Antibiotics chloramphenicol

Yamanaka et al. [37] described the influence of bioactive organic agents such as nalidixic acid and chloramphenicol (antibiotics) as well as dithio-threitol (a reducing reagent) as additives to the BC culture medium. In this case, not only the crystallization of the fibers and the material properties are influenced but the Gluconacetobacter cells are themselves also changed. 

In the course of U.S. Senate sub-committee hearings on drug pricing and equivalence of generics late 1967, it developed that different commercial preparations of chloramphenicol antibiotic, all of which conformed with specifications of the U.S. Pharmacopeia and the regulations of the FDA, were not therapeutically equivalent. One brand showed more rapid absorption and plasma-level build-up, a critical difference. As a sequel, competitive brands were temporarily withdrawn from sale while the FDA and a joint National Formulary-USP panel undertook a review of test procedures. 

Petrescu D, Marca G, Veronese M (1972) Humoral antibody production following primary and secondary immunization in rabbits treated with thiamphenicol and chloramphenicol. Antibiot Chemother 17 200-216... 

In pharmaceutical appHcations, the selectivity of sodium borohydride is ideally suited for conversion of high value iatermediates, such as steroids (qv), ia multistep syntheses. It is used ia the manufacture of a broad spectmm of products such as analgesics, antiarthritics, antibiotics (qv), prostaglandins (qv), and central nervous system suppressants. Typical examples of commercial aldehyde reductions are found ia the manufacture of vitamin A (29) (see Vitamins) and dihydrostreptomycia (30). An acyl azide is reduced ia the synthesis of the antibiotic chloramphenicol (31) and a carbon—carbon double bond is reduced ia an iatermediate ia the manufacture of the analgesic Talwia (32). 

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. 

Veterinary Potential or Fiorfenicol. The absolute ban on the use of chloramphenicol ia food producing animals ia the United States and Canada has accentuated the need for an effective broad spectmm antibiotic ia animal food medicine. Fiorfenicol and other antibiotics commonly used ia veterinary medicine have been evaluated in vitro against a variety of important veterinary and aquaculture pathogens. Some of these data ate shown in Tables 4 and 5, respectively. Fiorfenicol was broadly active having MICs lower than those of chloramphenicol in each of the genera tested (Table 4). Florfenicol was also superior to chloramphenicol, thiamphenicol, oxytetracycline [79-57-2] ampicillin [69-53-4] and oxolinic acid [14698-29-4] against the most commonly isolated bacterial pathogen of fish in Japan (Table 5) (37). 

Some antibiotics, such as the tetracyclines, tetracycline (7), doxycycline (78), and minocycline (17), chloramphenicol (79), and clindamycin (23) have modest antimalarial properties, but are slow-acting. 

In order to prevent veterinary dmgs from being transported to the human food chain, radioisotopic immunoassays were developed to monitor veterinary antibiotics such as penicillin and chloramphenicol [56-75-7] C22H22Cl2N20, in meat, milk, and eggs (qv) (see ANTIBIOTICS Meatproducts Milk AND MILKPRODUCTS). 

In recent years, many parent dmgs have been converted to esters to generate so-called prodmgs ia order to overcome some undesirable property such as bitter taste, poor absorption, poor solubiUty, and irritation at site of iajection. For example, antibiotics such as chloramphenicol [56-75-7] and clindamycin [18323-44-9] have been derivatized as their palmitate esters ia order to minimise their bitter taste. 

Antibiotics such as penicillin, streptomycin, tetracyclines, chloramphenicol, and antifungals ... 

The thiophene analog of chloramphenicol (255) has been synthesized,as also have been similar structures. The antibacterial activity of all was much lower than that of the natural antibiotic. The thioamide of 2-thenoic acid has been prepared in a study of potential antitubercular compounds. It did not surpass thioisonico-tinamide in antitubercular activity. The thiosemicarbazones of thio-phenealdehydes and ketones (cf. Section VII,D) show high activity against Mycobacterium tuberculosis, but are very toxic. The thiosemi-carbazone of 4-(2-thienyl)-3-buten-2-one has been reported to be capable of completely inhibiting the in vitro growth of M. tuberculosis even in relatively low concentrations. ... 

Chloramphenicol, a powerful antibiotic isolated in 1949 from the Streptomyces venezuelae bacterium, is active against a broad spectrum of bacterial infections and is particularly valuable against typhoid fever. Assign R,S configurations to the chirality centers in chloramphenicol. 

This is by far the most versatile route to the synthesis of ester-substituted aziridines, especially as the benzhydryl group can easily be cleaved by hydrogenolysis. Wulff has applied this methodology to a short asymmetric synthesis of the antibiotic (-)-chloramphenicol in four steps from p-nitrobenzaldehyde (Scheme 1.34) [61]. In this case it was found that treatment of the aziridine 111 with excess dichloroacetic acid gave the hydroxy acetamide directly, so no separate deprotection step was required. 

The preferred substrates of acetyltransferases are amino-groups of antibiotics, like chloramphenicol, strepto-gramin derivatives, and the various aminoglycosides. The modification is believed to block a functional group involved in the drug-target-interaction. All acetyltransferases use acetyl-coenzyme A as cofactor. 

Acetyl-CoA is also utilized as a cofactor to modify chloramphenicol by O-acetyltranferases (CATs). These enzymes have been found in many different bacterial genera and are usually plasmid encoded in clinical isolates. Furthermore, streptogramin type A antibiotics are acetylatedby Vat enzymes that occur on plasmids in staphylococci and enterococci. 

Ribosomal Protein Synthesis Inhibitors. Figure 5 Nucleotides at the binding sites of chloramphenicol, erythromycin and clindamycin at the peptidyl transferase center. The nucleotides that are within 4.4 A of the antibiotics chloramphenicol, erythromycin and clindamycin in 50S-antibiotic complexes are indicated with the letters C, E, and L, respectively, on the secondary structure of the peptidyl transferase loop region of 23S rRNA (the sequence shown is that of E. coll). The sites of drug resistance in one or more peptidyl transferase antibiotics due to base changes (solid circles) and lack of modification (solid square) are indicated. Nucleotides that display altered chemical reactivity in the presence of one or more peptidyl transferase antibiotics are boxed. 

A famous example of the use of nitro compounds in synthesis was the original synthesis of the antibiotic chloramphenicol (8), which is still used to treat tropical diseases. This synthesis also confirmed the structure of chloramphenicol and established that the (-)-thrco compound was the biologically active stereoisomer. 

What could be the signal for the induction of the cold shock proteins It has been observed that shifting E. coli cells from 37 to 5 °C results in an accumulation of 70S monosomes with a concomitant decrease in the number of polysomes [129]. Further, it has been shown that a cold shock response is induced when ribosomal function is inhibited, e.g. by cold-sensitive ribosomal mutations [121] or by certain antibiotics such as chloramphenicol [94]. These data indicate that the physiological signal for the induction of the cold shock response is inhibition of translation caused by the abrupt shift to lower temperature. Then, the cold shock proteins RbfA, CsdA and IF2 associate with the 70S ribosomes to convert the cold-sensitive nontranslatable ribosomes into cold-resistant translatable ribosomes. This in turn results in an increase in cellular protein synthesis and growth of the cells. 

The antibiotic is administered orally as the palmitate, which is tasteless this is hydrolysed to chloramphenicol in the gastrointestinal tract. The highly water-soluble chloramphenicol sodium succinate is used in the parenteral formulation, and thus acts as a pro-drug. 

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