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Antimicrobial Agents and Chemotherapy, August 2009, p. 3331-3336, Vol. 53, No. 8
0066-4804/09/$08.00+0     doi:10.1128/AAC.00226-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Pyrazolopyrimidinediones Are Selective Agents for Helicobacter pylori That Suppress Growth through Inhibition of Glutamate Racemase (MurI){triangledown}

B. L. M. de Jonge,* A. Kutschke, M. Uria-Nickelsen, H. D. Kamp,{dagger} and S. D. Mills

Infection Discovery, Cancer and Infection Research Area, 35 Gatehouse Drive, Waltham, Massachusetts

Received 18 February 2009/ Returned for modification 21 March 2009/ Accepted 5 May 2009

Pyrazolopyrimidinediones are a novel series of compounds that inhibit growth of Helicobacter pylori specifically. Using a variety of methods, advanced analogues were shown to suppress the growth of H. pylori through the inhibition of glutamate racemase, an essential enzyme in peptidoglycan biosynthesis. The high degree of selectivity of the series for H. pylori makes these compounds attractive candidates for novel H. pylori-selective therapy.

* Corresponding author. Mailing address: Infection Discovery, Cancer and Infection Research Area, 35 Gatehouse Drive, Waltham, MA 02451. Phone: (781) 839-4535. Fax: (781) 839-4500. E-mail: Boudewijn.deJonge{at}astrazeneca.com

{triangledown} Published ahead of print on 11 May 2009.

{dagger} Present address: Department of Microbiology and Molecular Genetics, Harvard Medical School, Boston, MA 02115-6092.

Antimicrobial Agents and Chemotherapy, August 2009, p. 3331-3336, Vol. 53, No. 8
0066-4804/09/$08.00+0     doi:10.1128/AAC.00226-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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