Stanislav Radl* and Scott Daxt Pages 262 - 270 ( 9 )
The development of the quinolone antibacterials has clearly demonstrated that inhibition of topoisomerase activity can constitute an effective means by which to induce selective pathogen cell death. These agents disrupt normal bacterial gyrase protein-DNA substrate interactions and lead to the formation of a ternary "cleavable complex" which results in a bactericidp.l therapeutic mode of action. However, certain structural 'subsets' of quinolones have been shown to be toxic to mammalian cells as a result of competing inhibition of mammalian topoisomerase II activity. The investigation of these congeners has revealed that rather simple molecular modifications to the basic quinolone pharmacophore can potentiate activity against mammalian proteins. Structure-activity relationships have been elucidated in an attempt to selectively target the action of mammalian topoisomerase as a means for anticancer chemotherapy.