A series of amide-coupled bisanthrapyrazole derivatives of 7-chloro-2-[2-[(2-hydroxyethyl)methylamino]ethyl]anthra[1,9-cd]pyrazol-6(2H)-one (AP9) were designed using molecular modeling and docking and synthesized in order to develop an anticancer drug that formed a strongly binding bisintercalation complex with DNA. Concentration dependency for the increase in the DNA melting temperature was used to determine the DNA binding strength and whether bisintercalation occurred for the newly synthesized analogs. The ability of the compounds to inhibit the growth of the human erythroleukemic K562 cell line and inhibit the decatenation activity of DNA topoisomerase IIalpha was also measured. Finally, the compounds were evaluated for their ability to act as topoisomerase II poisons by measuring the topoisomerase IIalpha-mediated double strand cleavage of DNA. All of the bisanthrapyrazoles inhibited K562 cell growth and topoisomerase IIalpha in the low micromolar range. Compounds with either two or three methylene linkers formed bisintercalation complexes with DNA and bound as strongly as, or more strongly than, doxorubicin. In conclusion, a novel group of amide-coupled bisintercalating anthrapyrazole compounds were designed, synthesized, and evaluated for their physico-chemical and biologic properties as potential anticancer agents.