SB 205952, a novel semisynthetic monic acid analog with at least two modes of action.
The biological properties of SB 205952, a nitrofuryl oxazole derivative of monic acid, differ from those of the closely related antibacterial agent mupirocin. Compared with mupirocin, SB 205952 has increased antimicrobial potency, an extended spectrum including mupirocin-resistant staphylococci, and rapid bactericidal activity. SB 205952, like mupirocin, is a potent inhibitor of bacterial isoleucyl-tRNA synthetase (IRS) in mupirocin-susceptible organisms but does not inhibit IRS from mupirocin-resistant staphylococci, indicating that SB 205952 has more than one mechanism of action. SB 205952 rapidly inhibits protein, RNA, and DNA syntheses in mupirocin-susceptible and mupirocin-resistant staphylococci. In each case, the effect on RNA synthesis is relaxed by treatment with chloramphenicol, indicating that inhibition of RNA synthesis is probably a secondary consequence of stringent control. It is proposed that SB 205952 possesses one or more mechanisms of action in addition to IRS inhibition, probably mediated by its nitrofuryl component.
Wilson
J M
JM
SmithKline Beecham Pharmaceuticals, Brockham Park Research Centre, Betchworth, Surrey, United Kingdom.
Oliva
B
B
Cassels
R
R
O'Hanlon
P J
PJ
Chopra
I
I
D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects*; D001426:Bacterial Proteins / Q000096:biosynthesis; D004269:DNA, Bacterial / Q000096:biosynthesis; D004926:Escherichia coli / Q000187:drug effects; D008826:Microbial Sensitivity Tests; D016712:Mupirocin / Q000494:pharmacology; D010080:Oxazoles / Q000494:pharmacology*; D012329:RNA, Bacterial / Q000096:biosynthesis; D013211:Staphylococcus aureus / Q000187:drug effects
C097412:5-(5-nitrofur-2-yl)-2-(1-normon-2-yl)oxazole A; D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D004269:DNA, Bacterial; D010080:Oxazoles; D012329:RNA, Bacterial; D016712:Mupirocin