what is anticancer alkylating drugs # in details


Anticancer drugs:

Anticancer drugs are destroying the uncontrolled growth of the tissue or cell and modify the growth. Generally, most of the anticancer drugs are toxic in nature & many side effects are produced.

In 1940 nitrogen mustard are use for the treatment of malignancy, but rather many are discovered. To a in latest innovation are introduced the singling pathways, target growth factor, angiogenesis, etc.


anticancer alkylating drugs

anticancer alkylating drugs



Here, describes how cell generates (cell cycle)

G1 phase: to synthesis the general enzyme & cellular component that required for the DNA synthesis.

S phase: it’s also called to a s phase, in this phase DNA are synthesis.

G2 phase: to synthesis a protein & RNA, that useful for the cellular components.

M phase: it called to a mitotic phase, mitotic cell division takes place.

G0 phase: its also called a resting phase, the cell stops the dividing.

Classification of anticancer drugs :

Alkylating agents :

(a)    N mustard: chlorambucil, cyclophosphamide, mechlorethamine, melphalan.

(b)   Alkyl sulphonyl: busulphan.

(c)    Nitrosoureas: carmustine, lomustine, streptozocin.

(d)   Platinum-containing compounds : cisplatin, oxaliplatin, carboplatin.

(e)    Triazene: dacarbazine.

Antimetabolites :

(a)    Purine antagonist: 6 - thioguanine (6-TG), 6 - mercaptopurine (6-MP).

(b)   Folate antagonist: methotrexate.

(c)    Pyrimidine antagonists: 5 – fluorouracil, cytarabine.

Natural products :

(a)    Vinca alkaloid: vincristine, vinblastine.

(b)   Taxanes: docetaxel, paclitaxel.

(c)    Epipodophyllotoxins: teniposide, etoposide.

(d)   Antibiotics: mitomycin, bleomycin, actinomycin D, doxorubicin, daunorubicin.

(e)    Camptothecins: irinotecan, etoposide.

(f)     Enzymes : L – asparaginase.

Hormones & antagonist :

(a)    Progestin : hydroxyprogesterone caproate, medroxyprogesterone acetate.

(b)   Oestrogen: Ethinyl estradiol, fosfestrol.

(c)    Selective estrogen receptor down regulators : fulvestrant.

(d)   Selective estrogen receptor modulators : tamoxifen.

(e)    Androgens: testosterone propionate.

(f)     Aromatase inhibitors: letrozole, anastrozole.

(g)    Antiandrogen : flutamide.

(h)   5- alpha-reductase inhibitors : finasteride.

(i)     Corticosteroids: prednisolone & others.

(j)     GnRH analogs: goserelin, nafarelin, buserelin.am

NOTE:

antimetabolites, antibiotics, taxane, epipodophyllotoxin & vinca alkaloids, all drugs are act on dividing cell during cell cycle.

Alkylating agents, anticancer antibiotics & metal complex, drugs are acting on dividing as well as resting cells.

ALKYLATING AGENTS :

anticancer alkylating drugs


Alkylating agents are containing the alkyl group, these group are attached to a DNA base through a covalent bond. All alkylating drugs are act on the dividing as well as resting phase.

Simple mechanism of action of the alkylating group, Alkylating agents (not a platinum-containing compound) forms the high reactive carbonium ion, to a transfer the alkyl group to its various site on DNA. Result in inhibit DNA replication. To also a break the DNA strand & cell are death. Alkylating agent are also damage the protein.

NITROGEN MUSTARDS :

Cyclophosphamide :

To an active metabolites are derived from the phosphoramide mustard & acrolein. To cyclophosphamide are a prodrug that activates in the liver. Acrolein is responsible for hemorrhagic cystitis & phosphoramide mustards are produce a cytotoxic effect.

Its administered orally or i.v & excreted through a urine.

Adverse effect of cyclophosphamide is severe hemorrhagic cystitis. Its also side effect is dysuria & hematuria due to irritation of bladder mucosa by acrolein.

its also use for breast cancer, lymphomas  & chronic lymphocytic leukemia with other anticancer drugs. It’s a most powerful immunosuppressant. Hence, cyclophosphamide is useful for nephrotic syndrome & rheumatoid arthritis.

Mechlorethamine :

It’s also called to mustine HCl. Its first discovered drugs in nitrogen mustards. Its component of MOPP regimen (nitrogen mustards, oncovin, irritant drug & procanabazine.

To the adverse effect of mechlorethamine is nausea, vomiting & hemodynamic changes.

Chlorambucil :

Chlorambucil are the very slow-acting alkylating agents. Mainly active on the lymphoid series. Chlorambucil is the drugs that use for chronic lymphatic leukemia. It’s had some minor immunosuppressant property.

Melphalan :

Its also a used in ovarian cancer & also effective in multiple myeloma. Its major adverse effect is bone marrow depression. Also, another side effect like infection, diarrhea & pancreatitis are produced.

ALKYL SULFONATE :

Busulfan :

Its sensitive action for myeloid series & depress the bone marrow. Busulfan has preferred the drug for the chronic myeloid leukemia. The most common side effect is pulmonary fibrosis & pigmentation of skin.

NITROSOUREAS :

Carmusttine & lomustine are highly lipid-soluble alkylating agents with the very wide range of antitumor activity. Its effective in brain cancer & meningeal leukemia because of they cross the blood-brain barrier. To also a common adverse effect is nausea, vomiting, visceral fibrosis & renal damage.

PLATNUM CONTAINING COMPOAUNDS :                 

anticancer alkylating drugs


Cisplatin :

Cisplatin is a heavy metal complex; cisplatin drugs act on both dividing & resting cells. Cisplatin is forms a highly reactive platinum compound, that reacts with DNA & damages the DNA. The favored site is guanine residue N7. Its also react to the sulphonyl group of cytoplasmic & nuclear protein.

Cisplatin are administered through i.v. it's concentrated in the liver. Kidney, intestine & testes. The negligible amount is entering brain because Its very less amount are penetrating the blood-brain barrier & slowly excreted in urine with a half-life is 72 hrs. 

cisplatin is highly effective in the treatment of metastatic testicular & ovarian carcinoma, bladder & endometrial cancer. Its also used in head, neck, gastric, esophageal carcinoma.

Its most important toxicity is a renal impairment which depends on the dose administered. It can be reduced by proper hydration. Hypokalemia, hypomagnesemia, hypokalemia, tinnitus, deafness & sensory neuropathy are other problems produce. 

Neuropathy are commonly produced due to higher dose. Sometimes anaphylactic shock be produced. Cisplatin has a carcinogenic, teratogenic & mutagenic properties.

Carboplatin :

It’s a less reactive 2nd generation platinum-containing drugs. Its mechanism of action is similar to the cisplatin. Carboplatin better tolerated than cisplatin drugs. Nausea, vomiting, nephrotoxicity, ototoxicity & neurotoxicity are that side effect produce. Also, a liver dysfunction & thrombocytopenia adverse effect are produced.

Carboplatin are eliminated through urine by kidney & its half-life is 2-4 hours. It indicated in ovarian carcinoma, head & neck carcinoma, small cell lung cancer, etc. also indicates in breast cancer & seminoma.

Oxaliplatin :

Oxaliplatin is 3rd generation platinum-containing compound. Resistance is not easily developed to oxaliplatin & it retains activity against tumors that have to become resistant to cisplatin.

Its very effective in colorectal & gastric cancer. Also, a useful in gastroesophageal & pancreatic cancer. Peripheral neuropathy is an important side effect. Myelosuppression is a modest side effect, but diarrhea & acute allergic reactions are also producing.

So, this all details are anticancer alkylating drugs, generally cancer treatment is a very broad field, years by years it discovers the new treatment & therapy.