Galbonolides A and B - two new non-glycosidic antifungal macrolides from

Achenbach, Hans; Mühlenfeld, Andreas; Fauth, U.; Zähner, Hans

doi:10.1016/s0040-4039(00)95043-3

Cited by 28 publications

(17 citation statements)

References 1 publication

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“…It was isolated from fermentations of Micromonospora chalcea and named rustmicin for its activity against wheat stem rust fungus (Puccinia graminis) (19). Almost simultaneously, the same structural compound was reported as galbonolide A from Streptomyces galbus culture broths, with potent activity against Botrytis cinerea and several other phytopathogens (20,21). Mode of action studies indicated that rustmicin did not destabilize the membrane or inhibit the synthesis of chitin, DNA, or RNA, but the mechanism of fungal growth inhibition was not determined (22).…”

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confidence: 99%

Rustmicin, a Potent Antifungal Agent, Inhibits Sphingolipid Synthesis at Inositol Phosphoceramide Synthase

Mandala

Thornton

Milligan

et al. 1998

Journal of Biological Chemistry

110

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Rustmicin is a 14-membered macrolide previously identified as an inhibitor of plant pathogenic fungi by a mechanism that was not defined. We discovered that rustmicin inhibits inositol phosphoceramide synthase, resulting in the accumulation of ceramide and the loss of all of the complex sphingolipids. Rustmicin has potent fungicidal activity against clinically important human pathogens that is correlated with its sphingolipid inhibition. It is especially potent against Cryptococcus neoformans, where it inhibits growth and sphingolipid synthesis at concentrations <1 ng/ml and inhibits the enzyme with an IC 50 of 70 pM. This inhibition of the membrane-bound enzyme is reversible; moreover, rustmicin is nearly equipotent against the solubilized enzyme. Rustmicin was efficacious in a mouse model for cryptococcosis, but it was less active than predicted from its in vitro potency against this pathogen. Stability and drug efflux were identified as two factors limiting rustmicin's activity. In the presence of serum, rustmicin rapidly epimerizes at the C-2 position and is converted to a ␥-lactone, a product that is devoid of activity. Rustmicin was also found to be a remarkably good substrate for the Saccharomyces cerevisiae multidrug efflux pump encoded by PDR5.

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confidence: 99%

Rustmicin, a Potent Antifungal Agent, Inhibits Sphingolipid Synthesis at Inositol Phosphoceramide Synthase

Mandala

Thornton

Milligan

et al. 1998

Journal of Biological Chemistry

110

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“…The molecular target of aureobasidin A [19,20], galbonolide B [21] and rustmicin [22] was specified to IPC synthase [10,23] and khafrefungin was found as its inhibitor [24]. However, their activities were restricted only to yeast-type fungi or phytopathogenic fungi.…”

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confidence: 99%

Pleofungins, Novel Inositol Phosphorylceramide Synthase Inhibitors, from Phoma sp. SANK 13899

Aoyagi

Yano²,

Kozuma³

et al. 2007

J Antibiot

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Pleofungins (formerly called F-15078) A, B, C and D, novel depsipeptide antifungal antibiotics, were found in a mycelium extract of the producing fungus, Phoma sp. SANK 13899. The structures of pleofungins A, B, C and D were elucidated mainly by various NMR studies. The absolute configurations of the amino acids and N-methyl amino acids of pleofungin A constituents in the hydrolysate were determined by the application of advanced Marfey's method in combination with gas chromatography/mass spectrometry analysis of their silylation products with N-methyl-N-(tert-butylsilyl)-trifluoroacetamide. Two a -hydroxy acid constituents, ahydroxyisocaproic acid and a-hydroxyisovaleric acid, were isolated from the hydrolysate and their stereochemistries were determined by their specific rotations.

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“…We have previously reported the isolation of pteridic acids A and B with plant growth promoting activity from the endophytic Streptomyces hygroscopicus TP-A0451 [1]. This strain has been so far identified to produce structurally diverse secondary metabolites; an antifungal prenylated indole [2], a sulfonated linear polyene antibiotic with antifungal activity [3], galbonolides A and B [4,5], elaiophylin [6] and its derivatives, and herbimycins [7] and their hydroquinone congeners. Our continuous search for bioactive compounds from the strain TP-A0451 led to the isolation of pterocidin (1), a new cytotoxic compound.…”

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Pterocidin, a Cytotoxic Compound from the Endophytic Streptomyces hygroscopicus

et al. 2006

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A new cytotoxic compound, pterocidin, was isolated from the endophytic Streptomyces hygroscopicus TP-A0451, and the structure was determined on the basis of spectroscopic data. Pterocidin showed cytotoxicity against some human cancer cell lines with IC 50 values of 2.9ϳ7.1 mM. [6] and its derivatives, and herbimycins [7] and their hydroquinone congeners. Our continuous search for bioactive compounds from the strain TP-A0451 led to the isolation of pterocidin (1), a new cytotoxic compound. We herein describe the isolation and structure elucidation of 1.Ten liters of the culture broth of S. hygroscopicus TP-A0451 were extracted with 1-butanol, and the extract was fractionated on a silica gel column and further subjected to C-18 column chromatography to yield pterocidin (1, 11 mg) as pale yellow oil.The molecular formula of 1 was established to be (Table 1) revealed the presence of signals due to one carbonyl carbon, one oxygenated sp 2 quaternary carbon, nine sp 2 methines, four sp 3 methines adjacent to oxygen atoms, one sp 3 methine, two sp 3 methylenes, three methoxy groups, and two methyls. Since six out of 7 unsaturations were accounted for, 1 was inferred to possess one ring.DQF-COSY spectrum revealed two 1 H-1 H connectivities from H-2 to H-13 branching H-22 at C-12 and from H-15 to H-19. The HMBC correlations for H-15/C-13 and H-15/C-14 suggested the connectivity between C-13 and C-

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Galbonolides A and B - two new non-glycosidic antifungal macrolides from

Cited by 28 publications

References 1 publication

Rustmicin, a Potent Antifungal Agent, Inhibits Sphingolipid Synthesis at Inositol Phosphoceramide Synthase

Rustmicin, a Potent Antifungal Agent, Inhibits Sphingolipid Synthesis at Inositol Phosphoceramide Synthase

Pleofungins, Novel Inositol Phosphorylceramide Synthase Inhibitors, from Phoma sp. SANK 13899

Pterocidin, a Cytotoxic Compound from the Endophytic Streptomyces hygroscopicus

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