Everything about Alkylating Antineoplastic Agent totally explained
An
alkylating antineoplastic agent is an
alkylating agent that attaches an alkyl group to
DNA.
Since
cancer cells generally proliferate unrestrictively more than do healthy cells they're more sensitive to DNA damage, and alkylating agents are used clinically to treat a variety of tumours.
Agents acting nonspecifically
Some alkylating agents are active under conditions present in cells; and the same mechanism that makes them toxic allows them to be used as anti-cancer drugs. They stop tumour growth by cross-linking
guanine nucleobases in
DNA double-helix strands - directly attacking DNA. This makes the strands unable to uncoil and separate. As this is necessary in DNA replication, the cells can no longer divide. These drugs act nonspecifically.
Agents require activation
Some of them require conversion into active substances
in vivo (for example
cyclophosphamide).
Cyclophosphamide is one of the most potent immunosuppressive substances. In small dosages, it's very efficient in the therapy of systemic lupus erythematosus, autoimmune
hemolytic anemias,
Wegener's granulomatosis and other
autoimmune diseases. High dosages cause
pancytopenia and hemorrhagic
cystitis.
Dialkylating agents, limpet attachment, and monoalkylating agents
Dialkylating agents can react with two different 7-N-guanine residues and if these are in different strands of DNA the result is
cross-linkage of the DNA strands, which prevents uncoiling of the DNA double helix. If the two guanine residues are in the same strand the result is called
limpet attachment of the drug molecule to the DNA.
Monoalkylating agents can react only with one 7-N of guanine.
Limpet attachment and monoalkylation don't prevent the separation of the two DNA strands of the double helix but do prevent vital DNA processing
enzymes from accessing the DNA. The final result is inhibition of cell growth or stimulation of
apoptosis, cell suicide.
Examples
In the
Anatomical Therapeutic Chemical Classification System, alkylating agents are classified under
L01A.
Alkylating agents activated by cytochrome p-450:
Other selected examples:
Further Information
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