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

• Published in: Bioorganic & medicinal chemistry letters 1999-10, Vol.9 (20), p.2947-2952
• Main Authors: Kanojia, Ramesh M., Murray, William, Bernstein, Jeffrey, Fernandez, Jeffrey, Foleno, Barbara D., Krause, Heather, Lawrence, Laura, Webb, Glenda, Barrett, John F.
• Format: Article
• Language: English
• Subjects: Anacardic Acids; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacteria - enzymology; Biological and medical sciences; Enzyme Inhibitors - pharmacology; Histidine Kinase; Medical sciences; Microbial Sensitivity Tests; Pharmacology. Drug treatments; Protein Kinase Inhibitors; Protein Kinases - metabolism; Salicylates - chemistry; Salicylates - pharmacology; Structure-Activity Relationship
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/S0960-894X(99)00508-9

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 (IC 50 values ≤ 5 μM) 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. A series of 6-oxa isosteres 1 of anacardic acids (6-higher alkyl/alkenyl-2-hydroxybenzoic acids) was synthesised and several members were discovered to be among the most potent inhibitors (IC 50 values ≤ 5 μM) 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. [Display omitted]