DNA topoisomerases are the targets of important anticancer and antibacterial drugs. Camptothecins and novel noncamptothecins in clinical development (indenoisoquinolines and ARC-111) target eukaryotic type IB topoisomerases (Top1), whereas human type IIA topoisomerases (Top2alpha and Top2beta) are the targets of the widely used anticancer agents etoposide, anthracyclines (doxorubicin, daunorubicin), and mitoxantrone. Bacterial type II topoisomerases (gyrase and Topo IV) are the targets of quinolones and aminocoumarin antibiotics. This review focuses on the molecular and biochemical characteristics of topoisomerases and their inhibitors. We also discuss the common mechanism of action of topoisomerase poisons by interfacial inhibition and trapping of topoisomerase cleavage complexes.

HIV integrase is a rational target for treating HIV infection and preventing AIDS. It took approximately 12 years to develop clinically usable inhibitors of integrase, and Phase I clinical trials of integrase inhibitors have just begun. This review focuses on the molecular basis and rationale for developing integrase inhibitors. The main classes of lead compounds are also described, as well as the concept of interfacial inhibitors of protein-nucleic-acid interactions that might apply to the clinically used strand-transfer inhibitors.