Drug Names and Classifications

Drug Names

• Code number – assigned to new compounds before testing
• Chemical name – name as prescribed by the IUPAC nomenclature system
• Generic/non-proprietary name – shortened version/acronym of the chemical name, typically used in scientific literature and by pharmacists/doctors
• Trade name – patented name for a specific drug formulation; often indicates the targeted disease, and a drug with a single generic name can have multiple trade names (due to different formulations or manufacturers after patent expiry).

Example of Drug Names

• HIV Protease inhibitor – Saquinavir mesylate
• Code number – Ro 318959
• Generic name – saquinavir
• Chemical name – (S)-N-((aS)-A-((1R)-2-(3S, 4a S, 8aS)-3-tbutylcarbamoyl)octahydro-2-(1H)isoquinolinyl)-1-hydroxyethyl)phenethyl-2-quinaldamido)-succinamide mesylate
• Trade name – Invirase

Anti-bacterial Agents

• Bacteria – single-celled organisms without nuclei, possessing a phospholipid membrane and DNA dispersed around the cytoplasm
• Antibiotic – antibacterial agent derived from a natural source (e.g., from kin bactena)
• Bacteria are divided into two types based on the Gram test

Gram Test

• Developed by Hans Christian Gram (1853–1938)
• A heteroaromatic purple stain (crystal violet) mixed with bacteria, adheres to the outer membrane
• After decolorization with an organic solvent, Gram-negative bacteria appear red, while Gram-positive bacteria appear purple

Important Species of Bacteria

Mode of Action of Sulfonamides

• Prontosil, initially developed by Bayer, is an azodye converted into sulfanilamide within the body.
• Prontosil is a prodrug, metabolized into the biologically active form of sulfanilamide.

Activation of Prontosil

• Prontosil is originally biologically inactive, but via enzymatic reduction (H″ reduction in vivo) is changed into the active sulfanilamide, the first sulfa drug.

Structure-Activity Relationships (SAR)

• Method for optimizing drug activity
  • Para-amino group essential, must be a primary amine
  • Aromatic ring and sulfonamide are essential
  • Sulfonamide can be primary or secondary
  • R' is the only modifiable position

Improved Sulfa Drugs

• Sulfanilamide is poorly water-soluble and toxic
• Second-generation drugs, such as sulfadiazine, are more water-soluble due to polarity changes

Site of Action of Sulfa Drugs

• Discovered by D. Wood in Oxford (1940)
• Dihydropteroate synthetase enzyme involved in folic acid biosynthesis
• Folic acid essential for transporting 1-carbon units in various oxidation states, and is necessary for the biosynthesis of DNA
• Mammals cannot produce folic acid, but need it from their diet.

Biosynthesis of Folic Acid

• Diagram illustrating the biochemical pathway for folic acid production
• (Diagram shows substrates and enzymes involved in the folic acid biosynthesis pathway.)

Sulfa Drugs as Competitive Inhibitors

• Sulfanilamide competes with PABA for the active site of dihydropteroate synthetase, functioning as a reversible competitive inhibitor.
• A good inhibitor ideally has a low dissociation constant Ki relative to the Km value for the substrate to ensure high substrate affinity

Antibacterial Agents Targeting DHFR

• Bacterial DHFR is structurally different from human DHFR (useful target for anti-cancer agents)
• Trimethoprin a competitive DHFR inhibitor, employed as an antibacterial and anti-malarial agent

Septrin: A Synergistic Mixture

• Trimethoprin and sulfamethoxazole are often administered in combination (Septrin) to counter resistance to one drug
• Anti-metabolites block enzymes in metabolic pathways; bacteriostatic drugs inhibit growth and replication (without direct killing)