Discovery of 1,4-dihydroxy-2-naphthoate [corrected] prenyltransferase inhibitors: new drug leads for multidrug-resistant gram-positive pathogens

J Med Chem. 2007 Aug 23;50(17):3973-5. doi: 10.1021/jm070638m. Epub 2007 Jul 21.

Abstract

Since utilization of menaquinone in the electron transport system is a characteristic of Gram-positive organisms, the 1,4-dihydroxy-2-naphthoate prenyltransferase (MenA) inhibitors 1a and 2a act as selective antibacterial agents against organisms such as methicillin-resistant Stapylococcus aureus (MRSA), Staphylococcus epidermidis (MRSE), and Mycobacterium spp. Growth of drug-resistant Gram-positive organisms was sensitive to the MenA inhibitors, indicating that menaquinone synthesis is a valid new drug target in Gram-positive organisms.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Alkyl and Aryl Transferases / metabolism
  • Anti-Bacterial Agents / chemical synthesis*
  • Anti-Bacterial Agents / chemistry
  • Anti-Bacterial Agents / pharmacology
  • Benzophenones / chemical synthesis*
  • Benzophenones / chemistry
  • Benzophenones / pharmacology
  • Gram-Positive Bacteria / drug effects*
  • Gram-Positive Bacteria / enzymology
  • Methicillin Resistance
  • Microbial Sensitivity Tests
  • Mycobacterium / drug effects
  • Mycobacterium / enzymology
  • Naphthols / metabolism*
  • Staphylococcus aureus / drug effects
  • Staphylococcus aureus / enzymology
  • Staphylococcus epidermidis / drug effects
  • Staphylococcus epidermidis / enzymology

Substances

  • Anti-Bacterial Agents
  • Benzophenones
  • Naphthols
  • allylaminomethanone-A
  • phenethylaminomethanone-A
  • 1,4-dihydroxy-2-naphthoic acid
  • Alkyl and Aryl Transferases