Structural Biochemistry/Amsacrine

Amsacrine

Description

Amsacrine C₂₁H₁₉N₃O₃S

Amsacrine is a potent intercalating antineoplastic agent. It is effective in the treatment of adult acute leukemias and malignant lymphomas, but not effective in the treatment of solid tumors. It is frequently used in combination with other antineoplastic agents in chemotherapy.

Usage

Injectable (Intravenous Route)

Side Effects

• Black stools
• cough or hoarseness
• fever or chills
• painful or difficult urination
• pinpoint red spots on skin
• sores, ulcers, or white spots on lips, tongue, or inside mouth
• Abdominal pain or tenderness
• blurred vision
• fast, pounding, or irregular heartbeat or pulse
• palpitations
• seizures
• yellow eyes or skin

Mechanism of Actions

Inhibition of Topisomerase

Complex of DNA-Topoisomerase is destroyed

The DNA is wound around basic proteins called histones and is tighly coiled or supercoiled. Sequences of DNA must be unwound or relaxed before they can be processed by DNA processing enzymes. Topoisomerase II or TopoII is one enzyme that can process DNA. TopoII temporarily breaks the DNA strand and allows both ends to freely rotate within the enzyme. This allows the DNA to unwind. After the DNA is processed, the enzyme then reconnects the two ends.

Amsacrine kills cancerous cells by inhibiting the Topo II enzyme. It stabilizes the enzyme with the broken DNA strand complex long enough for the enzyme-DNA complex to break down completely. When the DNA is destroyed, the cancerous cells will be eventually killed.

References

"Amsacrine." Scott Hamilton CARES Initiative. N.p.. Web. 07 Dec 2012. <http://chemocare.com/chemotherapy/drug-info/Amsacrine.aspx> Grove, WR, CL Fortner, and PH Wiernik. "Clinical Pharmacy." Clinical Pharmacy. Jul-Aug. (1982): 320-26. Print.