1 Star2 Stars3 Stars4 Stars5 Stars (No Ratings Yet)
blankLoading...

Anthracyclines

Structure of the four main anthracyclines approved for clinical use

Structure of the four main anthracyclines
Structure of the four main anthracyclines

The anthracyclines are composed of a tetracyclic ring with adjacent quinone-hydroquinone moieties and a short side chain with a carbonyl group at C-13; an aminosugar is attached by a glycosidic bond to the C-7 of the tetracyclic ring. Doxorubicin (DOX) and daunorubicin (DNR) differ in the side chain terminus (-CH2OH or-CH3, respectively). Epirubicin (EPI) is obtained after an axial-to-equatorial epimerization of the hydroxyl group at C-4′ in the aminosugar. Idarubicin (IDA) is characterized by the absence of the methoxy group at C-4 in ring D.

Mechanisms of anthracycline-induced apoptosis of tumor cells

Mechanisms of anthracycline-induced apoptosis of tumor cells
Mechanisms of anthracycline-induced apoptosis of tumor cells

Mechanisms of anthracycline cardiotoxicity

Mechanisms of anthracycline cardiotoxicity
Mechanisms of anthracycline cardiotoxicity

One-electron (7 e~) reduction of the quinone moiety generates a semiquinone that recycles to the parent quinone by redox coupling with oxygen. The consequent cascade of superoxide anion (O2~), hydrogen peroxide (H2O2), and hydroxyl radical (‘OH), induces apoptosis through oxidative stress and gene suppression. Two-electron (2 e~) reduction of the side chain carbonyl group generates a secondary alcohol metabolite that also suppresses cardiac-specific genes and inactivates proteins of calcium and iron homeostasis. These mechanisms share multiple links and feedbacks.

Subscribe
Notify of
0 Comments
Inline Feedbacks
View all comments