Isolation, structure, and antibacterial activity of phaeosphenone from a Phaeosphaeria sp. discovered by antisense strategy.
Zhang C, Ondeyka JG, Zink DL, Basilio A, Vicente F, Collado J, Platas G, Bills G, Huber J, Dorso K, Motyl M, Byrne K, Singh SB.
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.