Discovery of 1,4-dihydroxy-2-naphthoate [corrected] prenyltransferase inhibitors: new drug leads for multidrug-resistant gram-positive pathogens.
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.
Kurosu
Michio
M
Department of Microbiology, Immunology, and Pathology, College of Veterinary Medicine and Biomedical Sciences, Colorado State University, 1682 Campus Delivery, Fort Collins, Colorado 80523-1682, USA. michio.kurosu@colostate.edu
Narayanasamy
Prabagaran
P
Biswas
Kallolmay
K
Dhiman
Rakesh
R
Crick
Dean C
DC
D019883:Alkyl and Aryl Transferases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001577:Benzophenones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006094:Gram-Positive Bacteria / Q000187:drug effects* / Q000201:enzymology; D016106:Methicillin Resistance; D008826:Microbial Sensitivity Tests; D009161:Mycobacterium / Q000187:drug effects / Q000201:enzymology; D009284:Naphthols / Q000378:metabolism*; D013211:Staphylococcus aureus / Q000187:drug effects / Q000201:enzymology; D013212:Staphylococcus epidermidis / Q000187:drug effects / Q000201:enzymology
D000900:Anti-Bacterial Agents; D001577:Benzophenones; D009284:Naphthols; C523810:allylaminomethanone-A; C523811:phenethylaminomethanone-A; C024023:1,4-dihydroxy-2-naphthoic acid; D019883:Alkyl and Aryl Transferases