Amsacrine (synonyms: m-AMSA, acridinyl anisidide) is an
antineoplastic agent.
It has been used in
acute lymphoblastic leukemia.
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 foll ...
into the
DNA of
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 differing in the position of the methoxy substituent group on the anilino-ring have little ability to poison topoisomerase II despite its intercalative behavior, suggesting that intercalation of the molecule in itself is insufficient to trap topoisomerase II as a covalent complex on DNA.
References
Sulfonamides
Antineoplastic drugs
IARC Group 2B carcinogens
Acridines
O-methylated phenols
DNA intercalaters
Topoisomerase inhibitors
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