Mutactimycin E, a new anthracycline antibiotic with gram-positive activity.
Resistance to currently available antibiotics has become a widely recognized crisis in the medical community. To address this, many companies and researchers are refocusing their attention towards natural products, which have an excellent track record of producing effective antibacterial drugs. The AMRI natural product library was screened for activity against multi-drug resistant Staphylococcus aureus (MDRSA). The active samples were counter screened for cytotoxicity against the human hepatocellular carcinoma HepG2 cell line to determine an in vitro therapeutic index (in vitro TI). Those samples with a high in vitro TI were selected for fractionation and dereplication. This led to the discovery of a new anthracycline structure. This metabolite, named mutactimycin E (1), exhibited moderate activity against several gram positive organisms. Here we report the isolation, structure elucidation and biological activities of this new compound.
Hopp
D Craig
DC
AMRI, Bothell Research Center, Bothell, WA 98011, USA.
Rabenstein
John
J
Rhea
Joshua
J
Smith
Chris
C
Romari
Khadidja
K
Clarke
Midori
M
Francis
Linda
L
Irigoyen
Macarena
M
Milanowski
Dennis
D
Luche
Michele
M
Carr
Grant J
GJ
Mocek
Ulla
U
D018943:Anthracyclines / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D006094:Gram-Positive Bacteria / Q000187:drug effects*; D022781:Hepatocytes / Q000187:drug effects; D006801:Humans; D015394:Molecular Structure; D054852:Small Molecule Libraries; D013057:Spectrum Analysis
D018943:Anthracyclines; D000900:Anti-Bacterial Agents; D054852:Small Molecule Libraries; C540753:mutactimycin E