Streptomycinic acid

Fried and Wintersteiner - oxidized streptomycin trihydrochloride with bromine water to an amorphous, antibiotically inactive product The relatively strongly acidic nature of this substance, which they named streptomycinic acid, was demonstrated by electrometric titration. In the infrared spectral region the substance exhibited an absorption maximum at a wave length of 6.06m, which was partially displaced to 5.81m when the spectrum was observed in the presence of deuterium oxide and deuterium chloride. A shift of this type is usually found with dipolar ions and was taken therefore as an indication of the expected dipolar ion character of streptomycinic acid. 

Serum albumin is the most abundant plasma protein (3.5-5.5%) and is responsible for the binding and transport of various metabolically and pharmacologically active molecules, e.g., bilirubin, uric acid, vitamin C, acetylcholine, cholinesterase, adenosine, aureomycin, barbiturate, Chloromycetin, digitonin, fatty acids, atabrine, neosilversalvarsan, penicillin, salicylate,/ -aminosalicylate, sulfonamide, streptomycin, acid dyes, histamine, triiodothyronine, and thyroxine (Bennhold, 1962 Putnam, 1975). Moreover, albumin tightly binds various metal ions, e.g., Zn (Giroux,... 

Substitution of an amino group into the molecule affords an iigent with antibacterial activity. Although seldom used alone, l, ira- aminosalicylic acid (PAS, 7) has been employed as an adjunct Id streptomycin and isoniazid in treatment of tuberculosis. 

Drugs can also Interfere with laboratory results by negating certain nonspecific oxidation and reduction reactions essential for the chemical assay. Penicillin, streptomycin and ascorbic acid are known to react with cupric Ion thus, false positive results for glucose may occur If a copper reduction method Is used. If the specific enzymatic glucose-oxidase method Is employed, ascorbic acid can cause a false negative result by preventing the oxidation of a specific chromogen In the reaction. 

Stiepton dn was isolated by Waksman in 1944, and its activity against M tuberculosis ensured its use as a primaiy ding in the treatment of tuberculosis. Unfortunately, its ototoxicity and the rapid development of resistance have tended to modify its usefulness, and although it still remains a front-hne dmg against tuberculosis it is usually used in combination with isoniazid and p(4)-aminosalicyhc acid (section 11.5). Streptomycin also shows activity against other types of bacteria,... 

The three standard drugs used in the treatment of tuberculosis were streptomycin (considered above), -aminosalicylic acid (PAS) and isoniazid (isonicotinylhydrazide, INH synonym, isonicotinic acid hydrazine, INAH). The tubercle bacillus rapidly becomes resistant to streptomycin, and the role of PAS was mainly that of preventing this development of resistance. The current approach is to treat tuberculosis in two phases an initial phase where a combination of three dmgs is used to reduce the bacterial level as rapidly as possible, and a continuation phase in which a combination of... 

Studies on the hydrolytic inactivation of hydroxystreptomycin have shown that this compound is remarkably more stable under acidic conditions than is streptomycin.64... 

The cell-bound amylopullulanase was solubilized with detergent and lipase. It was then purified to homogeneity by treatment with streptomycin sulfate and ammonium sulfate, and by DEAE-Sephacel, octyl-Sepharose and puUulan-Sepharose column chromatography (12). The final enzyme solution was purified 3511-fold over the crude enzyme extract with an overall recovery of 42% and had a specific activity of 481 units/mg protein. The average molecular weight of the enzyme was 136,500 determined by gel filtration on Sephacryl S-200 and SDS-PAGE, and it had an isoelectric point at pH 5.9. It was rich in acidic and hydrophobic amino acids. The purified enzyme was quite thermostable in the absence of substrate even up to 90°C with essentially no loss of activity in 30 min. However, the enzyme lost about 40% of its original activity at 95 C tested for 30 min. The optimum tenq)erature for the action of the purified enzyme on pullulan was 90°C. However, the enzyme activity rapidly decreased on incubation at 95°C to only 38% of the maximal 30 min. The enzyme was stable at pH 3.0-5.0 and was optimally active at pH 5.5. It produced only maltotriose and no panose or isopanose from pullulan. 

Drugs of choice are isoniazid, rifampin, ethambutol, along with streptomycin and pyrazinamide. Less well tolerated, second-line agents include p-aminosal-icylic acid, cycloserine, viomycin, ka-namycin, amikacin, capreomycin, ethionamide. 

Aminosalicylic acid is a bacteriostatic that inhibits most tuberculous mycobacteria, hi terms of tuberculostatic activity it is inferior to isoniazid and streptomycin. It is nephro-and hepatotoxic, and is rarely used. A synonym of this drug is apacizin. 

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