biostudies-literatureUnknown15(1)Walunj DModifying existing drugs to enhance their activity and reduce toxicity is a major focus of drug development. We developed a novel class of dual-action chimeric molecules for cancer therapy, linking known drugs to a DNA-methylating monomethyl triazene moiety (azene) via nucleophilic substitution. In-vitro screening of these chimeras on various leukemia cell lines identified a potent chimera, doxorubizen, a sequel of the known DNA intercalator and topoisomerase 2 (Topo-II) inhibitor doxorubicin (Dox) and azene. Molecular docking and dynamic simulations showed doxorubizen as a more potent Topo-II inhibitor than Dox as it binds to major grooves in DNA. Moreover, the monomethyl triazene portion is positioned favorably through tetracene core intercalation, potentially facilitating methylation atScientific reports10607https://www.ebi.ac.uk/biostudies/studies/S-EPMC11950436biostudies-literatureNovel dual action chimera doxorubizen demonstrates superior efficacy to doxorubicin in acute leukemia.PMC11950436Hershkovitz-Rokah OWalunj DMitra PBazylevich AMuddineni SSNATkachenko IMilyavsky MGellerman GTobi DZipin-Roitman AEgarmina KShpilberg OfalseNovel dual action chimera doxorubizen demonstrates superior efficacy to doxorubicin in acute leukemia.Modifying existing drugs to enhance their activity and reduce toxicity is a major focus of drug development. We developed a novel class of dual-action chimeric molecules for cancer therapy, linking known drugs to a DNA-methylating monomethyl triazene moiety (azene) via nucleophilic substitution. In-vitro screening of these chimeras on various leukemia cell lines identified a potent chimera, doxorubizen, a sequel of the known DNA intercalator and topoisomerase 2 (Topo-II) inhibitor doxorubicin (Dox) and azene. Molecular docking and dynamic simulations showed doxorubizen as a more potent Topo-II inhibitor than Dox as it binds to major grooves in DNA. Moreover, the monomethyl triazene portion is positioned favorably through tetracene core intercalation, potentially facilitating methylation at2025-01-01T00:00:00Z2025 Mar2026-06-01T22:59:36.908Z2025-07-13T03:04:30.887ZS-EPMC119504364014843910.1038/s41598-025-94373-8