YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

${\beta}-Lactamase$ Inhibitory Activity and Comparative Activity of 6-Benzothiazole Penicillin Derivatives in Combination with ${\beta}-Lactam$ Antibiotics

6-벤조치아졸 페니실린 유도체의 베타락타마제 효소억제력과 베타락탐항생제 병용시 활성비교

  • Yoon, Sang-Bae (Division of Medicinal Chemistry, College of Pharmacy, Chung-ang University) ;
  • Im, Chae-Uk (Division of Medicinal Chemistry, College of Pharmacy, Chung-ang University)
  • 윤상배 (중앙대학교 약학대학 의약품화학 교실) ;
  • 임채욱 (중앙대학교 약학대학 의약품화학 교실)
  • Published : 2008.08.31
Download PDF
⟨ Previous Next ⟩

Abstract

In vitro ${\beta}-lactamase$ inhibitory activity of 6-benzothiazole penicillins (1, 2, 3 and 4) was compared with clavulanic acid, sulbactam and tazobactam. The inhibitory activity of exomethylene compounds (3 and 4) was stronger than those of non-exomethylene compounds (1 and 2). The sulfide 3 showed stronger inhibitory activity than sulbactam, clavulanic acid andsimilar to tazobactam against ${\beta}-lactamase$ Type I enzymes. The inhibitory activity of 4 was stronger than those of sulbactam, clavulanic acid and tazobactam against Type III and IV enzymes. The in vitro antimicrobial activity of ampicillin or cefoperazone combined with 3 or 4 was stronger than those of ampicillin or cefoperazone alone against many ${\beta}-lactamase$ producing strains to show that compounds 3 and 4 have some synergistic effect. The synergistic activity of 3 and 4 was comparable to sulbactam in some ${\beta}-lactamase$ producing strains, but it was inferior to tazobactam.

Keywords

References

  1. Sandanayaka, V. P. and Prashad, A. S. : Resistance to $\beta$-lactam antibiotics: Structure and mechanism based design of $\beta$- lactamase inhibitors. Current Med. Chem. 9, 1145 (2002) https://doi.org/10.2174/0929867023370031
  2. Jacoby, G. A. and Archer, G. L. : New mechanisms of bacterial resistance to antimicrobial agents. New Eng. J. Med. 324, 601 (1991) https://doi.org/10.1056/NEJM199102283240906
  3. Moland, E. S., Black, J. A., Ourada, J., Reisbig, M. D., Hanson, N. D. and Thomson, K. S. : Occurrence of newer $\beta$-lactamases in Klebsiella pneumoniae isolates from 24 U.S. Hospitals. Antimicrob. Agents Chemother. 46, 3837 (2002) https://doi.org/10.1128/AAC.46.12.3837-3842.2002
  4. Bennet, I., Broom, N. J. P., Bruton, G. S., Alvert, C., Clarke, B. P., Coleman, K., Edmondson, R., Edwards, P., Jones, D., Osbone, N. F. and Walker, G. : 6-(Substituted methylene)penems, potent broad spectrum inhibitors of bacterial $\beta$-lactamase. J. Antibiotics 44, 331 (1990)
  5. Mansour, T. S., Venkatesan, A. M., Bradford, P., Petersen, P. J. and Projan, S. J. : Tricyclic 6-alkylidene-penem $\beta$-lactamase inhibitors and $\beta$-lactam antibiotic combination for treatment of resistant infections. U.S. Pat 2007027130 A1 20070201 (2007)
  6. Venkatesan, A. M., Agarwal, A., Abe, T., Ushirogochi, H., Yamamura, I., Ado, M., Tsuyoshi, T., Dos, S. O., Gu, Y., Sum, F. W., Lin, Y. I., Petersen, P. J., Yang, Y., Kumagai, T., Weiss, W. J., Shlaes, D. M., Knox, J. R. and Mansour, T. S. : Structureactivity relationship of 6-methylidene penems bearing 6,5 bicyclic heterocycles as broad-spectrum $\beta$-lactamase inhibitors : Evidence for 1,4-thiazepine intermediates with C7 R stereochemistry by computational methods. J. Med. Chem. 49, 4623 (2006) https://doi.org/10.1021/jm060021p
  7. Plantan, I., Selic, L., Mesar, T., Stefanic, A. P., Oblak, M., Prezelj, A., Hesse, L., Andrejasic, M., Vilar, M., Turk, D., Kocijan, A., Prevec, T., Vilfan, G., Kocjan, D., Copar, A., Urleb, U. and Solmajer, T. : 4-Substituted trinems as broad spectrum $\beta$-lactamase inhibitors : Structure-based design, synthesis, and biological activity. J. Med. Chem. 50, 4113 (2007) https://doi.org/10.1021/jm0703237
  8. Aronoff, S. C., Jacobs, M. R., Johenning, S. and Yamabe. S. : Comparative activities of the $\beta$-lactamase inhibitors YTR830, sodium clavulanate, and sulbactam combined with amoxicillin or ampicillin. J. Antimicrob. Chemother. 26, 580 (1984) https://doi.org/10.1128/AAC.26.4.580
  9. Fassand, J. R. and Prior, B. R. : Comparative In vitro activities of piperacillin-tazobactam and ticarcillin-clavulanate. Antimicrob. Agents Chemother. 33, 1268 (1989) https://doi.org/10.1128/AAC.33.8.1268
  10. Maddux, S. M. : Effects of $\beta$-lactamases mediated antimicrobial resistance: The role of $\beta$-lactamases inhibitors. Pharmacother. 11, 40 (1991)
  11. Smith, J. T., Hamilton-Miller, J. M. T. and Knox, R. : Bacterial resistance to penicillins and cephalosporins. J. Pharm. Pharmac. 21, 337 (1969) https://doi.org/10.1111/j.2042-7158.1969.tb08267.x
  12. Waley, S. G. : A spectrophotometric assay of $\beta$-lactamase action on penicillins. Biochem. J. 139, 789 (1974) https://doi.org/10.1042/bj1390789
  13. Ross, G. W., Chanter, K. V., Harris, A. M., Kirby, S. M., Marshall, M. J. and O'Callaghan, C. H. : Comparison of assay techniques for $\beta$-lactamase activity. Anal. Biochem. 54, 9 (1973) https://doi.org/10.1016/0003-2697(73)90241-8
  14. American national standards institute : Methods for Dilution Antimicrobial Susceptibility Tests for Bacteria that grow Aerobically. 2nd. NCCLS Document M7-A2. 10, 1 (1990)