Abstract
A series of cyclic sulfones has been synthesized and their activity against beta-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 >100microM and follows a consistent general SAR trend. Many of the compounds were shown to have antimalarial activity against chloroquine (CQ)-sensitive (D6) P. falciparum (IC(50)=5.3microM for the most potent inhibitor) and some were active against E. coli (MIC=6.6microg/ml for the most potent inhibitor).
Publication types
-
Research Support, N.I.H., Extramural
MeSH terms
-
3-Oxoacyl-(Acyl-Carrier-Protein) Synthase / antagonists & inhibitors*
-
Amino Acid Sequence
-
Animals
-
Anti-Bacterial Agents / chemical synthesis*
-
Anti-Bacterial Agents / pharmacology*
-
Enzyme Inhibitors / chemical synthesis*
-
Enzyme Inhibitors / pharmacology*
-
Escherichia coli / drug effects*
-
Escherichia coli / enzymology*
-
Indicators and Reagents
-
Microbial Sensitivity Tests
-
Models, Molecular
-
Molecular Sequence Data
-
Mycobacterium tuberculosis / drug effects
-
Oxides / chemical synthesis*
-
Oxides / pharmacology*
-
Plasmodium falciparum / drug effects
-
Structure-Activity Relationship
-
Thiazolidines / chemical synthesis*
-
Thiazolidines / pharmacology*
Substances
-
Anti-Bacterial Agents
-
Enzyme Inhibitors
-
Indicators and Reagents
-
Oxides
-
Thiazolidines
-
thiazolidine-2-one 1,1-dioxide
-
3-Oxoacyl-(Acyl-Carrier-Protein) Synthase