Isolation, structure, and antibacterial activity of phaeosphenone from a Phaeosphaeria sp. discovered by antisense strategy.
Ribosomal protein S4 (RPSD), a part of the ribosomal small subunit, is one of the proteins that is a part of the ribosomal machinery and is a potential new target for the discovery of antibacterial agents. Continued screening of microbial extracts using antisense-sensitized rpsD Staphylococcus aureus strain led to the isolation of a new dimeric compound, phaeosphenone (2). Compound 2 showed broad-spectrum antibacterial activity against Gram-positive bacteria, exhibiting MIC values ranging from 8 to 64 microg/mL. Phaeosphenone showed the highest sensitivity for Streptococcus pneumoniae (8 microg/mL) and inhibited the growth of Candida albicans with an MIC of 8 microg/mL. Phaeosphenone showed a modest selectivity for the inhibition of RNA synthesis over DNA and protein synthesis in S. aureus.
Merck Research Laboratories, Rahway, New Jersey 07065, USA.
Chaowei
C
Zhang
John G
JG
Ondeyka
Deborah L
DL
Zink
Angela
A
Basilio
Francisca
F
Vicente
Javier
J
Collado
Gonzalo
G
Platas
Gerald
G
Bills
Joann
J
Huber
Karen
K
Dorso
Mary
M
Motyl
Kevin
K
Byrne
Sheo B
SB
Singh
D000880:Anthraquinones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D016375:Antisense Elements (Genetics); D001203:Ascomycota / Q000737:chemistry*; D002176:Candida albicans / Q000187:drug effects; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D008969:Molecular Sequence Data; D015394:Molecular Structure; D019384:Nucleic Acid Synthesis Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D012269:Ribosomal Proteins / Q000187:drug effects*; D013211:Staphylococcus aureus / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects
D000880:Anthraquinones; D000900:Anti-Bacterial Agents; D016375:Antisense Elements (Genetics); D019384:Nucleic Acid Synthesis Inhibitors; D012269:Ribosomal Proteins; C531889:phaeosphenone; C031798:ribosomal protein S4