Antibiotics represent one of the greatest achievements in modern medicine, transforming once-lethal infections into manageable conditions. Their discovery reshaped public health, surgery, and clinical practice across the globe. Unit 1 focuses on the historical evolution of antibiotics, their chemical foundations, and the structure–activity relationships that determine their effectiveness. This article explores major antibiotic classes, including β-lactams, aminoglycosides, and tetracyclines, highlighting their chemistry, degradation, and important representatives.
Download UNIT 1 – Antibiotics Notes
Get simplified revision notes for this unit:
⬇️
Download Unit 1 Notes PDF
Historical Background of Antibiotics
The antibiotic era began in the early 20th century with the accidental discovery of penicillin by Alexander Fleming in 1928. This breakthrough revealed that microorganisms could produce substances capable of inhibiting or killing other microbes. Subsequent decades witnessed the discovery of streptomycin, tetracyclines, and cephalosporins, ushering in a golden age of antimicrobial therapy. These developments drastically reduced mortality from bacterial infections and laid the foundation for modern chemotherapy against infectious diseases.
Nomenclature and Classification of Antibiotics
Antibiotics are named based on their chemical structure, biological source, or spectrum of activity. For example, penicillins derive their name from Penicillium species, while aminoglycosides reflect their amino sugar components linked by glycosidic bonds. Classification may be chemical, pharmacological, or microbiological, helping clinicians select appropriate therapy and researchers design improved analogues.
Stereochemistry and Its Role in Antibiotic Activity
Stereochemistry plays a critical role in antibiotic effectiveness. Many antibiotics contain chiral centers, and only specific stereoisomers exhibit optimal antibacterial activity. Alterations in spatial arrangement can reduce binding affinity to bacterial targets, decrease potency, or increase toxicity. Understanding stereochemical orientation is essential in antibiotic synthesis and optimization.
Structure–Activity Relationship (SAR) in Antibiotics
Structure–activity relationship studies explain how chemical modifications influence antimicrobial activity. Minor changes in functional groups can alter bacterial penetration, resistance to enzymatic degradation, or affinity for microbial enzymes and ribosomes. SAR knowledge has guided the development of semisynthetic antibiotics with enhanced spectrum, stability, and reduced resistance.
β-Lactam Antibiotics: The Backbone of Antibacterial Therapy
General Characteristics
β-Lactam antibiotics are defined by the presence of a β-lactam ring, which interferes with bacterial cell wall synthesis. This action leads to osmotic instability and bacterial cell death.
Penicillins
Penicillins consist of a β-lactam ring fused to a thiazolidine ring. Their activity depends on side-chain substitutions that influence spectrum and acid stability. However, penicillins are susceptible to hydrolytic degradation by β-lactamases, leading to resistance.
Cephalosporins
Cephalosporins contain a β-lactam ring fused to a dihydrothiazine ring, offering greater resistance to enzymatic degradation. Chemical modifications across generations have expanded their antibacterial spectrum and improved pharmacokinetic properties.
β-Lactamase Inhibitors
These agents, such as clavulanic acid, possess minimal antibacterial activity but protect β-lactam antibiotics from enzymatic breakdown. When combined with penicillins, they restore efficacy against resistant strains.
Monobactams
Monobactams contain a monocyclic β-lactam structure and show selective activity against gram-negative bacteria. Their structural simplicity reduces cross-reactivity in penicillin-allergic patients.
Aminoglycosides: Potent Bactericidal Agents
Chemical Nature and Mechanism
Aminoglycosides consist of amino sugars linked to a central aminocyclitol ring. They exert bactericidal action by binding irreversibly to bacterial ribosomes, causing misreading of genetic code and inhibition of protein synthesis.
Streptomycin
Streptomycin was the first effective drug against tuberculosis. Chemically, it is highly polar and unstable in acidic conditions, limiting oral administration.
Neomycin
Neomycin exhibits strong activity against gram-negative bacteria but is primarily used topically due to nephrotoxicity concerns.
Kanamycin
Kanamycin is chemically stable and effective against resistant organisms. Structural modifications have led to semisynthetic derivatives with improved safety profiles.
Chemical Degradation
Aminoglycosides undergo degradation through hydrolysis and oxidation, especially under alkaline conditions, reducing antimicrobial potency.
Tetracyclines: Broad-Spectrum Antibiotics with Unique Chemistry
Core Chemical Structure
Tetracyclines possess a four-ring fused system with multiple hydroxyl and keto groups. Their activity depends on maintaining this conjugated structure.
Mechanism of Action
These antibiotics inhibit bacterial protein synthesis by binding reversibly to the 30S ribosomal subunit. They are bacteriostatic rather than bactericidal.
Important Members
Tetracycline: The parent compound, effective against a wide range of bacteria
Oxytetracycline and Chlortetracycline: Naturally occurring derivatives with improved potency
Doxycycline and Minocycline: Semisynthetic analogues with enhanced lipophilicity, better absorption, and longer half-life
Chemical Degradation
Tetracyclines are prone to degradation via epimerization, dehydration, and oxidation, especially under acidic or alkaline conditions. Degraded products may lose activity or cause toxicity, making proper storage essential.