title: Isolation, structure and antibacterial activity of pleosporone from a pleosporalean ascomycete discovered by using antisense strategy.
abstract: Protein synthesis is one of the best antibacterial targets that have led to the development of a number of highly successful clinical drugs. Protein synthesis is catalyzed by ribosome, which is comprised of a number of ribosomal proteins that help the catalysis process. Ribosomal protein S4 (RPSD) 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. Screening of microbial extracts using antisense-sensitized rpsD Staphylococcus aureus strain led to the isolation of pleosporone, a new compound, with modest antibacterial activities with MIC ranging from 1 to 64 microg/mL. This compound showed the highest sensitivity for Streptococcus pneumoniae and Haemophilus influenzae, and exhibited MIC's of 4 and 1 microg/mL, respectively. Pleosporone showed modest selectivity for the inhibition of RNA synthesis compared to DNA and protein synthesis, and showed activity against HeLa cells. Isolation, structure elucidation, and biological activity of pleosporone have been described.
authors.affiliation: Merck Research Laboratories, Rahway, NJ 07065, USA.
authors.forename: Chaowei
authors.initials: C
authors.lastname: Zhang
authors.forename: John G
authors.initials: JG
authors.lastname: Ondeyka
authors.forename: Deborah L
authors.initials: DL
authors.lastname: Zink
authors.forename: Angela
authors.initials: A
authors.lastname: Basilio
authors.forename: Francisca
authors.initials: F
authors.lastname: Vicente
authors.forename: Javier
authors.initials: J
authors.lastname: Collado
authors.forename: Gonzalo
authors.initials: G
authors.lastname: Platas
authors.forename: Joann
authors.initials: J
authors.lastname: Huber
authors.forename: Karen
authors.initials: K
authors.lastname: Dorso
authors.forename: Mary
authors.initials: M
authors.lastname: Motyl
authors.forename: Kevin
authors.initials: K
authors.lastname: Byrne
authors.forename: Sheo B
authors.initials: SB
authors.lastname: Singh
mesh_terms: D000880:Anthraquinones / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D001203:Ascomycota / Q000737:chemistry*; D002851:Chromatography, High Pressure Liquid; D004354:Drug Screening Assays, Antitumor; D006193:Haemophilus influenzae / Q000187:drug effects; D006367:HeLa Cells; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D016376:Oligonucleotides, Antisense / Q000737:chemistry*; D021241:Spectrometry, Mass, Electrospray Ionization; D013211:Staphylococcus aureus / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects
chemical_list: D000880:Anthraquinones; D000900:Anti-Bacterial Agents; D016376:Oligonucleotides, Antisense; C541040:pleosporone