Coniothyrione, a chlorocyclopentandienylbenzopyrone as a bacterial protein synthesis inhibitor discovered by antisense technology.
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.
Ondeyka
John G
JG
Merck Research Laboratories, P.O. Box 2000, Rahway, New Jersey 07065, USA. john_ondeyka@merck.com
Zink
Deborah
D
Basilio
Angela
A
Vicente
Francisca
F
Bills
Gerald
G
Diez
Maria Teresa
MT
Motyl
Mary
M
Dezeny
Gabe
G
Byrne
Kevin
K
Singh
Sheo B
SB
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
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