Chemical modifications of the antibiotic purpuromycin.
Purpuromycin, isolated in our laboratories from the culture broth of Actinoplanes ianthinogenes, is very active in vitro against Gram-positive bacteria and fungi and shows variable activity against Gram-negative bacteria. Its poor bioavailability, probably due to its insolubility in aqueous media at physiological pH's, and the fact that its activity is antagonized by serum, led us to plan a chemical program with the aim of understanding the relevance of the substituents for the antibiotic activity. The original 7-methoxycarbonyl group was transformed into more hydrophilic groups by hydrolysis, by reduction and by ammonolysis or in esters with different degree of lipophilicity and steric hindrance. Almost all of the derivatives retained activity against Gram-positive bacteria but lost activity against Escherichia coli and Trichophyton mentagrophytes. Like purpuromycin, all of the derivatives show a reduced activity in the presence of serum.
Trani
A
A
MMDRI Centro Ricerche Lepetit, Varese, Italy.
Kettenring
J
J
Ripamonti
F
F
Goldstein
B
B
Ciabatti
R
R
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000737:chemistry; D008826:Microbial Sensitivity Tests; D009285:Naphthoquinones / Q000737:chemistry; D013329:Structure-Activity Relationship
D000900:Anti-Bacterial Agents; D009285:Naphthoquinones; C009115:purpuromycin