A Dual Topoisomerase Inhibitor of Intense Pro‐Apoptotic and Antileukemic Nature for Cancer Treatment

Abstract Classic cytotoxic drugs remain indispensable instruments in antitumor therapy due to their effectiveness and a more prevalent insensitivity toward tumor resistance mechanisms. Herein we describe the favorable properties of 6‐( N , N ‐dimethyl‐2‐aminoethoxy)‐11‐(3,4,5‐trimethoxyphenyl)pyrido[3,4‐ c ][1,9]phenanthroline (P8‐D6), a powerful inducer of apoptosis caused by an equipotent inhibition of human topoisomerase I and II activities. A broad‐spectrum effect against human tumor cell lines at nanomolar concentrations, as well as strong antileukemic effects, were shown to be superior to those of marketed topoisomerase‐targeting drugs and dual topoisomerase inhibitors in clinical trials. The facile four‐step synthesis, advantageous drugability properties, and initial in vivo data encourage the application of P8‐D6 in appropriate animal tumor models and further drug development.