Advertisement

Physicochemical Factors in Drug-Receptor Interactions Demonstrated on the Example of the Sulfanilamides

  • Joachim K. Seydel
Part of the Topics in Infectious Diseases book series (TIDIS, volume 1)

Abstract

At the beginning of my lecture I would like to make the following statement: The relation between physicochemical parameters in a homologous series of biologically active compounds and the exerted biological response can quantitatively be described by suitable mathematical and statistical treatment of the data. I hope that during my lecture I can convince you that this statement holds. It seems obvious that we can expect very close relations between the chemicals used as a drug and the biological system which acts as a receptor. Both consist of molecules. The interactions between the chemical substance and the biological systems are responsible for the effect in the organism. The reactions of enzymes or receptor systems obey the law of mass action, even if we do not yet fully understand how. If we can explore the type of interaction between the drug molecule and the receptor molecules of the target cells then we can understand the mechanism of action on a molecular level.

Keywords

Minimal Inhibition Concentration Physicochemical Parameter Sulfanilic Acid Single Point Method Folate Synthesis 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. BELL, P.H., and R.O. ROBLIN: A theory of the relation of structure to activity of sulfanilamide type compounds. J. Am. Chem. Soc. 64, 2905–2917 (1942).CrossRefGoogle Scholar
  2. BOCK, L., G.H. MILLER, K.J. SCHAPER, and J.K. SEYDEL: Sulfonamide structure-activity relationship in a cell-free system. II Proof for the formation of a sulfonamide containing folate analogue. J. Med. Chem. 17, 23–28 (1974).PubMedCrossRefGoogle Scholar
  3. BROWN, G.M.: The biosynthesis of folic acid. II Inhibition by sulfonamides. J. Biol. Chem. 237, 536–540 (1962).PubMedGoogle Scholar
  4. BROWN, G.M.: Methods for measuring inhibition by sulfonamides of the enzymatic synthesis of dihydropteroic acid. Methods Med. Res. 10, 233–238 (1964).Google Scholar
  5. BRUECKNER, A.H.: Sulfonamide activity as influenced by variation in pH of culture media. Yale J. Biol. Med. 15, 813–821 (1943).Google Scholar
  6. COWLES, P.B.: The possible role of ionization in the bacteriostatic action of the sulfonamides. Yale J. Biol. Med. 14, 599–604 (1942).Google Scholar
  7. CRAIG, P.N.: Interdependence between physical parameters and selection of substituent groups for correlation studies. J. Med. Chem. 14, 680–684 (1971).PubMedCrossRefGoogle Scholar
  8. CRAIG, P.N., C.H. HANSCH, J.W.McFARLAND, Y.C.MARTIN, W.P. PURCELL, and R. ZAHRADNIK: Minimal statistical data for structure-function correlations. J. Med. Chem. 14, 447 (1971).PubMedCrossRefGoogle Scholar
  9. FUJITA, T., J. IWASA, and C. HANSCH: A new substituent constant, fr, derived from partition coefficients, J. Am. Chem. Soc. 86, 5175–5180 (1964).CrossRefGoogle Scholar
  10. JAENICKE, L., and P.C. CHAN: Die Biosynthese der Folsäure. Angew. Chem. 72, 752–753 (1960).Google Scholar
  11. McCULLOUGH, J.L., and T.H. MAREN: Inhibition of dihydropteroate synthetase from Escherichia coli by sulfones and sulfonamides. Antimicrob. Agents Chemother. 3, 665–669 (1973).Google Scholar
  12. MILLER, G.H., P.H. DOUKAS, and J.K. SEYDEL: Sulfonamide structure-activity relationships in a cell-free system. Correlation of inhibition of folate synthesis with antibacterial activity and physicochemical parameters. J. Med. Chem. 15, 700–706 (1972).PubMedCrossRefGoogle Scholar
  13. ORTIZ, P.J. and R.D. HOTCHKISS: The enzymatic synthesis of dihydrofolate and dihydrophteroate in cell-free preparations from wildtype and sulfonamide-resistent pneumococcus. Biochemistry 5, 67–74 (1966).PubMedCrossRefGoogle Scholar
  14. SEYDEL, J.K.: Prediction of in vitroactivity of sulfonamides using Hammett constants or spectrophotometric data of the basic amines for calculation. Mol. Pharmacol. 2, 259–265 (1966).Google Scholar
  15. SEYDEL, J.K.: Molekulare Grundlagen der Sulfonamidwirkung. Arzneim.Forsch. 16, 1447–1453 (1966).Google Scholar
  16. SEYDEL, J.: Physicochemical approaches to the rational development of new drugs. Drug Design (Ariens, Edt.) Vol. 1, 343–379 (1971).Google Scholar
  17. SEYDEL, J.K.: Prediction of the in vitroactivity of sulfonamides synthesized from simple amines by use of electronic data obtained from the simple amines. J. Med. Chem. 14, 724–729 (1971).PubMedCrossRefGoogle Scholar
  18. SEYDEL, J.K., G.H. Miller, and P.H. DOUKAS: Structure-activity correlations of sulfonamides in cell-free systems compared to correlations obtained in whole cell systems and in vivo. (P. Pratesi, Edt.) Medicinal Chemistry, Butterworth, London 1973.Google Scholar
  19. SHEFTER, E., Z.F. CHMIELEWICZ, J.F. BLOUNT, T.F. BRENNAN, B.F. SACKMAN and P. SACKMAN: Biological implications of molecular and crystal structures of sulfadimethoxine, sulfadoxine, and sulfisoxazole. J. Pharm. Sci. 61, 872–877 (1972).PubMedCrossRefGoogle Scholar
  20. SHIOTA, T., M.N. DÏsraely, and M.P. McCANN: The enzymatic synthesis of folate like compounds from hydroxymethyldihydropteridine pyrophosphate. J. Biol. Chem. 239, 2259–2266 (1964).PubMedGoogle Scholar
  21. WEBB, J.L.: Enzyme and Metabolic Inhibitors. Vol. II, Academic Press, New York, London, 1966.Google Scholar
  22. WOODS, D.D.: The relation of p-aminobenzoic acid to the mechanism of the action of sulphanilamide. Brit. J. Exp. Path. 21, 74–90 (1940).Google Scholar

Copyright information

© Springer-Verlag/Wien 1975

Authors and Affiliations

  • Joachim K. Seydel

There are no affiliations available

Personalised recommendations