Estreptomicina: propiedades fisicoquímicas y toxicidad vestibular / Streptomycin, physical and chemical characteristics and vestibular toxicity

Propósito: Los antibióticos aminoglucósidos estreptomicina (STP) y kanamicina (KAN) son tóxicos para las células sensoriales del vestíbulo y de la cóclea, respectivamente. Químicamente están constituidos por estreptidina (STD) un derivado del inositol y dos azúcares, la esteptosa (Stosa) y la N-metilglucosamida (nm-GLUN); sin embargo, en la STP, la STD tiene dos sustituyentes guanidino, los que están ausentes en la KAN. Por lo tanto, se propone estudiar si la vestíbulo-toxicidad específica de la STP se debe a los grupos guanidino. Material y Métodos: Se incubaron en vitro, membranas celulares aisladas de los órganos vestibulares, con 3H-espermidina (3H-Spdina), un análogo estructural de la STP. Se midió la capacidad de los siguientes compuestos: STP, STD, KAN, guanidina (GUA) y n-acetilglucosamina (na-GLUN) para desplazarlos específicamente. Resultados: Se encontró que el orden de desplazamiento de la 3HSPdina para esas sustancia era STP=STD KanGUAn-a-GLUN. Conclusiones: Los resultados sugieren fuertemente que la STP debe su especificidad vestibulotóxica, a la presencia de los grupos guanidino en la porción de STD de su molécula, los que interactuarían por sus cargas positivas con estructuras membranales vestibulares relacionadas con la transducción, muy probablemente los cilios sensorios de las células ciliadas vestibulares

Synthesis of active nitroguaiacol ether derivatives of streptomycin.

The synthesis, purification, and biological properties of nitroguaiacol ether derivatives of streptomycin and their corresponding radioactive reduced products were examined. These derivatives are biologically active against gram-positive and gram-negative eubacteria and they are also photoreactive because of the presence of the nitroguaiacol group in the molecule. We demonstrated that these derivatives can be used as streptomycin analogs in photoaffinity labeling of the macromolecular structures related to the mode of action of the antibiotic.

Streptomycylamines: difference in activity and mode of action between short-chain and long-chain derivatives.

A homologue series of aliphatic streptomycylamines (SM-amines) have been prepared and tested in vitro (binding to 70S ribosomes) and in vivo (MIC). The short-chain SM-amines act as streptomycin (SM) but are less active than SM. They are inactive towards a SM-resistant Escherichia coli, our strain 042. The long-chain SM-amines are active both towards our sensitive and resistant E. coli, our strains 079 and 042. Their activities are not pH-dependent in contrast to that of SM. However, the higher homologues of the aliphatic amines (C10 Congruent TO C10) are considerably active per se although two to four times less than the corresponding SM-amines. Further, the amines do not compete with the SM-amine for the binding to the ribosomal particles. The binding affinities of these long-chain SM-amines to ribosomes are considerably smaller than that of SM. The binding is however specific as a typical isotope dilution curve can be obtained. We conclude that the long-chain SM-amines have a mode of action different from that of SM.