A variety of antitumor agents currently used in chemotherapy or evaluated in clinical trials are known to inhibit DNA topoisomerase I or II. We have developed sixteen quantitative structure-activity relationships (QSAR) for different sets of compounds that are camptothecin analogs, 1,4-naphthoquinones, unsaturated acids, benzimidazoles, quinolones, and miscellaneous fused heterocycles to understand chemical-biological interactions governing their inhibitory activities toward topoisomerase I and II.