Novel N,N-Dimethyl-idarubicin Analogues Are Effective Cytotoxic Agents for ABCB1-Overexpressing, Doxorubicin-Resistant Cells.

ABSTRACT: Anthracyclines comprise one of the most effective anticancer drug classes. Doxorubicin, daunorubicin, epirubicin, and idarubicin have been in clinical use for decades, but their application remains complicated by treatment-related toxicities and drug resistance. We previously demonstrated that the combination of DNA damage and histone eviction exerted by doxorubicin drives its associated adverse effects. However, whether the same properties dictate drug resistance is unclear. In the present study, we evaluate a library of 40 anthracyclines on their cytotoxicity, intracellular uptake, and subcellular localization in K562 wildtype versus ABCB1-transporter-overexpressing, doxorubicin-resistant cells. We identify several highly potent cytotoxic anthracyclines. Among these, N,N-dimethyl-

SUBMITTER: van Gelder MA 

PROVIDER: S-EPMC11345819 | biostudies-literature | 2024 Aug

REPOSITORIES: biostudies-literature