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Biomedical subjects

J Clardy

Publications and source records attributed to J Clardy.

At least 91 records · Page 5Linked to original sources

Karnamicin, a complex of new antifungal antibiotics. I. Taxonomy, fermentation, isolation and physico-chemical and biological properties.

A complex of new antifungal antibiotics designated karnamicin was isolated from the cultured broth of Saccharothrix aerocolonigenes No. N806-4. Fifteen components have so far been isolated from the complex; the major component karnamicin B2 was identified by X-ray crystallography to be a novel molecule unrelated to known antibiotics. All components of karnamicin exhibited a rather broad spectrum of activity against fungi and yeasts with MICs ranging from 3.1 to 50 micrograms/ml.

Actinomycetales↗

Phytotoxins from the pathogenic fungi Drechslera maydis and Drechslera sorghicola.

Drechslera maydis, the causal agent of Southern corn leaf blight, and Drechslera sorghicola, the causal agent of leaf spot on Johnson grass, produce a series of phytotoxic sesterterpenoids. These sesterterpenoids belong to the ophiobolin family. One of them, ophiobolin I, was characterized by x-ray diffraction and served as a crucial reference compound for characterizing four other ophiobolins. All of the ophiobolins studied produce characteristic lesions on host plants at concentrations of 1 mM to 1 muM. The ophiobolin characterized as 6-epiophiobolin A is selectively toxic to corn bearing Texas-male-sterile (Tms) cytoplasm when assayed in a dark CO(2) fixation assay. It is plausible that these ophiobolins had a role in the 1970 corn-blight epidemic in North America.

Journal Article↗

The pseudopterosins: anti-inflammatory and analgesic natural products from the sea whip Pseudopterogorgia elisabethae.

The Caribbean sea whip Pseudopterogorgia elisabethae (Octocorallia, Cnidaria) has been found to contain the pseudopterosins, a newly described class of natural products, which have been characterized as diterpene-pentoseglycosides. The pseudopterosins possess anti-inflammatory and analgesic properties that exceed, in our assays, the potencies of existing drugs such as indomethacin. As anti-inflammatory agents, the pseudopterosins appear to modify the arachidonic acid cascade by an as yet undefined mechanism of pharmacological action.

Animals↗

PD 116,152, a new phenazine antitumor antibiotic. Structure and antitumor activity.

A new, highly substituted phenazine with antitumor activity was isolated from the culture broth of a Streptomyces sp. This compound, whose structure was determined by spectroscopic methods and verified by X-ray diffraction analysis, was found to be methyl 6-formyl-4,7,9-trihydroxy-8-methyl-1-phenazinecarboxylate.

Antibiotics, Antineoplastic↗

Bipolaroxin, a selective phytotoxin produced by Bipolaris cynodontis.

Two sesquiterpenes have been isolated from the fungal pathogen of Bermuda grass Bipolaris cynodontis. Chemical, spectral, and x-ray diffraction studies have led to the characterization of these as bipolaroxin and dihydrobipolaroxin, highly oxygenated members of the eremophilane family. Bipolaroxin is phytotoxic to some but not all of the plants tested. To our knowledge, a phytotoxin with host selectivity isolated from a weed pathogen has not been reported previously.

Fungi↗

Alteichin: an unusual phytotoxin from Alternaria eichorniae, a fungal pathogen of water hyacinth.

The phytopathogenic fungus Alternaria eichorniae attacks water hyacinth, an economically significant aquatic weed. The novel phytotoxin alteichin was isolated from liquid cultures of this fungus and its structure was deduced by X-ray crystallographic analysis. Altheichin is a doubly hydrated form of 4,9-dihydroxy perylene-3, 10-quinone. A single step dehydration of alteichin to anhydroalteichin is catalyzed both by acid and by a crude enzyme preparation from water hyacinth.

Alternaria↗

A new naphthaquinone antibiotic from a new species of yeast.

A fusiform yeast producing limited pseudomycelium and limited true mycelium on malt extract agar has been isolated. This non-fermentative yeast has hyaline cell walls but produces a thick, black oily exudate which is water insoluble and gives the colony a smooth black lacquered appearance. On the basis of morphology and physiology, this organism is distinctive enough to warrant the designation of a new genus. During stationary phase of cultures on chemically defined medium, a deep red substance is produced which has strong antibiotic activity against Staphylococcus aureus in vitro. The substance has been identified as a new natural naphthaquinone of the empirical formula C16H16O7 .

Anti-Bacterial Agents↗

Absolute stereochemistry and dopaminergic activity of enantiomers of 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine.

Resolution of the unique dopamine receptor agonist 2,3,4,5-tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-benzazepine (1) was achieved by a stereospecific multistep conversion of the readily separated enantiomers of its O,O,N-trimethylated precursor 2. The absolute stereochemistry of the antipodes of 2-MeI was determined by single-crystal X-ray diffractometric analysis, thus permitting assignment of the configuration of stereospecifically related 1, as well as that of the synthetic intermediates. High-performance liquid chromatography of diastereoisomeric derivatives was utilized to determine the enantiomeric excess of the R (greater than 97%) and S (greater than 89%) isomers of 1. Examination of the isomers in several in vitro and in vivo tests for both central and peripheral dopaminergic activity revealed that activity resided almost exclusively in the R isomer. The results suggest that the properly oriented 1-phenyl substituent of 1 is important for dopamine-like activity; it may contribute to receptor binding by interaction with a chirally defined accessory site. Configurational and conformational requirements for receptor binding of 1 are considered in relationship to previously described dopaminergic agents. These studies, in accord with previous suggestions, indicate that (R)-1 interacts with dopamine receptors in a conformation in which the catecholic hydroxyls and basic nitrogen are at least nearly maximally separated.

2,3,4,5-Tetrahydro-7,8-dihydroxy-1-phenyl-1H-3-ben↗

Fluoroprostaglandins: synthesis and biological evaluation of the methyl esters of (+)-12-fluoro-, (-)-ent-12-fluoro-, (+)-15-epi-fluoro-, and (-)-ent-15 epi-12-fluoroprostaglandin F2 alpha.

The synthesis and biological activity of the methyl esters of (+)-12-fluoroPGF2 alpha, (+)-15-epi-12-fluoroPGF2 alpha, (-)-ent-12-flurorPGF2 alpha, and (-)-ent-15-epi-12-fluoroPGF2 alpha are described. Each fluoroprostaglandin has been evaluated from pregnancy interruption in the hamster and smooth-muscle stimulating effects on gerbil colon and hamster uterine strips. All fluoroprostaglandins synthesized were shown to be neither substrates for the 15-hydroxyprostaglandin dehydrogenase nor inhibitors of the enzyme.

Abortifacient Agents, Nonsteroidal↗

Brasilenyne and cis-dihydrorhodophytin: Antifeedant medium-ring haloethers from a sea hare (Aplysia brasiliana).

Two straight-chain C(15) fish antifeedants have been isolated from the sea hare Aplysia brasiliana. Chemical, spectral, and x-ray diffraction studies led to the characterization of these medium-ring ethers as brasilenyne (2) and cis-dihydrorhodophytin (3). The oxonin ring system of 2 is novel in nature. Biosynthetic considerations permit the postulation that a third compound, a noncrystalline congener of these compounds, is cis-isodihydrohodophytin (4).

Journal Article↗

Mycotoxins produced by Aspergillus fumigatus isolated from silage.

Results are presented which show that Aspergillus fumigatus was one of the predominant fungi contaminating moldy silage. Growth of A. fumigatus on silage appeared to depend on a preliminary aerobic fermentation by other natural microflora in silage. The clavine alkaloid, fumigaclavine A, and a new clavine alkaloid designated fumigaclavine C were produced by A. fumigatus. The LD50 of fumigaclavine C was approximately 150 mg/kg oral dose in day-old cockerels.

Animal Feed↗