Chloramphenicol chemical structure

Antibiotics may be classified by chemical structure. Erythromycin, chloramphenicol, ampicillin, cefpodoxime proxetil, and doxycycline hydrochloride are antibiotics whose primary structures differ from each other (Fig. 19). Figure 20 shows potential oscillation across the octanol membrane in the presence of erythromycin at various concentrations [23]. Due to the low solubility of antibiotics in water, 1% ethanol was added to phase wl in all cases. Antibiotics were noted to shift iiB,sDS lo more positive values. Other potentials were virtually unaffected by the antibiotics. On oscillatory and induction periods, there were antibiotic effects but reproducibility was poor. Detailed study was then made of iiB,sDS- Figure 21 (a)-(d) shows potential oscillation in the presence of chloramphenicol, ampicillin, cefpodoxime proxetil, and doxycycline hydrochloride [21,23]. Fb.sds differed according to the antibiotic in phase wl and shifted to more positive values with concentration. No clear relationship between activity and oscillation mode due to complexity of the antibacterium mechanism could be discovered but at least it was shown possible to recognize or determine antibiotics based on potential oscillation measurement. 

FIG. 19 Chemical structures of (a) erythromycin, (b) chloramphenicol, (c) ampicillin, (d) cefpo-doxime proxetil, and (e) doxycycline hydrochloride. 

Fig. 1 Chemical structures of some of the most important antibiotics used nowadays divided into the most representative families fluoroquinolones, sulfonamides, penicillins, macrolides, and tetracyclines. Another important antibiotic, chloramphenicol, is also shown...

Figure 1.17. Chemical structure of chloramphenicol, the first broad-spectrum antibiotic to gain clinical...

Chloramphenicol, thiamphenicol, and florfenicol are broad-spectrum antibacterials with closely related chemical structures (Fig. 3.2). In thiamphenicol, the p-nitro group on the benzene ring of chloramphenicol is replaced with a methyl sulfonyl group. In florfenicol, the hydroxyl group on the side chain of thiamphenicol is replaced with a fluorine. They are all potent antibacterial agents acting... 

In 1947 a strain of S. venezuelae [1-4] was isolated from a soil sample collected in Venezuela. It produced a wide-spectrum antibiotic called chloramphenicol (1) according to its chemical structure. Due to its simple chemical structure it is still used. It is the only antibiotic produced by the chemical synthesis rather than biosynthetically. Nevertheless, S. venezuelae is used as a model organism in biosynthetic and genetic experiments. 

FIGURE 16.3 Chemical structures of chloramphenicol and thiamphenicol. Thiamphenicol, in which the nitroso group of chloramphenicol is replaced by a methylsulfone group, retains antibiotic activity, but does not cause the aplastic anemia that is a major concern with chloramphenicol therapy. 

Polymorphism refers to the arrangement of a drug in various crystal forms (polymorphs). Polymorphs have the same chemical structure but different physical properties, such as solubility, density, hardness, and compression characteristics. Some polymorphic crystals may have much lower aqueous solubility than the amorphous forms, causing a product to be incompletely absorbed. Chloramphenicol, for example, has several crystal forms, and when given orally as a suspension, the drug concentration in the body depended on the percentage of p-polymorph in the suspension. The p-form is more soluble and better absorbed (Fig. 7). In general, the crystal form that has the lowest... 

Almost contemporaneous with these discoveries, scientists at Parke Davis in Detroit were also studying soil samples from all over the world. These were evaluated at Yale University, and in 1947 they isolated a novel structure from a soil sample taken from near Cararcas in Venezuela. This was, unsurprisingly, christened Streptomyces venezuelae, and the antibiotic was given the name chloramphenicol. Its relatively simple chemical structure was elucidated in 1947, and it was also first used in that year to treat 22 seriously ill... 

Improved stability of the therapeutic agents Encapsulation of the therapeutic agents in the microemulsion structures can offer improvement in the chemical, photochemical and enzymatic stability of the therapeutic agents such as chloramphenicol (chemical stability) [5], arbutin (photostability) [6] and peptides (enzymatic stability)... 

Chloramphenicol was originally produced by fermentation of Streptomyces venezuelae, but its comparatively simple chemical structure soon resulted in several efficient total chemical syntheses. With two asymmetric centers, it is one of four diastereomers, only one of which (1 R,2R) is significantly active. Because total synthesis produces a mixture of all four, the unwanted isomers must be removed before use. Chloramphenicol is a neutral substance that is only moderately soluble in water, because both nitrogen atoms are nonbasic under physiologic conditions (one is an amide and the other a nitro moiety). It was the first broad-spectrum oral antibiotic used in the United States (1947) and was once very popular. Severe potential blood dyscrasia has greatly decreased its use in North America. Although its cheapness and efficiency makes it still very popular in much of the rest of the world where it can often be purchased over-the-counter without a prescription. 

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. 

Phosphorylation is a common mechanism resulting in resistance to the aminoglycoside antibiotics. This chemical strategy also has been associated with resistance to the macrolides such as erythromycin, the tuberactinomycins such as viomycin, and chloramphenicol. The aminoglycoside kinases share 3D structural similarity with the Ser/Thr/Tyr protein kinase family (36), and the conservation of kinase signature sequences in macrolide... 

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