Antibiotics - penicillins

Several drugs in current medical use are mechanism-based enzyme inactivators. Eor example, the antibiotic penicillin exerts its effects by covalently reacting with an essential serine residue in the active site of glycoprotein peptidase, an enzyme that acts to cross-link the peptidoglycan chains during synthesis of bacterial cell walls (Eigure 14.17). Once cell wall synthesis is blocked, the bacterial cells are very susceptible to rupture by osmotic lysis, and bacterial growth is halted. 

The commercial production of penicillin and other antibiotics are the most dramatic in industrial microbiology. The annual production of bulk penicillin is about 33 thousand metric tonnes with annual sales market of more than US 400 million.8 The worldwide bulk sales of the four most important groups of antibiotics, penicillins, cephalosporins, tetracyclines and erythromycin, are US 4.2 billion per annum.10... 

Excretion via the kidney can be a straightforward question of glomerular filtration, followed by passage down the kidney tubules into the bladder. However, there can also be excretion and reabsorption across the tubular wall. This may happen if an ionized form within the tubule is converted into its nonpolar nonionized form because of a change in pH. The nonionized form can then diffuse across the tubular wall into plasma. Additionally, there are active transport systems for the excretion of lipophilic acids and bases across the wall of the proximal tubule. The antibiotic penicillin can be excreted in this way. 

Lactam antibiotics—penicillins, cephalosporins, carbapenems and 4.3 Nitroimidazoles (metronidazole) and nitrofurans (nitrofurantoin)... 

Enzymatic trapping Some -lactam antibiotics Penicillin-binding proteins... 

Type I IgE Anaphylaxis, urticaria P-Lactam antibiotics penicillins (primarily), cephalosporins, carbapenems Non-fl-lactam antibiotics sulfonamides, vancomycin Others insulin, heparin... 

Oxygen activation is a central theme in biochemistry and is performed by a wide range of different iron and copper enzymes. In addition to our studies of the dinuclear non-heme iron enzymes MMO and RNR, we also studied oxygen activation in the mononuclear non-heme iron enzyme isopenicillin N synthase (IPNS). This enzyme uses O2 to transform its substrate ACV to the penicillin precursor isopenicillin N [53], a key step in the synthesis of the important P-lactam antibiotics penicillins and cephalosporins [54, 55],... 

Vaccine is available for cutaneous, possibly inhalation, anthrax. Cutaneous anthrax responds to antibiotics (penicillin, terramydn, Chloromycetin), sulfadiazine, and immune serum. Pulmonary (inhaled) anthrax responds to immune serum in initial stages but is of little use after disease is well established. Intestinal, same as for pulmonary. 

Fig. 6. A Chromatogram of a mixture containing the print molecule (oxacillin), two other p-lactam-antibiotics (penicillin G and penicillin V) and a non- 3-lactam-antibiotic (bacitracin) on an oxacillin imprinted MIP containing 4-vinylpyridine residues, cross-linked with TRIM. The analysis was performed in organic mobile phase (ACN/AcOH,99 l).B Same conditions but using the respective non-imprinted control polymer. C Structures of penicillin V, penicillin G, and oxacillin. Reprinted with permission from Skudar K, Briiggemann O, Wittelsberger A, Ramstrom O (1999) Anal Commun 36 327. Copyright 1999 The Royal Society of Chemistry...

Antibiotics P-Lactam antibiotics (penicillin, Johns Hopkins/Columbia Univ., Palm... 

To be an effective antibacterial agent, a drng mnst inhibit an enzyme that is present in the bacteria bnt not in the host. One well-known example is a transpeptidase involved in cell wall synthesis in some bacteria. Inhibition prevents bacteria from synthesising their cell wall so that proliferation stops. A drng that inhibits this enzyme is the antibiotic, penicillin first nsed in 1941 (see Chapter 17). However, the first dnrg to inhibit bacterial growth was developed from a dye (Box 3.8). 

At the beginning of the twentieth century, arsenic compounds were used to kill spirochete bacteria, which cause the sexually transmitted disease syphilis. After this amphetamine compound was used to treat syphilis in Europe, the disease rate was reduced by more than half. The antibiotic penicillin has replaced arsenic for most medical purposes... 

NRDC estimated that between 100 and 300 deaths each year (depending on which of the provided estimates were used) may be attributable to the subtherapeutic use of penicillin and the tetracyclines in animal feeds. In addition, some 270,000 non-fatal cases of salmonellosis may also be due to the subtherapeutic use of antibiotics (penicillin and the tetracyclines) in animal feeds. 

Although streptomycin was not the first antibiotic (penicillin, a fungal product, had been isolated some years earlier), its discovery was a landmark in antibiotic history. It was the first effective therapeutic for tuberculosis, a disease that had terrorized humans for cenmries and a cause of human morbidity and mortality unmatched by wars or any other pestilence. Streptomycin was the first aminoglycoside to be identified and characterized and is noteworthy in being the first useful antibiotic isolated from a bacterial source. At the present time, the use... 

The rapid and impressive development of organic chemistry in the 19 th century had a tremendous effect on the discoveries of natural products. Towards the end of the 19th century, microbiology has developed enormously. The antibiotic penicillin was first isolated by Alexander Fleming... 

The first natural product antibiotic penicillin, is of a fl-lactam type (Fig. 3). It revolutionized the treatment of infections ever since its introduction for clinical use. Since then, other (l-lactam containing natural product antibiotics and their derivatives, such as cephalosporins, carbapenems. 

Dicloxacillin (Dynapeii/ Dycill) [Antibiotic/Penicillin] Uses ... 

Antibiotics Penicillin Bacitracin Penicillium chrysogenum Bacillus licheniformis... 

Historically, plant-based natural products have been a source of useful drugs. The analgesic opiates come from the poppy plant. Digitalis for congestive heart failure was first isolated from the foxglove plant. Various antibiotics (penicillin) and anticancer agents (taxol) are derived from natural product sources. There are numerous other examples. 

AccessMedicine Print Chapter 43. Beta-Lactam Other Cell Wall- Membrane-Active Antibiotics Penicillin G benzathine (Permapen, Bicillin)... 

Discoveries such as the charting of new planets, land masses, or forms of life are not classified as innovations as they had existed before being observed by humans. When new species are introduced into a society and find a specific use, it can be classified as innovation. A pharmaceutical example of this is the antibiotic penicillin. Although it had existed as a fungal secretion, it was only within the past century that it was used to actively eliminate infectious bacteria. In initial analysis, however, it was not thought to survive long enough within the human body to be effective. 

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