Alkylating

Anticancers
What is Cancer ?
 Cancer is uncontrolled growth of abnormal
cells in the body. (cancer cells don’t die)
 There are over 100 different types of cancer,
and each is classified by the type of cell that
is initially affected.
 Cancer cells are also called malignant cells.
 Normal cells in the body follow an orderly
path of growth, division, and death.
 Programmed cell death is called apoptosis,

and when this process breaks down, cancer

begins to form.
 Unlikenormal cells, cancer cells do not
experience apoptosis and instead continue
to grow and divide. This leads to a mass of
abnormal cells that grows out of control.
Treatment
Types of cancer treatment
 Surgery

 Radiation therapy
 Monoclonal antibodies
 Hormonal therapy
 Stopthe synthesis of pre DNA molecule
building blocks e.g. folic acid and
nucleotides

These agents work to block some step in the

formation of deoxyribonucleotides or
nucleotides which are necessary in making of
RNA & DNA . So When these steps are blocked
, the nucleotides cannot be synthesized and
these cells cannot replicate .
 Examples: methotrexate , fluorouracil and
Mercaptopurine
 Directly damage the DNA in the nucleus of
the cell

These agents chemically damage DNA and

RNA. They disrupt replication of the DNA and
either totally halts replication or cause the
manufacture of nonsense DNA or RNA i.e. the
new DNA or RNA does not code
 Examples : alkylating agents (e.g.
Cisplatin) , and doxorubicin .
Alkylating agents
 Alkylating
agents are compounds that are
capable of introducing an alkyl group into
nucleophilic sites on DNA , RNA or any
enzyme through covalent bond .
 These agents are thought to react with the 7
position of guanine ( or any other nitrogen
base) in each of the double strands of DNA,
causing cross-linking that interferes with
separation of the strands and prevents
mitosis.
 Thefavored site on DNA is at the N7 position
of guanine, adenine, cytosine, and even the
sugar phosphate groups .
Platinum based alkylating like agents
 Cisplatin
 Carboplatin
 Oxaliplatin

Methylhydrazines
 Procarbazine
Mechanism of Alkylation
 Methclorethamine (2-chloro-N-(2-chloroethyl)-
N-methyl-ethanamine)

 Is taken By IV infusion and It used

to treat prostate cancer .
 Cyclophpsphamide (Cytoxan®)
 Cyclophosphamide (N,N-bis(2-chloroethyl)-
1,3,2-oxazaphosphinan-2-amine 2-oxide)

 Thismost widely used

Alkylating agent
Alkyl sulphonates
 Busulfan (butane-1,4-diyl dimethanesulfonate)
(Myleran®)
 It
is used for treatment of
chronic myelogenous leukemia
(CML) in bone marrow
Transplantation patients
 Cisplatin (diamminedichloroplatinum)

 thepreferred site of binding

is the N7 position of guanidine
Methylhydrazines
 Procarbazine (N-isopropyl-4-[(2-
methylhydrazino)methyl]benzamide)