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1.
J Antibiot (Tokyo) ; 49(2): 119-23, 1996 Feb.
Article in English | MEDLINE | ID: mdl-8621349

ABSTRACT

Cytosporin A, B and C, three antagonists of [125I]-angiotensin II binding to rat adrenal glands were discovered in fermentations of an endophytic Cytospora sp. during routine screening using semi-automated procedures. The most potent of these displayed an IC50 of 1.5-3 microM and was specific for angiotensin II AT2.


Subject(s)
Angiotensin II/antagonists & inhibitors , Benzopyrans/pharmacology , Mitosporic Fungi/chemistry , Adrenal Glands/metabolism , Angiotensin II/metabolism , Animals , Benzopyrans/chemistry , Fermentation , Mass Spectrometry , Rats
2.
J Antibiot (Tokyo) ; 37(9): 970-5, 1984 Sep.
Article in English | MEDLINE | ID: mdl-6094416

ABSTRACT

The maximum yield for the production of L-681,110 by Streptomyces sp. MA-5038 (ATCC 31587) was observed after 5 days' incubation at 28 degrees C and pH about 8.3. L-681,110 was isolated from the fermentation broth by acetone extraction of the mycelia, absorption to Amberlite XAD-2 resin and two separations by thin-layer chromatography. The structure of L-681,110 was found to consist of a sixteen-membered lactone with a new type of substitution. The inhibition of ATPase, activity against Caenorhabditis elegans and stimulation of gamma-aminobutyric acid release indicate that L-681,110 possesses some characteristics of both oligomycin and avermectin. L-681,110 was also active against tapeworm and ticks in an in vivo assay.


Subject(s)
Lactones/isolation & purification , Sodium-Potassium-Exchanging ATPase/antagonists & inhibitors , Streptomyces/metabolism , Animals , Brain/drug effects , Caenorhabditis/drug effects , Cestoda/drug effects , Fermentation , Guinea Pigs , In Vitro Techniques , Lactones/pharmacology , Male , Rats , Ticks/drug effects , gamma-Aminobutyric Acid/metabolism
3.
J Antibiot (Tokyo) ; 37(5): 462-5, 1984 May.
Article in English | MEDLINE | ID: mdl-6203886

ABSTRACT

L-681,176, an inhibitor of angiotensin converting enzyme was found in the culture filtrate of Streptomyces sp. MA 5143. The I50 of the crystalline inhibitor is about 1.3 micrograms/ml and the inhibition is reversed by zinc sulfate. In rats, L-681,176 exhibits a dose-related inhibition of the pressor response to angiotensin I with an ID50 of 142 mg/kg when administered intravenously. The structure of L-681,176 is similar to that of marasmine but lacking one carboxyl group. The maximum yield of L-681,176 occurs after three to four days growth at 28 degrees C.


Subject(s)
Angiotensin-Converting Enzyme Inhibitors , Guanidines/isolation & purification , Oligopeptides/isolation & purification , Streptomyces/metabolism , Animals , Blood Pressure/drug effects , Guanidines/pharmacology , In Vitro Techniques , Oligopeptides/pharmacology , Rats , Teprotide
4.
Antimicrob Agents Chemother ; 15(3): 361-7, 1979 Mar.
Article in English | MEDLINE | ID: mdl-464561

ABSTRACT

The avermectins are a complex of chemically related agents which exhibit extraordinarily potent anthelmintic activity. They are produced by a novel species of actinomycete, NRRL 8165, which we have named Streptomyces avermitilis. The morphological and cultural characteristics which differentiate the producing organism from other species are described. The avermectins have been identified as a series of macrocyclic lactone derivatives which, in contrast to the macrolide or polyene antibiotics, lack significant antibacterial or antifungal activity. The avermectin complex is fully active against the gastrointestinal nematode Nematospiroides dubius when fed to infected mice for 6 days at 0.0002% of the diet. Fermentation development, including medium modification and strain selection, resulted in increasing the broth yields from 9 to 500 mug/ml.


Subject(s)
Anthelmintics/metabolism , Lactones/metabolism , Streptomyces/metabolism , Anthelmintics/analysis , Disaccharides/metabolism , Fermentation , Ivermectin/analogs & derivatives , Streptomyces/classification , Streptomyces/isolation & purification , Time Factors
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