ArticleMolecular pharmaceutics2026
Syntheses, Biological and Preclinical Evaluations, and Nanoparticle Formulations of the ROS-Activatable Prodrugs of Doxazolidine for Drug-Resistant Cancer Therapy.
Article in Molecular pharmaceutics, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.
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Abstract
Doxorubicin (dox) has been used for the treatments of many cancers for more than 50 years since its discovery. Currently, the treatment with dox is often limited by cardiotoxicity and the development of drug resistance. Doxazolidine (doxaz) is a dox-formaldehyde conjugate discovered in the 1990s. It bears an extra carbon, linking its daunosamine hydroxyl to that adjacent amino substituent to create an oxazolidine ring. In contrast to dox, which is a topoisomerase inhibitor, doxaz cross-links DNA to nonspecifically inhibit cell growth. Doxaz is significantly more cytotoxic than dox, even against the dox-resistant cancer cells, and in spite of its 3-minute half-life for hydrolysis to dox. Doxaz has been studied since its discovery, but not clinically, due to its cytotoxicity and unsuccessful attempts to generate the prodrugs of doxaz that are activated solely in cancer cells without damaging healthy normal cells. Here, we report an ROS-activatable prodrug of doxaz, named Doxaz-BA, formulated as a nanoparticle. We synthesized Doxaz-BA and its derivatives and tested them as nanoparticle formulations
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