Jawaharlal Nehru Technological University Hyderabad B. Pharmacy III Year Medicinal Chemistry-III Previous Question Paper (February/March-2022 - R17)

Penicillins are classified into four main groups: Natural penicillins (e.g., Penicillin G, Penicillin V), Aminopenicillins (e.g., Ampicillin, Amoxicillin), Penicillinase-resistant penicillins (e.g., Methicillin, Cloxacillin), and Extended-spectrum penicillins (e.g., Piperacillin, Ticarcillin).

The mechanism of action involves the inhibition of bacterial cell wall synthesis. Penicillins bind to Penicillin-Binding Proteins (PBPs), which are transpeptidase enzymes responsible for cross-linking peptidoglycan chains. This inhibition prevents the formation of the rigid cell wall, leading to osmotic lysis and cell death.

The degradation occurs primarily through three pathways: 1) Acid-catalyzed hydrolysis: The highly strained beta-lactam ring is susceptible to cleavage by gastric acid, forming penillic acid. 2) Enzymatic degradation: Bacterial beta-lactamase enzymes hydrolyze the amide bond of the beta-lactam ring, rendering the drug inactive. 3) Nucleophilic attack: Amines or alcohols can attack the carbonyl carbon of the beta-lactam ring, leading to ring opening and loss of antibacterial activity.

Tetracyclines are derived from the biological source Streptomyces species, specifically Streptomyces aureofaciens (for chlortetracycline) and Streptomyces rimosus (for oxytetracycline).

The structure of tetracyclines consists of a hydronaphthacene nucleus, which is a system of four linearly fused six-membered rings. Variations in substituents at positions 5, 6, and 7 distinguish individual members such as tetracycline, doxycycline, and minocycline.

The toxicity profile includes: 1) Gastrointestinal disturbances: Nausea, vomiting, and diarrhea. 2) Photosensitivity: Increased susceptibility to sunburn. 3) Dental staining and bone hypoplasia: Tetracyclines chelate calcium, causing permanent yellow-brown discoloration of teeth and inhibition of bone growth in children. 4) Hepatotoxicity and Nephrotoxicity: Often associated with high doses or the use of expired, degraded tetracyclines (Fanconi-like syndrome).