Synthesis of a novel inhibitor against MRSA and VRE: Preparation from zerumbone ring opening material showing histidine-kinase inhibition

• Published in: Bioorganic & medicinal chemistry letters Vol. 17; no. 4; pp. 1098 - 1101
• Main Authors: Kitayama, Takashi, Iwabuchi, Risa, Minagawa, Shu, Sawada, Seiji, Okumura, Ryo, Hoshino, Kazuki, Cappiello, John, Utsumi, Ryutaro
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15.02.2007; Elsevier
• Subjects: Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Bacillus subtilis; Bacillus subtilis - enzymology; Biological and medical sciences; Drug-resistant bacterium; Enterococcus faecalis - drug effects; Histidine Kinase; Inhibitor; Medical sciences; Methicillin Resistance - drug effects; Microbial Sensitivity Tests; MRSA; Pharmacology. Drug treatments; Phosphorylation; Protein Kinases - drug effects; Sesquiterpenes - chemical synthesis; Sesquiterpenes - pharmacology; Staphylococcus aureus - drug effects; Staphylococcus aureus - enzymology; Tryptophan - analogs & derivatives; Tryptophan - pharmacology; Two-component system; VRE; YycG; Zerumbone; Zerumbone; Two-component system; MRSA; VRE; Inhibitor; YycG; Drug-resistant bacterium; Histidine kinase; Enterococcus faecalis; Vancomycin; Ring cleavage; Meticillin; Signal transduction; Structure activity relation; Sesquiterpenes; Bacteria; Micrococcales; Bromine Organic compounds; Micrococcaceae; Chemical synthesis; Staphylococcus aureus; Terpenoid; Enzyme; Aliphatic compound; Transferases; Enzyme inhibitor; In vitro; Resistance; Streptococcaceae; α-Aminoacid; Protein kinase; Antibacterial agent
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2006.11.015

The synthesis of the novel YycG inhibitor 34 (IC 50 = 43.9 μM) showing growth inhibition against MRSA and VRE is reported. Zerumbone ring-opening derivative 2 inhibited autophosphorylation of the essential histidine protein kinase (HPK), YycG, existing in Bacillus subtilis constituting a two-component system (TCS). However, it did not inhibit drug-resistant bacterium such as MRSA and VRE. Tryptophan derivative 34 also could be regulated by a TCS system like 2. In addition, 34 showed good inhibition against MRSA and VRE.