Aspects of Quinolone-DNA Interactions

It has been well documented that the common target of quinolone antibacterials is the bacteria-specific type II DNA topoisomerase, i.e. DNA gyrase (for reviews, see Cozzarelli 1980; Geliert 1981; Wang 1985; Drlica and Franco 1988). These drugs share a common mode of action with anti-cancer drugs by forming a ternary complex with the enzyme and the DNA substrate (Geliert et al. 1977; Sugino et al. 1977; Chen and Liu 1986; Glisson and Ross 1987). The biological consequence of the formation of such a “cleavable complex” is at least two-fold: i) the enzyme is inactivated, leading to the arrest of DNA synthesis in bacterial cells ii) the cleavable complex formation causes unrepairable DNA damage which is believed to trigger recA-dependent SOS repair response and alternatively leading to cell death, presumably by the expression of certain lethal proteins in the cell (Drlica 1984).