The fluoroquinolones represent an important therapeutic advance and are extremely
useful agents. They are important for the treatment of Gram-negative urinary tract
infections, especially those from sulfa-resistant strains of E. coli, and for the treatment
of serious bacterial infections such as those caused by Pseudomonas aeruginosa. On the
basis of microbiological considerations, the fluoroquinolones may be further subdivided
into three groups:
- Good Gram-negative activity; poor Gram-positive activity
norfloxacin - Excellent Gram-negative activity; moderate Gram-positive activity
ciprofloxacin, enoxacin, lomefloxacin, levofloxacin, ofloxacin, perfloxacin - Excellent Gram-negative activity; very good Gram-positive activity
clinafloxacin, gatifloxacin, sparfloxacin
These compounds exert their antibacterial effect by inhibiting the bacterial DNA gyrase
(topoisomerase II) enzyme. By inhibiting this enzyme, these drugs prevent the super-
coiled bacterial DNA from undergoing normal transcription and translation. Some
quinolones also inhibit the topoisomerase IV enzyme, thereby interfering with separation
of replicated chromosomal DNA into the respective daughter cells during cell division.
9.5 Drug Design Targeting Fungi
Fungi are non-photosynthetic microorganisms growing as a mass of branching, inter-
lacing filaments (“hyphae”) known as mycelium. The entire organism is a coenocyte
(a multinucleate mass of continuous cytoplasm) confined within a series of branching
tubes. The fungal kingdom includes molds, yeasts, rusts, and mushrooms. Many fungi
cause plant diseases, but only about 100 of the thousands of known yeasts and molds
cause disease in humans. Fungal infections in humans are known as mycoticinfections.
Human mycotic infections may be grouped as superficial (skin [tinea corporis], hair
EXOGENOUS PATHOGENS AND TOXINS 581