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J Antibiot (Tokyo) ; 28(8): 580-9, 1975 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-1158783

RESUMEN

The chemical dimers of rifamycin SV resembled the corresponding monomeric analogs with respect to the inhibitory properties versus the nucleic acid polymerases. At low doses, such compounds blocked the initiation step of the DNA transcription catalyzed by the bacterial RNA polymerase, as observed for the parental antibiotic and its derivative rifampicin which are largely used in therapy. At concentrations one to two orders of magnitude higher, the chemically modified rifamycins inhibited also other nucleotidyltransferases. The widespread toxicity of the dimeric and monomeric semisynthetic rifamycins versus these enzymes was not causally related with an enhancement of their lipophily. The observed effects might be due to a loss of selectivity in the inhibition mechanism which was originally specific for the RNA polymerase from E. coli at the beginning of its catalysis. The rifamycin derivatives might then react with the catalytic portion of other nucleotidyltransferases interfering adversely with the enzyme activity in a number of ways and/or at different levels.


Asunto(s)
ADN Nucleotidiltransferasas/antagonistas & inhibidores , ARN Polimerasas Dirigidas por ADN/antagonistas & inhibidores , Rifamicinas/toxicidad , Animales , Bovinos , Fenómenos Químicos , Química , ADN/biosíntesis , ADN Bacteriano/biosíntesis , ARN/metabolismo , ARN Bacteriano/metabolismo , Rifampin/toxicidad
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