sulfonamides by a plasmid-borne, drug-resistant dihydropteroate synthase’,Antimicrobial Agents Chemother.9 49.Google Scholar
  18. L. Bock, G.H. Miller, K.-J. Schaper and J.K. Seydel (1974) ‘Sulfonamide structure-activity relationships in a cell-free system. 2. Proof for the formation of a sulfonamide-containing folate analog’,J. Med. Chem.1723.CrossRefGoogle Scholar
  19. G.E. Dale, R.L. Then and D. Stuber (1993) Characterization of the Gene for Chromosomal Trimethopro Sensitive Dihydrofolate Reductase ofStaphylococcus aureusATCC, 25923,Antimicrobial Agents Chemother.371400–1405.Google Scholar
  20. K.H. Mayer, M.E. Fling, J.D. Hopkins and T.F. O’Brien (1985) ‘Trimethoprim resistance in multiple genera of enterobacteriaceae at a US hospital: spread of type II dihydrofolate reductase gene by a single plasmid’,J. Infectious Diseases 151783.CrossRefGoogle Scholar
  21. L. Sundstrom, T. Vinayagamoorthy and O. Skold (1987) ‘Novel type of plasmid-borne resistance to trimethoprim’,Antimicrobial Agents Chemother.31 60.Google Scholar
  22. R. Steen and O. Skold (1985) ‘Plasmid-borne or chromosomally mediated resistance by Tn7 is the most common response to ubiquitous use of trimethoprim’,Antimicrobial Agents Chemother.27933–937.Google Scholar

Copyright information

© Chapman & Hall 1997

Authors and Affiliations

  • Scott L. Dax
    • 1
  1. 1.Research InstituteThe R.W Johnson PharmaceuticalSpring HouseUSA

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