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.
SmithKline Beecham Pharmaceuticals, Brockham Park Research Centre, Betchworth, Surrey, United Kingdom.
J M
JM
Wilson
B
B
Oliva
R
R
Cassels
P J
PJ
O'Hanlon
I
I
Chopra
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