Mahmud's Portfolio - Antibacterial agents

Antibacterial agents

Learning objectives: Learn about antibacterial agents, their classification, chemistry, medicinal chemistry and structure activity relationship of antibacterial agents.

Antibacterial agents

Antibacterial Substances or antimicrobial chemotherapeutic agents are chemical substances used in the treatment of infectious diseases caused by pathogenic microorganisms. Their mode of action is to interfere with microbial metabolism; thereby producing a bacteriostatic or bacteriocidal effect on the microorganisms, without producing a like effect on the host cells.

Example:

Bacterial 30 s Ribosomal subunit inhibitors: Tetracyclines

Bacterial 50 s Ribosomal subunit inhibitors: Macrolides, Chloramphenicol, Erythromycins,

Bacterial cell wall inhibitors: Penicillins, Carbapenems, Cephalosporines

Folic Acid synthesis inhibitors: Sulfonilamides

Antibiotics are synthesized and secreted by some true bacteria, actinomycetes (Soil bacteria), and fungi. These molecules are designed in nature to inhibit or prevent the growth of other microorganisms in the environment. Today, antibiotics have been designed or modified based on this basic principle. There are other synthetic drugs produced through drug research that are capable of inhibiting bacterial growth.

Bacteriostatic Antibacterial Agents are the antibiotic agents which only inhibit (or retard) the growth and proliferation of bacteria, but do not kill them, rather the bacteria will destroy by their own toxin or by the completion of their certain life span, are called bacteriostatic Agents.

For example- The sulfonamides are primarily bacteriostatic, which means they slow or retard the multiplication of bacteria. This bacteriostatic activity is due to sulfonamide antagonism to para-aminobenzoic acid (PABA), a substance that some, but not all, bacteria need to multiply. Once the rate of bacterial multiplication is slowed, the defense mechanisms of the host (white blood cells) is able to rid the body of the invading microorganisms and therefore control the infection.

Bacteriocidal Antibacterial Agents are the antibiotic agents which can kill bacteria.

For example- Penicillins, Aminoglycosides.

Pathologic microorganism-Microorganisms in a certain amount that can produce diseases are called pathologic microorganism or pathogenic microorganism.

Anti-organism- Substances that are active against pathogenic microorganism are called anti-organism.

Causative microorganism- A specific microorganism which can causes a specific disease is called causative microorganism for that disease. For example-Salmonela typhi is the causative microorganism for typhoid, Mycobacterium Leprae for leprosy, Mycobacterium tubercoli for tuberculosis.

Predatorship- When one animal destroys another animal is called Predatorship. The tern Predatorship is confined in animal.

Antibiosis- When one living substance destroys another living substance (microorganism) then this is called antibiosis. The term “antibiosis” was first used by Charles Chamberland. This includes both plant and animal.

Antibiotics- Antibiotics are those substances which are derived from nonpathogenic microorganisms (bacteria, fungi, actinomycotes and also some non-pathogenic organism) and are used for either killing or inhibiting the growth of pathogenic microorganism without affecting the host tissues.

Antibiotics are specific chemical substances derived from or produced by living organisms that are capable of inhibiting the life processes of other organisms. The first antibiotics were isolated from microorganisms but some are now obtained from higher plants and animals. Over 3,000 antibiotics have been identified but only a few dozen are used in medicine. Antibiotics are the most widely prescribed class of drugs comprising 12% of the prescriptions in the United States.

For example-

I. Penicillin [Benzyl penicillin (Pen-G)] was first extracted from the mold/fungi Penicillium notatum.

II. Cephaiosporin in obtained from the mold/fungus Cephaiosporium acremonium.

III. Chloramphenicol- a synthetically manufactured broad-spectrum antibiotic initially isolated from the bacteria Streptomyces venezuelae in 1948 and was the first bulk produced synthetic antibiotic.

Antimicrobial drugs are used principally for the prophylaxis and treatment of bacterial infections.

Substitution on the Amino (NH2) group exerts variable effects on microorganisms. Bacteria synthesize benzoic acid (PABA) is a constitution of heterocyclic aromatic ring at 1-nitrogen with P.A.B.A. produce highly potent compound thus bacteria cannot synthesis Folic Acid and cannot multiply. Then they may killed by the action of sulfa drugs by their own metabolic toxicity.

[Remember:-Growth cycl (curve) of Bacteria. PELCZEAR:Microbiology]

Classification of Antimicrobial Agents

Several attempts were taken to classify the antibacterial agents. Among them, some most acceptable classifications are-

A. According to the type of killing to the bacteria, antibiotics can be classified as follows:

I. Bacteriocidal antibiotics: Kill bacteria

II. Bacteristatic antibiotics: Stop multiplication of bacteria: Macrolides are bacteriostatic for most bacteria.

B. According to the spectrum of activity:

I. Short spectrum or narrow-spectrum antibiotic: These target a specific type of bacterial infection and active against either gram positive cocci and bacilli or gram negative bacteria. For example- penicillin G, Streptomycin, Erythromycin, Cloxacillin.

II. Broad spectrum or wide-spectrum antibiotic: These are effective against a wide range of bacteria, fungi, protozoa, yeast etc. A broad-spectrum antibiotic acts against both Gram-positive and Gram-negative bacteria, in contrast to a narrow-spectrum antibiotic, which is effective against specific families of bacteria. For example- Ciprofloxacin, Amoxycillin, Ampicillin, Cephalosporin.

III. True broad spectrum antibiotic:: For example- Tetracycline.

C. According to the type of mechanism of action, antibacterial agents are classified as:

I. Inhibitors of cell wall synthesis:

Cell wall synthesis inhibitors generally inhibit some step in the synthesis of bacterial peptidoglycan-a protein that made up the bacterial cell wall. Inhibition of cell wall synthesis leads to bacterial cell wall lysis (brusting) and death. Generally they exert their selective toxicity against eubacteria because human cells lack cell walls. As animal cells do not have a cell wall, they remain unaffected by such agents. Agents operating in this way include Penicillin, Cephalosporins, Cycloserine, Bactracin.

II. Interferer or Inhibitor of intermediary cell metabolism:

Antibacterial agents which inhibit cell metabolism of bacteria are called antimetabolites. These compounds inhibit the metabolism of a microorganism, but not the metabolism of the host. They do this by inhibiting an enzyme-catalyzed reaction which is present in the bacterial cell but not in animal cells. They inhibit synthesis of purine and thymidylate precursors folic acid or tetrahydrofolate. The best known examples of antibacterial agents acting in this way are the Sulphonamides, PAS, Trimethoprim, etc.

III. Drugs that interact with the permiability of plasma membrane:

Some antibacterial agents bind and interact with the plasma membrane of the bacterial cells to affect membrane permeability (making it more permeable), cause leakage of cell membrane, this interferes the transport through membrane. The resulting water uptake leads to cell death. Polymixin, Tyrothricin, Colistin, Polyenes- Amphotercin-B, Nystatin operate in this way. These antibiotics are cationic, basic proteins that act like detergents (surfactants) and so often called detergent like antibiotics. They are bactericidal for gram-negative bacteria and have little to no effect on gram-positive since cell wall is too thick to permit access to membrane.

iv. Inhibitors or disruptors of protein synthesis:

Disruption of protein synthesis means that essential enzymes required for the survival of the cell can no longer be made. Agents which disrupt protein synthesis include the Aminoglycosides such as Erythromycin; tetracyclines, and chloramphenicol. etc.

V. Disrupters of nucleic acid synthesis or Inhibitors of nucleic acid transcription and replication:

Inhibition of nucleic acid function prevents cell division and/or, the synthesis of essen¬tial enzymes. The enzyme RNA polymerase synthesizes RNA according to a DNA template. The antibiotic rifampin interferes with prokaryotic RNA polymerase and thus, interferes with transcription. Fluoroquinolones inhibit DNA gyrase, a bacterial enzyme that unwinds DNA in preparation for replication and transcription. Both of these disruptions prevent bacteria from dividing to make more bacteria. Agents acting in this way include nalidixic acid and profalvin.

V. Interferers with DNA synthesis: Example- Zodovudine, Idoxuridine.

VI. Interferers with DNA function: For example- Refampicin (Rifampin), Norfloxacin, Metronidazole.

VII. Cause misreading of m-RNA: For example- Aminoglycosides- Streptomycin, Neomycin etc.