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The inhibition of metallo-β-lactamase by thioxo-cephalosporin derivatives

Tsang, Wing Y., Dhanda, Anupma, Schofield, Christopher J., Frere, Jean-Marie, Galleni, Moreno and Page, Michael I. (2004) The inhibition of metallo-β-lactamase by thioxo-cephalosporin derivatives. Bioorganic & Medicinal Chemistry Letters, 14 (7). pp. 1737-1739. ISSN 0960-894X

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The 8-thioxocephalosporins are poor substrates for the B. cereus metallo β-lactamase (kcat/Km=61.4 M−1 s−1) and act as weak competitive inhibitors (Ki 700 μM). The hydrolysis product of thioxocephalosporin, a thioacid, also inhibits the enzyme competitively with a Ki=96 μM, whereas the cyclic thioxo-piperazinedione, formed by intramolecular aminolysis of thioxocephalexin has a Ki of 29 μM.

Item Type: Article
Subjects: Q Science > Q Science (General)
Q Science > QD Chemistry
Schools: School of Applied Sciences
School of Applied Sciences > Biomolecular Sciences Research Centre
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1. Wiberg, K. B.; Rush, D. J. J. Am. Chem. Soc. 2001, 123,
2038. Wiberg, K. B.; Rush, D. J. J. Org. Chem. 2002, 67,
826. Lauvergnat, D.; Hiberty, P. C. J. Am. Chem. Soc.
1997, 119, 9478.
2. Min, B. K.; Lee, H.-J.; Choi, Y. S.; Park, J.; Yoon, C-J.;
Yu, J.-A. J. Mol. Struct. 1998, 471, 283.
3. Tsang, W. Y.; Dhanda, A.; Schofield, C. J.; Page, M. I. J.
Org. Chem. 2004, 69, 339. Jiang, Z. X. D. Phil thesis,
University of Oxford, 1997.
4. Wiberg, K. B.; Rablem, P. R. J. Am. Chem. Soc. 1995,
117, 2201.
5. Bordwell, F. G.; Ji, G.-Z. J. Am. Chem. Soc. 1991, 113,
6. Page, M. I.; Laws, A. P. Chem. Commun. 1998, 1609.
7. Murphy, B. P.; Pratt, R. F. Biochem. J. 1989, 258, 765.
8. Bounaga, S.; Laws, A. P.; Galleni, M.; Page, M. I.
Biochem. J. 1998, 331, 703. Bounaga, S.; Laws, A. P.;
Galleni, M.; Page, M. I. Bioorg. Med. Chem. 2001, 9,
9. Concha, N. O.; Janson, C. A.; Rowling, P.; Pearson, S.;
Cheever, C. A.; Clarke, B. P.; Lewis, C.; Galleni, M.;
Frere, J.-M.; Payne, D. J.; Bateson, J. H.; Abdel-Meguid,
S. S. Biochemistry 2000, 39, 4288.
10. Payne, D. J.; Bateson, J. H.; Gasson, B. C.; Khushi, T.;
Proctor, D.; Pearson, S. C.; Reid, R. FEMS Microbiol.
Lett. 1997, 157, 171.
11. Gilpin, M. L.; Fulston, M.; Payne, D.; Cramp, R.; Hood,
I. J. Antibiot. 1995, 48, 1081. Walter, M. W.; Felici, A.;
Galleni, M.; Soto, R. P.; Adlington, R. M.; Baldwin, J. E.;
Fre` re, J.-M.; Gololobov, M.; Schofield, C. J. Bioorg. Med.
Chem. Lett. 1996, 6, 2455. Goto, M.; Takahashi, T.;
Yamashita, F.; Koreeda, A.; Mori, H.; Ohta, M.; Arakawa,
Y. Biol. Pharm. Bull. 1997, 20, 1136. Toney, J. H.;
Fitzgerald, P. M. D.; Grover-Sharma, N.; Olson, S. H.;
May, W. J.; Sundelof, J. G.; Vanderwall, D. E.; Cleary,
K. A.; Grant, S. K.; Wu, J. K.; Kozarich, J. W.; Pompliano,
D. L.; Hammond, G. G. Chem. Biol. 1998, 5, 185.
Greenlee, M. L.; Laub, J. B.; Balkovec, J. M.; Hammond,
M. L.; Hammond, G. G.; Pompliano, D. L.; Epstein-
Toney, J. H. Bioorg. Med. Chem. Lett. 1999, 2549. Toney,
J. H.; Cleary, K. A.; Hammond, G. G.; Yuan, X.; May,
W. J.; Hutchins, S. M.; Ashton, W. T.; Vanderwall, D. E.
Biorg. Med. Chem. Lett. 1999, 9, 2741. Walter, M. W.;
Valladares, M. H.; Adlington, R. M.; Amicosante, G.;
Baldwin, J. E.; Fre´ re, J.-M.; Galleni, M.; Rossolini, G. M.;
Schofield, C. J. Bioorg. Chem. 1999, 27, 35. Nagano, R.;
Adachi, Y.; Imamura, H.; Yamada, K.; Hashizume, T.;
Morishima, H. Antimicrob. Agents and Chemother. 1999,
43, 2497. Yang, K. W.; Crowder, M. W. Arch. Biochem.
Biophys. 1999, 368, 1.
12. Payne, D. J.; Bateson, J. H.; Gasson, B. C.; Proctor, D.;
Khushi, T.; Farmer, T. H.; Tolson, D. A.; Bell, D.; Skett,
P. W.; Marshall, A. C.; Reid, R.; Ghosez, L.; Combret,
Y.; Marchand-Brynaert, J. Antimicrob. Agents and Chemother.
1997, 41, 135.
13. Hammond, G. G.; Huber, J. L.; Greenlee, M. L.; Laub,
J. B.; Young, K.; Silver, L. L.; Balkovec, J. M.; Pryor,
K. D.; Wu, J. K.; Leiting, B.; Pompliano, D. L.; Toney,
J. H. FEMS Microbiol. Lett. 1999, 179, 289.
14. Bundgaard, H. Arch. Pharm. Chem. Sci. Ed. 1976, 4, 25.
15. Hancock, R. D.; Martell, A. E. Adv. Inorg. Chem. 1995,
42, 89.
16. Szardenings, A. K.; Burkoth, T. S.; Lu, H. H.; Tien,
D. W.; Campbell, D. A. Tetrahedron 1997, 53, 6573.
Goodfellow, V. S.; Laudeman, C. P.; Gerrity, J. I.; Burkard,
M.; Strobel, E.; Zuzack, J. S.; McLeod, D. A. Mol.
Divers. 1996, 2, 97.

Depositing User: Sara Taylor
Date Deposited: 08 Feb 2008 15:24
Last Modified: 24 Nov 2008 15:31


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