Tirandalydigin, a novel tetramic acid of the tirandamycin-streptolydigin type. I. Taxonomy of the producing organism, fermentation and biological activity.

Tirandalydigin is a new tetramic acid antibiotic which was discovered in a screen designed to find compounds with activity against pathogenic anaerobic bacteria. It was named tirandalydigin because it possesses structural features that are common to both tirandamycin and streptolydigin. The producing culture, strain AB 1006A-9, is a Streptomyces and was compared to the streptomycetes that synthesize tirandamycin and streptolydigin. It is closely related to the former culture and was named Streptomyces tirandis subsp. umidus. Tirandalydigin has MICs in the range of 0.5 to 32 micrograms/ml against many pathogenic anaerobes, streptococci, enterococci and legionellae.

Dunaimycins, a new complex of spiroketal 24-membered macrolides with immunosuppressive activity. I. Taxonomy of the producing organisms, fermentation and antimicrobial activity.

The dunaimycins are a new complex of spiroketal 24-membered macrolides discovered in the fermentation broth of two actinomycetes. Based on taxonomic studies these two cultures, which were isolated from soil, were identified as Streptomyces diastatochromogenes strains AB 1691Q-321 and AB 1711J-452. The dunaimycins possess both immunosuppressive and antimicrobial activity.

Aselacins, novel compounds that inhibit binding of endothelin to its receptor. I. The producing organism, fermentation and biological activity.

A radioligand test to detect inhibitors of endothelin-1 binding to its receptors in bovine atrial and porcine cerebral membranes was used to screen fungal metabolites from stationary fermentations. Inhibitory activity, observed in culture extracts of two Acremonium species, led to the discovery of aselacins A, B and C. Aselacin A inhibits binding to both membrane fractions with IC50s of approximately 20 micrograms/ml.

Coumamidines, new broad spectrum antibiotics of the cinodine type. I. Discovery, taxonomy of the producing organism and fermentation.

Coumamidines are water-soluble basic antibiotics related to the glycocinnamoylspermidines. They are produced by a soil isolate designated Saccharopolyspora sp. AB 1167L-65. The coumamidines have broad spectrum activity and were selected in a screen for substances which inhibit Pseudomonas aeruginosa.

Calbistrins, novel antifungal agents produced by Penicillium restrictum. I. Production, taxonomy of the producing organism and biological activity.

A novel antibiotic complex, named the calbistrins, has been discovered in the culture broth of a soil fungus. The producing organism, designated AB 1875C-28, was identified as a strain of Penicillium restrictum. Calbistrin A, the most potent of the 4-membered complex, has MICs of 0.78 micrograms/ml against Candida albicans. Only poor activity is observed against non-candida yeasts, filamentous fungi and bacteria.

5-N-acetylardeemin, a novel heterocyclic compound which reverses multiple drug resistance in tumor cells. I. Taxonomy and fermentation of the producing organism and biological activity.

The ardeemins are a new family of secondary metabolites produced by submerged fermentation of a fungus which was isolated from a soil sample collected in Brazil. Based on taxonomic studies, the producing culture was identified as Aspergillus fischeri var. brasiliensis strain AB 1826M-35. 5-N-Acetylardeemin potentiated the cytotoxicity of the anticancer agent vinblastine in multidrug resistant human tumor cells.

Fusacandins A and B; novel antifungal antibiotics of the papulacandin class from Fusarium sambucinum. I. Identity of the producing organism, fermentation and biological activity.

The fuscandins, antifungal agents of the papulacandin class, are produced by a strain of Fusarium sambucinum. Fermentation yielded 60 mg/liter of fusacandin A and minor amounts of fusacandin B. As expected, the fusacandins inhibit (1,3)-beta-glucan synthesis. Fusacandin A is slightly less active than papulacandin B against Candida albicans and, like papulacandin, loses activity in the presence of serum.

Macquarimicins, microbial metabolites from Micromonospora. I. Discovery, taxonomy, fermentation and biological properties.

A novel series of microbial metabolites were discovered in fermentation broths of two soil isolates. Both cultures were identified as strains of Micromonospora chalcea. Production of the metabolites, named macquarimicins, was monitored by an HPLC assay. A seven-day fermentation yielded 27 mg/liter of macquarimicin A. With MICs of 50 to 100 micrograms/ml, macquarimicin A has only very low activity against strains of Bacteroides and other anaerobes. Macquarimicin B has inhibitory activity against the leukemia cell line P-388.

Novel triterpene sulfates from Fusarium compactum using a rhinovirus 3C protease inhibitor screen.

Two novel triterpene sulfates have been isolated from Fusarium compactum by bioactivity-directed fractionation using an assay which measures the inhibition of proteolytic activity of rhinovirus 3C protease on a fluorogenic peptide substrate. The compounds were purified by countercurrent and reverse phase chromatographies. NMR, MS, UV and IR studies revealed two triterpene sulfates, uncommon metabolites of terrestrial fungi.

Dibefurin, a novel fungal metabolite inhibiting calcineurin phosphatase activity.

The novel calcineurin inhibitor, dibefurin, has been isolated from the fungal culture AB 1650I-759. The isolation was bioactivity-directed fractionation using an assay which measures the phosphatase activity of calcineurin. The compound was purified by countercurrent, reverse phase and gel filtration chromatographies. Several studies, including crystallographic, NMR and MS, revealed that dibefurin is a novel dimeric compound of a unique structural type.

Gas chromatographic-mass spectrometric identification and quantitation of benzyl alcohol in serum after derivatization with perfluorooctanoyl chloride: a new derivative.

Benzyl alcohol is commonly used as an antibacterial agent in a variety of pharmaceutical formulations. Several fatalities in neonates have been linked to benzyl alcohol poisoning. Most methods for measuring benzyl alcohol concentrations in serum utilize direct extraction followed by high-performance liquid chromatography. We describe here a novel derivatization of benzyl alcohol using perfluorooctanoyl chloride after extraction from human serum for analysis by gas chromatography-mass spectrometry (GC-MS). The derivative was eluted at a significantly higher temperature respective to underivatized molecule and the method was free from interferences from more volatile components in serum and hemolyzed specimens. Another advantage of this derivatization technique is the conversion of low-molecular-mass benzyl alcohol (Mr 108) to a high-molecular-mass derivative (Mr 504). The positive identification of benzyl alcohol can be achieved by observing a distinct molecular ion at m/z 504 as well as the base peak at m/z 91. Quantitation of benzyl alcohol in human serum can easily be achieved by using 3,4-dimethylphenol as an internal standard. The within run and between run precisions (using serum standard of benzyl alcohol: 25 mg/l) were 2.7% (mean=24.1, S.D.=0.66 mg/l, n = 8) and 4.2% (mean=24.3, S.D.=1.03 mg/l, n = 8), respectively. The assay was linear for the serum benzyl alcohol concentrations of 2 mg/l to 200 mg/l and the detection limit was 0.1 mg/l. We observed no carry-over (memory effect) problem in our assay as when 2 microl ethyl acetate was injected into the GC-MS system after analyzing serum specimens containing 200 mg/l of benzyl alcohol, we observed no peak for either benzyl alcohol or the internal standard in the total ion chromatogram.