ROS-activatable Prodrug of Doxazolidine as Novel Cancer Therapy Paradigm.

ABSTRACT: Overcoming severe side effects from anticancer agents without decreasing their effects on tumor growth is a major challenge. We report on a prodrug technology using agents that are spatiotemporally activated primarily in tumors while the extratumoral toxicity to healthy cells is minimized. We developed ROS-activatable prodrugs of a strong anticancer agent, doxazolidine (doxaz). Doxaz is a DNA alkylating agent with a half-life of 3 min and significantly higher cytotoxicity than the clinically used parental compound doxorubicin (dox). Importantly, doxaz is not affected by p-glycoprotein expression since it irreversibly alkylates DNA while dox inhibits the topoisomerase II DNA complex. As drug activator, we use reactive oxygen species (ROS), already produced inside cancer cells in higher abun

SUBMITTER: Tamura R 

PROVIDER: S-EPMC12781957 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature