Antibiotics cell wall synthesis inhibitors

Category Antibiotic, lipoglycopeptide, Cell wall synthesis inhibitor... 

Beta-Lactam Antibiotics Other Cell Wall Synthesis Inhibitors... 

BETA-LACTAM ANTIBIOTICS OTHER CELL WALL SYNTHESIS INHIBITORS / 375... 

Tsuchiya K, Kobayashi S, Nishikiori T, Nakagawa T, Tatsuta K (1997) Epopromycins, Novel Cell Wall Synthesis Inhibitors of Plant Protoplast Produced by Streptomyces sp. NK04000. J Antibiot 50 261... 

In general, penicillins exert thek biological effect, as do the other -lactams, by inhibiting the synthesis of essential structural components of the bacterial cell wall. These components are absent in mammalian cells so that inhibition of the synthesis of the bacterial cell wall stmcture occurs with Htde or no effect on mammalian cell metaboHsm. Additionally, penicillins tend to be kreversible inhibitors of bacterial cell-wall synthesis and are generally bactericidal at concentrations close to thek bacteriostatic levels. Consequently penicillins have become widely used for the treatment of bacterial infections and are regarded as one of the safest and most efficacious classes of antibiotics. 

Other inhibitors of cell wall synthesis. Bacitracin and vancomycin interfere with the transport of pepti-doglycans through the cytoplasmic membrane and are active only against gram-positive bacteria. Bacitracin is a polypeptide mixture, markedly nephrotoxic and used only topically. Vancomycin is a glycopeptide and the drug of choice for the (oral) treatment of bowel inflammations occurring as a complication of antibiotic therapy (pseudomembranous enterocolitis caused by Clostridium difficile), it is not absorbed. 

Pharmacology This product is a formulation of imipenem, a thienamycin antibiotic, and cilastatin sodium, the inhibitor of the renal dipeptidase, dehydropeptidase-1, which is responsible for the extensive metabolism of imipenem when it is administered alone. Cilastatin prevents the metabolism of imipenem, increasing urinary recovery and decreasing possible renal toxicity. The bactericidal activity of imipenem results from the inhibition of cell-wall synthesis, related to binding to penicillin-binding proteins (PBP). 

It is an antibiotic obtained from S. orchidaceus. It is a chemical analogue of D-alanine. It is a second line tuberculostatic antitubercular drug and inhibitor of cell wall synthesis. 

Examples of enzyme inhibitors that can be used as drugs Enzyme inhibitors can be used as drugs, inhibiting either intracellular or extracellular reactions. For example, the p-lactam antibiotics, such as penicillin and amoxicillin, act by inhibiting one or more of the enzymes of bacterial cell wall synthesis. 

ANTIBIOTICS 0-LACTAMASE INHIBITORS. The antibacterial effectiveness of penicillins, cephalosporins, and other 0-lactam antibiotics depends on selective acylation and consequently, inactivation, of transpeptidases involved in bacterial cell wall synthesis. This acylating ability is a result of the reactivity of the 0-lactam ring (1). Bacteria that are resistant to 0-lactam antibiotics often produce enzymes called 0-lactamases that inactivate the antibiotics by catalyzing the hydrolytic opening of the 0-lactam... 

Inhibitors are substances that tend to decrease the rate of an enzyme-catalysed reaction. Although some act on the substrate, the discussion here will be restricted to those inhibitors which combine directly with the enzyme. Inhibitors have many uses, not only in the determination of the characteristics of enzymes, but also in aiding research into metabolic pathways where an inhibited enzyme will allow metabolites to build up so that they are present in detectable levels. Another important use is in the control of infection where drugs such as sulphanilamides competitively inhibit the synthesis of tetrahydrofolates which are vitamins essential to the growth of some bacteria. Many antibiotics are inhibitors of bacterial protein synthesis (e.g. tetracyclin) and cell-wall synthesis (e.g. penicillin). 

The second stage of cell wall synthesis. An ATP-requiring amidation of glutamic acid that occurs between steps 2 and 3 has been omitted. Points of action of the antibiotic inhibitors bacitracin and vancomycin are indicated. 

Chapter 43. Beta-Lactam Antibiotics Other Inhibitors of Cell Wall Synthesis... 

Katzung PHARMACOLOGY, 9e > Section VIII. Chemotherapeutic Drugs > Chapter 43. Beta-Lactam Antibiotics Other Inhibitors of Cell Wall Synthesis > ... 

Cycloserine is an inhibitor of cell wall synthesis and is discussed in Chapter 43 Beta-Lactam Antibiotics Other Inhibitors of Cell Wall Synthesis. Concentrations of 15-20 jrg/mL inhibit many strains of M tuberculosis. The dosage of cycloserine in tuberculosis is 0.5-1 g/d in two divided doses. Cycloserine is cleared renally, and the dose should be reduced by half if creatinine clearance is less than 50 mL/min. 

Two other irreversible inhibitors are penicillin G (4.18), a /3-lactam antibiotic, and orlistat (Xenical or Alii, 4.19), an antiobesity drug (Figure 4.19). Penicillin G inhibits cell wall synthesis in bacteria, while orlistat inhibits the breakdown of fats in the small intestine.16 Both drugs contain acid derivatives in a strained four-membered ring. Nucleophiles in the active sites of the inhibited enzymes attack the reactive carbonyl groups and open the strained ring in an energetically favorable, irreversible process. 

Summary of antimicrobial agents affecting cell wall synthesis [Note Cilastatin is not an antibiotic but a peptidase inhibitor that protects imipenem from degradation.]... 

Selective inhibition of bacterial cell wall synthesis (penicillins, cephalosporins, bacitracin, vancomycin). Following attachment to receptors (penicillinbinding proteins), p-lactam antibiotics inhibit transpeptidation enzymes and thereby block the final stage of peptidoglycan sysnthesis. This action is followed by inactivation of an inhibitor of autolytic enzymes in the bacterial cell wall. Bacitracin and vancomycin inhibit early stages of peptidoglycan synthesis. 

The inhibitors of bacterial cell-wall synthesis are the beta lactam antibiotics (the penicillins and cephalosporins) (Figure V-l-l), the carbapenems, vancomycin, and aztreonam. 

Bacterial infections are treated with antibiotics. There are many antibiotics available, but they fall into three major groups based on their mode of action inhibitors of bacterial nucleic acid synthesis inhibitors of cell wall synthesis and inhibition of bacterial protein synthesis. Resistance of bacteria to commonly-used antibiotics has become a major problem necessitating the development of new antibiotics. Tuberculosis infection is difficult to treat and requires a combination of at least three different antibiotics. 

Inhibitors of bacterial cell wall synthesis include some of the most widely used antibiotics. Also found in this category are several interesting but lesser known compounds with narrower utility. 

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