DNA topoisomerases as targets for chemotherapy

DNA topoisomerases are ubiquitous enzymes that alter the configuration or topology of DNA. These enzymes play an important role in replicational, recombinational, and transcriptional events and are a key to cell growth processes. A number of therapeutically useful drugs apparently exert their effects by interfering with DNA topoisomerization reactions. Several inhibitors of bacterial DNA topoisomerase II (DNA gyrase) have been developed. Most of these possess a 4-quinolone nucleus and are highly bactericidal for a variety of microorganisms; at therapeutically effective levels, these compounds do not inhibit the human topoisomerases. Other drugs, structurally distinct from the DNA gyrase inhibitors, inhibit the human type II DNA topoisomerase. These drugs, including m-AMSA and VP16-23, are proving useful in the treatment of several neoplasms.