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.
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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 :
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 :
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.