Alkylating antineoplastic agent


Alkylating antineoplastic agent

An alkylating antineoplastic agent is an alkylating agent that attaches an alkyl group to DNA.

Since cancer cells generally proliferate unrestrictively more than healthy cells do, cancer cells are more sensitive to DNA damage - such as being alkylated. 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" (e.g. cyclophosphamide).

Cyclophosphamide is one of the most potent immunosuppressive substances. In small dosages, it is 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 do not 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:

*Alkyl sulfonates
** Busulfan (ATC|L01|AB01)
*Ethyleneimines and methylmelamines
**Hexamethylmelamine or altretamine (ATC|L01|XX03)
**Thiotepa (ATC|L01|AC01)
*Nitrogen mustards
**Cyclophosphamide (ATC|L01|AA01)
**Mechlorethamine or mustine (ATC|L01|AA05)
**Uramustine or uracil mustard (no ATC code, PubChem|6194, DrugBank|APRD00130)
**Melphalan (ATC|L01|AA03)
**Chlorambucil (ATC|L01|AA02)
**Ifosfamide (ATC|L01|AA06)
*Nitrosoureas
**Carmustine (ATC|L01|AD01)
**Streptozocin (ATC|L01|AD04)
*Triazenes
**Dacarbazine (ATC|L01|AX04)
*Imidazotetrazines
**Temozolomide (ATC|L01|AX03)

*Platinum-based chemotherapeutic drugs (termed platinum analogues) destroy cells by alkylation. These include:
**Cisplatin
**Carboplatin
**Nedaplatin
**Oxaliplatin
**Satraplatin
**Triplatin tetranitrate

External links

* [http://pharmacology.unmc.edu/cancer/alkylate.htm University of Nebraska page on alkylating agent drugs]
*


Wikimedia Foundation. 2010.

Look at other dictionaries:

  • alkylating agent — n a substance that causes replacement of hydrogen by an alkyl group esp. in a biologically important molecule specif one with mutagenic activity that inhibits cell division and growth and is used to treat some cancers * * * a highly reactive… …   Medical dictionary

  • antineoplastic drug — noun any of several drugs that control or kill neoplastic cells; used in chemotherapy to kill cancer cells; all have unpleasant side effects that may include nausea and vomiting and hair loss and suppression of bone marrow function • Syn:… …   Useful english dictionary

  • antineoplastic — I noun any of several drugs that control or kill neoplastic cells; used in chemotherapy to kill cancer cells; all have unpleasant side effects that may include nausea and vomiting and hair loss and suppression of bone marrow function • Syn:… …   Useful english dictionary

  • alkylating agent — noun an antineoplastic drug used to treat some forms of cancer • Hypernyms: ↑antineoplastic, ↑antineoplastic drug, ↑cancer drug • Hyponyms: ↑chlorambucil, ↑Leukeran * * * noun : a substance that causes replacement of hyd …   Useful english dictionary

  • Antiarrhythmic agent — The cardiac action potential Antiarrhythmic agents are a group of pharmaceuticals that are used to suppress abnormal rhythms of the heart (cardiac arrhythmias), such as atrial fibrillation, atrial flutter, ventricular tachycardia, and ventricular …   Wikipedia

  • Hypolipidemic agent — Hypolipidemic agents, or antihyperlipidemic agents, are a diverse group of pharmaceuticals that are used in the treatment of hyperlipidemias. They are called lipid lowering drugs (LLD) or agents. Contents 1 Classes of hypolipidemic drugs 1.1… …   Wikipedia

  • Alkylation — Alkylating agent redirects here. For the class of drugs, see alkylating antineoplastic agent. Alkylation is the transfer of an alkyl group from one molecule to another. The alkyl group may be transferred as an alkyl carbocation, a free radical, a …   Wikipedia

  • Chemotherapy — A woman being treated with docetaxel chemotherapy for breast cancer. Cold mittens and wine coolers are placed on her hands and feet to reduce harm to her nails. Chemotherapy (sometimes cancer chemotherapy) is the treatment of cancer with an… …   Wikipedia

  • Dacarbazine — Systematic (IUPAC) name 5 (3,3 Dimethyl 1 triazenyl)imidazole 4 carboxamide Clinical data Trade names D …   Wikipedia

  • Busulfan — Systematic (IUPAC) name butane 1,4 diyl dimethanesulfonate …   Wikipedia


Share the article and excerpts

Direct link
Do a right-click on the link above
and select “Copy Link”

We are using cookies for the best presentation of our site. Continuing to use this site, you agree with this.