Hydroxylation at C-3′ of doxorubicin alters the selected phenotype of cellular drug resistance

Hydroxylation at C-3′ of doxorubicin (DOX) yields the uncharged congener hydroxyrubicin, which circumvents P-glycoprotein-mediated drug resistance without loss of topoisomerase II inhibitory activity. Hydroxyrubicin-resistant cells exhibit a phenotype that is uniquely different from DOX resistance by expressing non-functional P-glycoprotein and hypersensitivity to anti-mitotic drugs.