New antifungal antibiotics, benanomicins A and B from an Actinomycete.

Synthesis and antifungal activity of pradimicin derivatives. Modifications on the aglycone part.

“…It has been noted that compounds (3, 6 and 7 and 7-hydroxy PRMA7)), having different conformation from that of PRMA showed no antifungal activity. Although the 1-OMe derivative (2) showed apparently decreased activity, 1 1-0-demethyl (ll) and 1 1-demethoxy (12) derivatives showed The same compoundll was recently isolated by fermentation in our laboratory and designated pradimicin H. SEPT. 1993 significant activity comparable to that of PRMA.…”

Mode of Antifungal Action of Benanomicin A in Saccharomyces cerevisiae.

“…The results obtained are summarized as follows: (1) benanomicin A at relatively high concentrations (almost equal to MIC) was fungicidal and disrupted the cell permeability barrier, inducing leakage of intracellular K+and ATPin growing cells, while the antibiotic had none of these effects in non-growing cells; (2) no biosynthesis of any of several major cellular constituents in yeast cells was inhibited markedly or selectively enough to explain its fungitoxic activity; (3) whereas benanomicin A induced lysis ofmetabolically active yeast protoplasts incubated in the presence of glucose, inactive yeast protoplasts incubated without glucose were refractory to the lytic action of the antibiotic; (4) osmotically shocked yeast cells became feasible to the cidal action ofbenanomicin A; (5) benanomicin A substantially inhibited uptake of 6-deoxy-glucose by yeast cells; (6) liposomes composed of phospholipids and cholesterol were not susceptible to benanomicin A; and (7) benanomicin A inhibited in vitro activity of H+-ATPase from yeast cell membranes to a greater extent than that for H+-ATPasefrom yeast mitochondria or H+-ATPasefrom yeast vacuolar membranes.…”

Successful treatment of Pneumocystis carinii Pneumonia in mice with benanomicin A (ME1451)

“…BNM-A is produced by Actinomadura sp. strain MH193-16F4, isolated as a red powder, and readily soluble in water as its sodium salt (17). It belongs to a new family of benzonaphthacene antifungal antibiotics (Fig.…”