Fluoroquinolones, Metronidazole & DHFR Inhibitors

Introduction & unifying theme

• Three drug families that converge on bacterial nucleic-acid metabolism at distinct nodes: sulfonamides / DHFR inhibitors starve the cell of the one-carbon cofactor tetrahydrofolate; fluoroquinolones poison the topoisomerases that manage DNA supercoiling; nitroimidazoles (metronidazole) generate reactive intermediates that fragment DNA.
• All exploit selective toxicity — the human cell either lacks the target (no DNA gyrase; uses preformed dietary folate) or expresses a target with ~10³–10⁵-fold lower drug affinity (human DHFR; mammalian topoisomerase II).
• Folate antagonists and fluoroquinolones are wholly synthetic chemotherapeutic agents (not antibiotics of microbial origin).
• Historically, sulfonamides (Prontosil, 1932–35) were the first systemically effective antibacterials — Domagk won the 1938 Nobel Prize.