6-oxa isosteres of anacardic acids as potent inhibitors of bacterial histidine protein kinase (HPK)-mediated two-component regulatory systems

R M Kanojia; W Murray; J Bernstein; J Fernandez; B D Foleno; H Krause; L Lawrence; G Webb; J F Barrett

doi:10.1016/s0960-894x(99)00508-9

6-oxa isosteres of anacardic acids as potent inhibitors of bacterial histidine protein kinase (HPK)-mediated two-component regulatory systems

Bioorg Med Chem Lett. 1999 Oct 18;9(20):2947-52. doi: 10.1016/s0960-894x(99)00508-9.

Authors

R M Kanojia¹, W Murray, J Bernstein, J Fernandez, B D Foleno, H Krause, L Lawrence, G Webb, J F Barrett

Affiliation

¹ The R. W. Johnson Pharmaceutical Research Institute, Raritan, NJ 08869-0602, USA.

PMID: 10571153
DOI: 10.1016/s0960-894x(99)00508-9

Abstract

A series of 6-oxa isosteres of anacardic acids (6-higher alkyl/alkenyl-2-hydroxybenzoic acids) was synthesised and several members were discovered to be among the most potent inhibitors (IC50 values < or = 5 microM) of the bacterial two-component regulatory systems, KinA/SpoOF and NRII/NRI, reported to date. The Gram-positive antibacterial activity in selected strains is also presented.

MeSH terms

Anacardic Acids*
Anti-Bacterial Agents / chemistry
Anti-Bacterial Agents / pharmacology
Bacteria / enzymology*
Enzyme Inhibitors / pharmacology*
Histidine Kinase
Microbial Sensitivity Tests
Protein Kinase Inhibitors*
Protein Kinases / metabolism
Salicylates / chemistry
Salicylates / pharmacology*
Structure-Activity Relationship

Substances

Anacardic Acids
Anti-Bacterial Agents
Enzyme Inhibitors
Protein Kinase Inhibitors
Salicylates
anacardic acid
Protein Kinases
Histidine Kinase