One of the first to use bis- (beta-chloroethyl) amine derivatives as antitumor agents.
The reason for the use of these compounds was the data obtained in the 40s of the XX century. during the Second World War, when the effect on the body of chemical warfare agents was studied in detail: mustard gas (or bis-beta-chloroethyl sulfide) and nitrogen mustard gas (or trichlorethylamine). Earlier, in 1919, it was established that nitrogen mustard gas causes severe leukopenia and bone marrow aplasia. Further studies showed that nitrogen mustard gas has a specific cytotoxic effect on lymphoid tissues and has antitumor activity in lymphosarcoma in mice. Clinical trials of trichlorethylamine began in 1942, marking the beginning of the era of modern tumor chemotherapy.
Currently, less toxic derivatives of bis- (beta-chloroethyl) amine (sarcolysin, chlorambucil, cyclophosphamide, embihin, etc.) are used in medical practice. Following bis- (beta-chloroethyl) amines, cytostatic alkylating compounds of other chemical groups were obtained: ethyleneimines and ethylenediamines (thiophosphamide), alkylated sulfonates, derivatives of methanesulfonic acid (busulfan), triazenes, platinum preparations, nitrosoureas (lomustine, carmustine, nitroso, fotymustine ) and etc.
The mechanism of the antitumor action of platinum derivatives (carboplatin, cisplatin) is associated with the ability to bifunctional alkylation of DNA strands, leading to long-term suppression of nucleic acid biosynthesis and cell death.
Platinum derivatives are not specific for the cell cycle, they act in the G0 phase, at the first stage they inhibit the synthesis of DNA, RNA and protein, and at the second stage metabolic products are formed that act only on DNA synthesis.
The appearance of platinum derivatives in the late 70s of the last century significantly changed the understanding of the possibilities of chemotherapy for malignant neoplasms.
Medicines from the group of nitrosourea derivatives also have a wide spectrum of cytotoxic activity. The antitumor effect (cyclo- and phase-specific) is due to the transfer of alkyl groups to the nucleophilic centers of DNA, RNA, proteins and the alkylation of their molecules, which leads to the death of the tumor cell. A distinctive feature of this group of drugs is their ability to pass through the BBB and the absence of cross-resistance with derivatives of chloroethylamines and ethyleneimines. They are effective in primary and metastatic tumors of the brain and spinal cord.
Derivatives of methanesulfonic acid (busulfan, etc.), used in exacerbations of chronic myeloid leukemia, undergo intramolecular cyclization with the formation of an ethyleneimine ion capable of transferring an alkyl group to cellular structures directly or through the formation of a carbocation. They act in the first half of the G1 phase, at the beginning and at the end of the S and G2 phases, synchronizing the phases of the cell cycle of cancer cells. The highly reactive groups of busulfan form strong covalent bonds with the nucleophilic centers of DNA and RNA. At the same time, DNA turns and spirals are stitched together, the possibility of its replication is lost, chain breaks occur, mitotic blocks occur, mutations become more frequent.
Along with a specific inhibitory effect on tumors, alkylating compounds, like other antineoplastic agents, act on other tissues and systems of the body, which causes their side effects. One of the main side effects is a depressing effect on hematopoiesis as a result of interaction with nucleoproteins of the cell nuclei of hematopoietic tissues. There is leukopenia, thrombocytopenia, anemia, which requires special attention and precise regulation of doses and regimen of drugs. In order to increase the effectiveness and tolerance of anticancer drugs, additional drugs are used. So to stimulate hematopoiesis, cytokines are used – granulocyte-macrophage and granulocyte colony-stimulating factors (filgrastim, molgramostim), as well as a number of interleukins and erythropoietin. It should be borne in mind that the inhibition of hematopoiesis increases with combined treatment regimens – a combination of several anticancer drugs, radiation therapy, etc.
With the use of chloroethylamines, platinum derivatives, nausea, vomiting, loss of appetite, and diarrhea are often observed. To stop these effects, antagonists of serotonin 5-HT3 receptors and blockers of dopamine D2 receptors are used. In contact with the skin and mucous membranes, an irritating effect and the development of abscesses are possible, with the introduction of solutions under the skin, tissue necrosis is possible.
One of the characteristic features of anticancer drugs is their immunosuppressive effect, which can weaken the body’s defenses and facilitate the development of infectious complications. To prevent possible infections caused by suppressed immunity, antibiotics may be used.
It should be noted that the use of alkylating compounds, like other anticancer drugs, is carried out only as directed by an oncologist and in a specialized medical institution. Depending on the characteristics of the disease, its course, the effectiveness and tolerability of the anticancer drugs used, the scheme of their use, doses, combination with other drugs may change.
Below is a list of alkylating agents:

  • Arabinopyranosyl methyl nitrosourea
  • Aziridinylmethylthiazolidinylphosphine oxide
  • Bendamustine
  • Busulfan
  • Carboplatin
  • Carmustin
  • Chlorambucil
  • Cisplatin
  • Cyclophosphamide
  • Dakarbazine
  • Dibrospidium chloride
  • Fotemustin
  • Ifosfamide
  • Lomustin
  • Melphalan
  • Nimustin
  • Oxaliplatin
  • Procarbazine
  • Prospidium chloride
  • Sarcolysin
  • Temozolomide
  • Tiotepa
  • Treosulfan