Topoisomerase IIα (Top II) is a critical enzyme that resolves DNA topology during transcription and replication. Inhibitors of Top II are used as anticancer agents and are classified as interfacial poisons (IFPs) or catalytic inhibitors (CICs). Here, we report a novel class of cytotoxic, stable cationic gold(III) Schiff base chelates (AuL1, AuL2, and AuL3) with DNA-intercalating properties. In the NCI-60 screen, AuL1 and AuL3 exhibited potent cytotoxicity (mean GI