Streptomycin antibiotic activity

Before the discovery of streptomycin, pyrazinamide (126) was one of the front runners in the treatment of tuberculosis. A broad spectrum of biological activity has been associated with pyrazine derivatives, ranging from the herbicidal activity of (127) to antibiotic activity... 

Magnesium may reduce the antibiotic activity of streptomycin, tetracycline, and tobramycin when given together. 

Schatz, A. Bugle, E. Waksman, S.A. (1944) Streptomycin, a substance exhibiting antibiotic activity against Gram-positive and Gram-negative bacteria. Proc. Spc. Exp. Biol. Med., 55, 66-9. 

Paromomycin Sulfate, USP. The isolation of paromomycin (Humatin) was reported in I9S6 from a fermentation with a Streptomyces sp. (PD 04998), a strain said to resemble 5. rimostis very closely. The parent organism had been obtained from soil samples collected in Colombia. Paromomycin. however, more closely re.sembles neomycin and streptomycin in antibiotic activity than it dtx s oxytetracycline, die antibiotic obtained from S. rintosus. 

Trihydrochloride monohydrate, CjjH4jNjOu.3HCI.HjO, white, amorphous powder mp 190-200 (corr, decompn) after drying in vacuo at 100°. [ ]g — 47° (c = 1.35 in water). Appears to have about one-fourth of the antibiotic activity of streptomycin tri hydrochloride. 

It has been known for a long time that the removal of both the amidino groups in streptomycin and the acylation of the amino groups destroys the antibiotic activity, whereas the reductive amination, the reduction to dihydrostreptomycin, the monosubstitution of an amidino function by a carbonyl group as in bluensomycin and the demethylation of the N-methylamino group do not affect the effectiveness of streptomycin. The differences in the activity of kanamycin A and B and the neomycins have shown that the number and the position of the amino groups are of importance for their efficacy. 

With the discovery of antibiotics, it became possible for the first time to set up a defence against the causes of this disease. In 1943, Selman A. Waksman discovered streptomycin, an active ingredient of the mould Streptomyces griseus this shows exceptionally good artivity against the tuberculosis-causing bacteria, and its use provided the means to combat the disease. 

The V-methyl derivative of L-glucosamine (the enantiomorph of the common D-glucosamine) has been isolated from the degradation product of streptomycin 259). It is interesting to speculate that the antibiotic activity of the streptomycin may arise from the presence of the L-form of the glucosamine. 

Many other antibiotic compounds have also been isolated from the genus Streptomyces, all of which are closely related in structure to streptomycin. Six of them are currently in use in the United States kanamycin, neomycin, paromomycin, gentamicin, tobramycin, and netilmicin. All of these compounds exhibit at least one aminohexose in their structure, and extensive research on the relationship between structure and activity indicates that at least one amino sugar is necessary for antibiotic activity. As shown, kanamycin and neomycin both contain two amino sugars. 

The effects must be evident for the antibiotically active forms of streptomycin but show no reaction with those derivatives of streptomycin which have no antibiotic activity. 

In 1939 the isolation of a mixture of microbial products named tyrotbricin from a soil bacillus was described. Further investigation showed this material to be a mixture of gramicidin and tyrocidine. In rapid succession the isolation of actinomycin (1940), streptothricin (1942), streptomycin (1943), and neomycin (1949), produced by Streptomjces were reported and in 1942 the word antibiotic was introduced. Chloramphenicol, the first of the so-called broad spectmm antibiotics having a wide range of antimicrobial activity, was discovered in 1947. Aureomycin, the first member of the commercially important tetracycline antibiotics, was discovered in 1948. 

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