Amsacrine (synonyms: m-AMSA, acridinyl anisidide) is an antineoplastic agent. It has been used in

acute lymphoblastic leukemia Acute lymphoblastic leukemia (ALL) is a cancer of the Lymphocyte, lymphoid line of blood cells characterized by the development of large numbers of lymphoblast, immature lymphocytes. Symptoms may include feeling tired, pale skin color, fever, ...

Mechanism

Its planar fused ring system can

intercalate Intercalation may refer to: *Intercalation (chemistry), insertion of a molecule (or ion) into layered solids such as graphite *Intercalation (timekeeping), insertion of a leap day, week or month into some calendar years to make the calendar follo ...

into the

DNA Deoxyribonucleic acid (; DNA) is a polymer composed of two polynucleotide chains that coil around each other to form a double helix. The polymer carries genetic instructions for the development, functioning, growth and reproduction of al ...

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

cells, thereby altering the major and minor groove proportions. These alterations to DNA structure inhibit both DNA replication and transcription by reducing association between the affected DNA and: DNA polymerase, RNA polymerase and transcription factors. Amsacrine also expresses

topoisomerase inhibitor Topoisomerase inhibitors are chemical compounds that block the action of topoisomerases, which are broken into two broad subtypes: type I topoisomerases (TopI) and type II topoisomerases (TopII). Topoisomerase plays important roles in cellular rep ...

activity, specifically inhibiting topoisomerase II. In contrast, the structurally similar o-AMSA, which differs only in the position of the methoxy substituent on the anilino ring, exhibits limited ability to poison topoisomerase II despite its intercalative properties. This suggests that intercalation alone is insufficient to stabilize topoisomerase II as a covalent complex on DNA.

References

Sulfonamides Antineoplastic drugs IARC Group 2B carcinogens Acridines O-methylated phenols DNA intercalaters Topoisomerase inhibitors {{antineoplastic-drug-stub