RESUMEN
The strain Streptomyces roseoflavus INA-1278 is described as a new irumamicin producer. Irumamicin 1278 is different by the antifungal activity from irumamicin produced by the world-known strain Streptomyces subflavus subsp. Irumaensis subps. nov. AM-3603.
Asunto(s)
Antifúngicos/aislamiento & purificación , Antifúngicos/farmacología , Macrólidos/aislamiento & purificación , Macrólidos/farmacología , Streptomyces/crecimiento & desarrollo , Streptomyces/metabolismo , Aspergillus niger/efectos de los fármacos , Bacillus subtilis/efectos de los fármacos , Candida albicans/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Pruebas de Sensibilidad MicrobianaRESUMEN
Antimicrobial activity of partial degradation products of eremomycin, a new glycopeptide antibiotic, was studied. The products formed by eremomycin deglycosylation (deseremosaminyl eremomycin, eremosaminyl aglycone and aglycone) and elimination of the chlorine atom from the molecule aglycone moiety (dechloroeremomycin). The spectral data in favour of the compounds structure are presented. It was found that partial degradation led to a decrease in the antimicrobial activity of the antibiotic. Dechloreremomycin had the highest activity among the products. Its MIC for the methicillin-resistant strains of Staphylococcus aureus was only twice as low as that of the initial antibiotic.
Asunto(s)
Antibacterianos , Antibacterianos/química , Antibacterianos/análisis , Antibacterianos/metabolismo , Antibacterianos/farmacología , Bacillus subtilis/efectos de los fármacos , Cromatografía Líquida de Alta Presión , Glicopéptidos/análisis , Glicopéptidos/química , Glicopéptidos/metabolismo , Glicopéptidos/farmacología , Espectroscopía de Resonancia Magnética , Espectrometría de Masas , Pruebas de Sensibilidad Microbiana , Staphylococcus aureus/efectos de los fármacos , Relación Estructura-ActividadRESUMEN
Derivatives of antitumour anthracycline antibiotics containing N-methylurea moiety in the carbohydrate ring were obtained by the interaction of methyl isocyanate with daunorubicin, doxorubicin, carminomycin and daunorubicin derivatives, substituted at C-13 or C-14 positions. N-Nitrosation of these compounds yielded modified anthracycline antibiotics containing the N-methyl-N-nitrosourea substituent at C-3' position. Alkaline degradation of these derivatives produced, through corresponding isocyanates cyclic 3'-N,4'-carbonylderivatives. In these anthracycline derivatives with sugar cycles conjugated with oxazoline-2-ones the predominant conformations of sugar ring has changed from 1C4 to 4C1, 2,5B, or B0,3 (shown by 1H NMR spectroscopy). It was demonstrated, both in vitro and in vivo, that introduction of methylurea or cytotoxic methylnitrosourea moieties does not potentiate antimicrobial, cytotoxic or antitumour properties of these compounds.
Asunto(s)
Antibióticos Antineoplásicos/síntesis química , Daunorrubicina/síntesis química , Leucemia P388/tratamiento farmacológico , Leucemia Experimental/tratamiento farmacológico , Metilnitrosourea/síntesis química , Compuestos de Metilurea/síntesis química , Animales , División Celular/efectos de los fármacos , Fenómenos Químicos , Química , Daunorrubicina/farmacología , Masculino , Ratones , Relación Estructura-ActividadRESUMEN
Possible modification of eremomycin, a novel glycopeptide antibiotic by the amine groups with acylating agents such as Ac2O/MeOH and CH3(CH2)7COCl/Et3N and alkylating agents such as CH3CHO, NaBH and NaBH3CN was studied. N-Acetyl, N,N'-diacetyl. N-pelargoil, N-ethyl, N,N'-diethyl and N,N',N"-triethyl derivatives of eremomycin were prepared. Their structure was asserted and the order of the substitute introduction was determined. The antimicrobial activity against Bacillus subtilis and Staphylococcus aureus was assayed. It was found that with introduction of the ethyl substitutes to the eremomycin molecule the antibiotic activity lowered insignificantly whereas the acylation resulted in its decreasing by 1-2 orders.