Archazolids, new cytotoxic macrolactones from Archangium gephyra (Myxobacteria). Production, isolation, physico-chemical and biological properties.
Novel cytotoxic compounds, archazolid A and B, were isolated from the culture broth of strains of the myxobacteria Archangium gephyra and Cystobacter sp. Archazolids consist of a macrocyclic lactone ring with a thiazole side chain and showed high activity against mammalian cells. The IC50 values with different cell lines ranged from 0.1 to 1 ng/ml. An incubation of PtK2 potoroo cells with archazolid A (5 ng/ml) led to the formation of vacuoles in the ER, a phenomenon that is typical for inhibitors of V-ATPases, like concanamycin and bafilomycin. We therefore assume that archazolid is an inhibitor of the V-ATPase of higher cells.
Sasse
Florenz
F
GBF, German Research Centre for Biotechnology, Department Natural Product Biology, Mascheroder Weg 1, D-38124 Braunschweig, Germany. fsa@gbf.de
Steinmetz
Heinrich
H
Höfle
Gerhard
G
Reichenbach
Hans
H
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use; D005260:Female; D005285:Fermentation; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D007783:Lactones / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use; D008297:Male; D051379:Mice; D008826:Microbial Sensitivity Tests; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000903:Antibiotics, Antineoplastic; D007783:Lactones