Antimicrobial Chemotherapeutic Agents

Antimicrobial Chemotherapeutic Agents

• Chemotherapy began with Paul Ehrlich in the early 1900s.
• Ehrlich received the Nobel Prize for Medicine in 1908.
• In 1906, he discovered the chemical compound atoxyl, effective against sleeping sickness (trypanosomiasis).
• In 1909, Ehrlich and Sahachiro Hata developed Salvarsan (arsphenamine), a treatment for syphilis.
• Gerhard Domagk, a German pathologist and bacteriologist, discovered the first commercially available antibiotic, Prontosil, in 1939.
• He received the Nobel Prize in Medicine in 1939.
• Prontosil decomposes into a highly active sulphonamide and a toxic compound thiaminobenzene in the body.
• The "golden age" of antimicrobial therapy began with penicillin discovery in 1929.
• Sir Alexander Fleming noticed that the growth of staphylococci was inhibited around a Penicilian notatum mold accidentally growing on a culture plate.
• Penicillin was extracted and mass-produced in 1940 by Florey and Chain.
• Howard Florey and Ernest Chain shared the 1945 Nobel Prize in Physiology or Medicine with Fleming for the discovery of penicillin.

Definitions

• Antibiotics: A natural substance produced by a microorganism to kill another.
• Anti-infectives/Anti-microbials: Any agent (natural or synthetic) that kills pathogens (microbes).

Classification of Antibiotics

• Origin: Microorganisms (bacteria, fungi, actinomycetes), synthetic, semi-synthetic antibiotics.
• Chemical Structure: Beta-lactam antibiotics, aminoglycosides, aminocyclitols, chloramphenicol, tetracyclines, polyenes, macrolides.
• Spectrum of Biological Action: Antibacterial, antifungal, antitumor, antiprotozoal, antiviral.
• Mode of Action: Inhibitors of cell wall synthesis, antibiotics acting on cell membranes, inhibitors of protein synthesis, inhibitors of nucleic acid synthesis, inhibitors of folic acid synthesis (antifolates).

Examples of Microbial Sources of Antibiotics

• Gram-Positive Rods: Bacitracin (Bacillus subtilis), Polymyxin (Bacillus polymyxa)
• Actinomycetes: Amphotericin B (Streptomyces nodosus), Chloramphenicol, Chlortetracycline and tetracycline, Erythromycin, Neomycin, Streptomycin, Gentamicin (Streptomyces spp)
• Fungi: Cephalothin, Griseofulvin (Penicillium spp), Penicillin (Penicillium notatum).

Specific Classes of Antibiotics

• Beta-lactam Antibiotics: Broad class containing penicillins, cephalosporins, and cephmycins. Have a β-lactam nucleus in their structure. Includes detailed images of structures.
• Aminoglycosides: Glycosidic derivatives of streptamine, including streptomycin, dihydrostreptomycin, neomycin, kanamycin, tobramycin, amikacin, and gentamicin; derived from Streptomyces (suffix -mycin) or Micromonospora (suffix -micin). Includes detailed structures.
• Aminocyclitols: Closely related to aminoglycosides, but lack amino sugar components. Includes spectinomycin as an example and includes a detailed structure.
• Tetracyclines: Family of four-ringed antibiotics: tetracycline, chlorotetracycline, oxytetracycline, demeclocycline, doxycycline, and minocycline
• Polyenes: Large ring containing a lactone group and a hydrophobic region with conjugated double bonds, including nystatin, amphotericin B. Features detailed structures.
• Macrolides: Consist of a macrocyclic lactone ring with attached sugars; examples include erythromycin, oleandomycin, and spiramycin. Includes structures.

Spectrum of Biological Action

• Antibacterial Antibiotics: Narrow spectrum (e.g., natural penicillins, erythromycin, polymyxin); broad spectrum (e.g., tetracyclines, chloramphenicol); tuberculostatic (e.g., streptomycin, kanamycin, cycloserine).
• Antifungal Antibiotics: Nystatin, amphotericin B, griseofulvin, and candicin.
• Antitumor Antibiotics: Actinomycins, mitomycins.
• Antiprotozoal Antibiotics: Fumagillin.
• Antiviral Antibiotics: Helinine.

Mode of Action (Example: Cell Wall Inhibitors)

• Inhibitors of cell wall synthesis: Block the synthesis of peptidoglycan (components: N-acetylmuramic acid, N-acetylglucosamine, and oligopeptides). Examples include penicillins, cephalosporins, bacitracin, vancomycin, teicoplanin, and cycloserine.
• Includes details about the enzymes involved in peptidoglycan synthesis: Racemases, Synthetase, Transpeptidases .

Explore the history and development of antimicrobial chemotherapeutic agents, including the pioneers like Paul Ehrlich and Alexander Fleming. This quiz covers key discoveries from atoxyl to penicillin, highlighting the evolution of treatments for infectious diseases. Test your knowledge on the milestones that shaped modern medicine.