Bulletin of the Korean Chemical Society

Korean Chemical Society (대한화학회)
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Structure-Activity Relationship Study on Cephalosporins with Mechanism-based Descriptors

  • Jun-Ho Choi (Department of Chemistry, Seoul National University) ;
  • Hojing Kim (Department of Chemistry, Seoul National University)
  • Published : 1993.10.20
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Abstract

The polarizability and the transition state energy of a cephalosporin are assumed to be theoretical indices of the permeability through the outer membrane and of reactivity of ${\beta}$ -lactam ring with penicillin binding proteins, respectively, in Gram-negative bacteria. They are computed by AM1 method and used as variables of quantitative structure-activity relationship study. The results justify quadratic dependence of the activity on the variables. The intersection of difference volumes between $\beta-lactamase$ stable cephalosporins and unstable ones manifests that the steric hindrance of 7-side chain is responsible for the ${\beta}$ -lactamase stability.

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References

  1. Proc. Natl. Acad. Sci. U.S.A. v.76 R. R. Yocum;D. J. Wasman;J. R. Rasmussen;J. L. Strominger
  2. Annu. Rev. Microbiol. v.33 A. Tomasz
  3. Clin. Pharmacokinet. v.11 R. Wise
  4. Antibicrob. Agents Chemother. v.34 J. Trais;H. Nikaido
  5. Chem. Rev. v.89 M. J. Miller
  6. Pharmacol. Ther. v.27 H. Nikaido
  7. Philos, Trans. R. Soc. London, Ser. B v.289 R. P. Ambler
  8. Br. Med. Bull. v.40 A. A. Medeiros
  9. Theoretical drug design methods R. Franke
  10. Special Publication No. 28 Recent Advances in the Chemistry of $\beta$-lactam Antibiotics J. Elks(ed.)
  11. Drug Intell. Clin. Pharm. v.19 T. A. Tartaglione;R. E. Dolk
  12. J. Med. Chem. v.33 S. Y. Sit;R. A. Parker;I. Motoc;W. Han;N. Balasubramanian;J. D. Catt;P. J. Brown;W. E. Harte;M. D. Thompson;J. J. Wright
  13. J. Am. Chem. Soc. v.102 D. B. Boyd;D. K. Herron;W. H. Lunn;W. A. Spitzer
  14. Ann. N. Y. Acad. Sci. v.367 D. B. Boyd
  15. J. Med. Chem. v.26 D. B. Boyd
  16. Frontiers of Antibiotic Research H. Umezawa(ed.)
  17. Antibiotics, an intergrated view G. C. Lancini(ed.)
  18. J. Am. Chem. Soc. v.86 C. Hansch;T. Fujita
  19. J. Am. Chem. Soc. v.92 R. M. Sweet;L. F. Dahls
  20. program Desktop Molecular Modeller(Version 1.2.) M. James;C. Crabbe
  21. GEOMOS program QCPE No. 584 D. Rinaldi;P. E. Hoggan;A. Cartier
  22. $SPSS^X$ User's Guide SPSS Inc.
  23. InsightII(Ver. 2.1.2.) Biosym Technologies Inc.
  24. Comprehensive Medicinal Chemistry v.2 P. G. Sammes(ed.)