"Synthesis and Biological Evaluation of thiazolidine-2-one 1,1-dioxide as Inhibitors of Escherichia coli β-ketoacyl-ACP-synthase III (FabH)" by Mamoun M. Alhamadsheh

Article

Synthesis and Biological Evaluation of thiazolidine-2-one 1,1-dioxide as Inhibitors of Escherichia coli β-ketoacyl-ACP-synthase III (FabH)

Bioorganic & Medicinal Chemistry Letters (2006)

Mamoun M. Alhamadsheh, Portland State University
Norman C. Waters, Walter Reed Army Institute of Research
Donald P. Huddler, Walter Reed Army Institute of Research
Mara Kreishman-Deitrick Kreishman-Deitrick, Walter Reed Army Institute of Research
Galina Florova, Portland State University
Kevin A. Reynolds, Portland State University

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Abstract

A series of cyclic sulfones has been synthesized and their activity against β-ketoacyl-ACP-synthase III (FabH) has been investigated. The compounds are selectively active against Escherichia coli FabH (ecFabH), but not Mycobacterium tuberculosis FabH (mtFabH) or Plasmodium falciparum KASIII (PfKASIII). The activity against ecFabH ranges from 0.9 to >100 μM and follows a consistent general SAR trend. Many of the compounds were shown to have antimalarial activity against chloroquine (CQ)-sensitive (D6) P. falciparum (IC50 = 5.3 μM for the most potent inhibitor) and some were active against E. coli (MIC = 6.6 μg/ml for the most potent inhibitor).

Disciplines

Chemistry

Publication Date

December 1, 2006

DOI

10.1016/j.bmcl.2006.11.067

Citation Information

Alhamadsheh, M.M., Waters, N.C., Huddler, D.P., Kresihamn-Deitrick, D., Florova, G., and Reynolds, K. A. Synthesis and biological evaluation of thiazolidine-2-one 1,1-dioxide as inhibitors of Escherichia coli beta-ketoacyl-ACP-synthase III (FabH). Bioorganic Med. Chem. Lett., Dec 1: 17, 879-83, 2007