title: Coniothyrione, a chlorocyclopentandienylbenzopyrone as a bacterial protein synthesis inhibitor discovered by antisense technology.
abstract: Bacterial protein synthesis inhibitors interact mainly with rRNA and to some extent ribosomal proteins, which are potential targets for developing new antibacterial agents. Specifically, the ribosomal protein S4 of the 30s ribosomal subunit known as ribosomal protein small-subunit D (rpsD) may be useful as a target. The antisense-rpsD gene-sensitized two-plate assay led to the discovery of a novel chlorinated cyclopentandienylbenzopyrone antibiotic, coniothyrione, C14H9ClO6, isolated from Coniothyrium cerealis MF7209. It exhibited liquid MICs of 16-32 microg/mL against Staphylococcus aureus, Bacillus subtilis, Haemophilus influenzae, Streptococcus pneumoniae, and Enterococcus faecalis and >64 microg/mL against Escherichia coli. Isolation, structure elucidation, and antibacterial activity of coniothyrione are described.
authors.affiliation: Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA. john_ondeyka@merck.com
authors.forename: John G
authors.initials: JG
authors.lastname: Ondeyka
authors.forename: Deborah
authors.initials: D
authors.lastname: Zink
authors.forename: Angela
authors.initials: A
authors.lastname: Basilio
authors.forename: Francisca
authors.initials: F
authors.lastname: Vicente
authors.forename: Gerald
authors.initials: G
authors.lastname: Bills
authors.forename: Maria Teresa
authors.initials: MT
authors.lastname: Diez
authors.forename: Mary
authors.initials: M
authors.lastname: Motyl
authors.forename: Gabe
authors.initials: G
authors.lastname: Dezeny
authors.forename: Kevin
authors.initials: K
authors.lastname: Byrne
authors.forename: Sheo B
authors.initials: SB
authors.lastname: Singh
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D001412:Bacillus subtilis / Q000187:drug effects; D001419:Bacteria / Q000187:drug effects*; D002867:Chromones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D016373:DNA, Antisense / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D011500:Protein Synthesis Inhibitors / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D016372:RNA, Antisense / Q000737:chemistry; D012269:Ribosomal Proteins; D013030:Spain; D013211:Staphylococcus aureus / Q000187:drug effects; D013296:Streptococcus pneumoniae / Q000187:drug effects
chemical_list: D000900:Anti-Bacterial Agents; D002867:Chromones; D016373:DNA, Antisense; D011500:Protein Synthesis Inhibitors; D016372:RNA, Antisense; D012269:Ribosomal Proteins; C519757:coniothyrione; C031798:ribosomal protein S4