The document discusses antineoplastic agents (anticancer drugs) and provides information on cancer and its diagnosis and treatment. It defines cancer as uncontrolled cell growth and discusses how cancer is classified. It also summarizes some common cancer types in children and adults. The document outlines several methods used to treat cancer, including surgery, radiation therapy, immunotherapy, hormonal therapy, chemotherapy and antibiotics. It provides classifications of antineoplastic drugs and examples.

1. ANTINEOPLASTIC AGENTS
(anticancer drugs)
P.Ravi sankar
M.pharm.,(Ph.D.,)
Vignan pharmacy college,
Vadlamudi
Prof.P.Ravisankar
Vignan Pharmacy college
Valdlamudi
Guntur Dist.
Andhra Pradesh
India
banuman35@gmail.com
0091 9059994000.
simbolizes Fight
against breast cancer

3. Cancer is a disease characterized by
uncontrollable, irreversible, independent,
autonomous, uncoordinated and relatively
unlimited and abnormal over growth of tissues.
•Cancer is not a single disease. It is a group of more than 200
different diseases.
•Cancer may spread to other parts of the body.
• currently 1 in 4 deaths in USA are due to cancer.
• 1 in 17 deaths are due to lung cancer.
•An estimated 2,22,520 people diagnosed lung cancer in the
United States in 2010.
•Lung cancer is the most common cancer in men.
•Breast cancer is the most common cancer in women.
• Around 15 lakh new cases are diagnosed every year in india.
• A total of 15,96,670 new cancer cases and 5,71,950 deaths from
cancer are projected to occur in the United States in 2011.
What is Cancer?

4. Introduction and History
•
• The medical term for tumor (or) cancer is Neoplasm, which means a relatively
autonomous growth (or) un corodinated cell proliferation of body tissue.
• The term Neoplasm means New growth and the process of cell proliferation is
called Neoplasia.
• The branch of medicine which deals with the excessive study of neoplasm
(tumor) and its development diagnosis and treatment is called “Oncology.”
• For the first time Hippocrates coined the Greek word Karkinos i.e. (crab/cray
fish) for malignant breast cancer. (because enlarge or swollen veins around them
resembled the limbs of crab).
• The term cancer was translated from a Latin word
carcino i.e. Crab by celsus.
• Galen used ‘oncos’ to describe all tumors, the root
of the modern word ‘oncology’.

5. Malignant tumours can
spread from the original site and
cause secondary tumours. This is
called metastasis. They interfere
with neighbouring cells and can
block blood vessels, the gut,
glands, lungs etc.
Malignant tumors can also destroy
the correct functioning of major
organs.
Non-Malignant tumor
(or) benign tumor
(or) also known as
non-cancerous tumor which
does not metastasize.
Benign tumors are not usually a threat to
life. Benign tumors generally are confined
to one area.
classified
in to two
categories
If the cancer is localized
It is said to be benign.
If the cancerous cells invade
The other parts of the body
And set up secondary tumors
A process known as metastasis.

6. Examples of Benign Tumors
Papilloma - A projecting mass on the skin (for example, a wart)
Adenoma - A tumor that grows in and around the glands
Lipoma - A tumor in fatty tissue
Osteoma - A tumor originating in the bones
Myoma - A tumor of muscle tissue
Angioma - A tumor usually composed of small blood or lymph vessels (for example, a
birthmark)
Nevus - A small skin tumor of one variety of tissues (for example, a mole).
Most Common Cancers in Children and Adults
Children Adults
Leukemias: acute lymphocytic (lymphoblastic)
almost one-third of all childhood cancers.
Lung
Brain and Other nervous system tumor:
neuroblastoma
Breast (carcinoma)
Lymph-node cancers (lymphomas) Colorectal
Bone (osteosarcoma) Prostate
Soft-tissue sarcomas: rhabdomyosarcoma Skin (melanoma)
Kidney: Wilms tumor
Eye: retinoblastoma
Adrenal gland (adrenocortical carcinoma)

7. • How is cancer classified?
• There are five broad groups that are used to classify cancer.
• Carcinomas are characterized by cells that cover internal and
external parts of the body such as lung, breast, and colon cancer.
• Sarcomas are characterized by cells that are located in bone,
cartilage, fat, connective tissue, muscle, and other supportive
tissues.
• Lymphomas are cancers that begin in the lymph nodes and immune
system tissues.
• Leukemias are cancers that begin in the bone marrow and often
accumulate in the bloodstream.
• Adenomas are cancers that arise in the thyroid, the pituitary gland,
the adrenal gland, and other glandular tissues.

9. The tumour cells generally divide faster then the normal cells, nucleic acid synthesis
Is faster and so tumour cells need more of the nucleic acid building blocks.
The tumour cells need more than their fair share of the building blocks and
Accumulate the cytotoxic drug contain nucleophiles(disrupting the
Function of DNA directly.) more effectively.
The combination therapy(the simultaneous use of various anticancer drugs with
Different mechanism of action) is more effective than using a single drug.
Advantage is increased efficiency of action and decreased toxicity.
Since the cancer cells are derived from the normal cells identifying target
That are unique to cancer cells is not easy.
As a result traditional anti cancer drugs act against targets which are present
In both types of cell.
There fore the effectiveness and selectivity of such drugs is dependent on them
Becoming more concentrated in cancer cells than normal cells. Cancer cells are
Generally growing faster than normal cells.so they accumulate nutrients, synthetic
Building blocks and drugs more quickly.
Unfortunately not all drugs grow rapidly. Cells in the Centre of the tumour may be
Dormant.
Generally bone marrow cells,hair roots grow rapidly as a result they too accumulate anticancer
Drugs,resulting Bone marrow toxicity is common side effect of cancer chemotherapy.
Resulting weakening of the immune system and decreased resistance to infection.
If the cancer patients are infectious such secondary infections can be difficult to treat.
Antibacterial drugs may not be effective as they rely on the normal functioning
Of the immune system.
Other side effects of anti cancer drugs are impaired wound healing, loss of hair,
Damage to the epithelium of GIT,depression of growth in children, sterility,
nausea, kidney damage.

10. Largest tumor ever removed
• According to Guinness World Records, the
biggest tumor ever removed intact from
the human body weighed in at 303
pounds (137.6 kg) and measured
• 3 feet (1 m) in diameter.
• The tumor, located on the right ovary,
was removed in 1991 during an operation
performed by Professor Katherine
O’Hanlan at Stanford University
Medical Center in California.
• The operation to remove the tumor from
the abdomen of an unnamed 34-year-
old woman took over six hours
to complete.
• The pathology report concluded that
fortunately the tumor was benign. The
patient made a full recovery, and
reportedly did not seek treatment sooner
due to being bed-ridden and suffering
from agoraphobia (fear of open spaces).

11. China’s elephant man grows world’s
Largest tumor on face.
(50 pounds)
The man-with-no-face.
"CHILDREN see me and start crying," Jose
Mestre mumbles sadly from behind the
monstrous 12lb growth that is eating his
face.
51-year-old, from Portugal.
Carer ... sister Guida looks after
him.
Huang Chuncai
A Chinese man recovers from surgery that
removed part of his facial tumors, which
weigh more than 20 kilograms in total.
(32 yearys old)

12. Burkitts lymphoma.
Multile myeloma
Osteoporosis is most common
Acute leukemia
blood cancer
Breast cancer
Mucosal cells of
rectum
Are all cancers tumors?
Yes other than blood cancer.
In which part of the body cancer can’t occur?
Those having dead or non living parts of hair(other than roots)
Tooth enamel,nails (non living part)

13. Tumor growth and kinetics
• The principle difference between mature of
normal tissue and tumors is …
• The rate of cell replication i.e. proliferation for
most normal tissues equals the rate of cell death
(a balance is maintained between cell renewal
and cell apoptosis (programmed cell death),
where as in neoplasm proliferation exceeds the
cell death.
• Proliferation in normal tissue responds to subtle
signals that indicate when proliferation is
needed repair, regeneration or growth and
development.
• But ...Neoplasm seem to lack such an auto
regulation of proliferation and the cell
replication rate i.e. new cells replace the old cells
by differentiation mechanism.

14. Doubling time
• The doubling time is the mean (“average”) interval between
successive mitoses.
• It is a characteristic of the particular type of tumor cell.
Doubling time varies markedly among various kinds of
tumors.
• Burkitt’s tumor = it is approximately 24 hours.
• In acute leukemia = 2 weeks.
• In breast cancer = 3 months.
• In multiple myeloma = 6 to 12 months.
• Mucosal cells of the rectum every 24 hours.
• A tumor cell becomes detectable when the number of cells
reaches about 109
to 10 10
cells. This requires 30 to 33
doubling times.
• The neoplasm becomes lethal when the population reaches
about 5x1011
to 5x1012
cells, after 39 to 42 doubling times.

15. Cocontact inhibition
Little bit defect cell
As the tissue growing human cells
replicates Perfect copies of each
other(Mitosis)
One of the cell Replicates little bit faster
A change in the DNA sequence with in a gene or
chromosome

16. Cells that are old or not functioning properly normally self destruct
and are replaced by new cells.
However, cancerous cells do not self destruct and continue to
divide rapidly producing millions of new cancerous cells.

17. Occasionally due to carcinogens
(cancer causing agents) one of the
Cell get mutated and does not
respond to normal growth
control mechanisms.
This mutated cell undergoes further
mutations and transforms i.e.
to Converts in to tumor cell which
starts proliferating vigorously. This in
turn results in a mass of abnormal
cells (tissues) called tumour
Or neoplasm.
Persons with
hereditary cancer
already have the
first mutation.Replicating like crazy.
Broken DNA replication
DNA mutations.

18. SIGNALS LEADING TO APOPTOSIS

19. (
As the tumor cell
grows it require a
Steady supply of
aminoacid,
carbohydrates,
oxygen,nucleic
acid bases,and
growth factors.
Vascular endothelial
growth factor,
fibroblast growth
factor
Interacts
with
receptors
stimulate
Leading to the branching
And extention of
Capillaries process known as
ANGIOGENESI
S
Vascular growth factors are present in normal cells these are released when tissue has
been damaged. Angiogeness helps in the repair of injured tissues and is controlled by
Angiogenisis inhibitors( angiostatin and thrombospondin)
Unfortunately this balance is disturbed in tumour growth.
Newly developing endothelial cells
Release protein
stimulates

20. When a cell breaks away from the
tumor, it can be swept into the
lymph system or the bloodstream
and be carried to other parts of the
body where new tumors can
(Vascular endothelial growth factor and fibroblast factor FGF2)
And FGF2.

21. CAUSES OF CANCER
• There are several agents responsible for cancer
The agents (physical, chemical and biological) which causes cancer are called carcinogens.
1 Physical agents: Uv and ionizing radiations (x-ray, gamma and alpha and beta rays cause
cancer, uv rays of sunlight, nuclear fission. These radiations have mutagenic effect.
Ex: Leukaemias, skin, lung, breast, osteosarcoma, thyroid cancer.
2. Biological agents:
a. Bacterial agents: peptic ulcers and chronic gastritis and if these are left untreated for a
long time leads to gastric cancer.
b. Fungal agents: The fungus Aspergillus flavus releases aflatoxins in stored food and
grains .If this contaminated food is consumed (espicially by Hepatitis B virus infected
patients) it leads to hepatocellular carcinoma.
c. Viral agents: Cervical cancer,Burkitt’s lymphoma,hairy cell lukaemia,Haepatic
carcinoma.
3. Chemical agents: Alkylating agents, The acylating agents, Polyaromatic hydrocarbons,
Aniline, arsenic, Anthracenes, dimethylsulphate,diepoxybutane,acetyl imidazole,
dimethyl carbamyl chloride.
carcinogens like nicotine,asbestos,coaltar,benzene,aniline dyes.
4. Genetic factors: Genetic inheritance plays a key role in causing some of the cancers (breast
carcinoma,retino blastinoma.
5. Diet and habits: People taking rich in fats, low fibre content and stored grains.
Alcoholism, smoking, chewing tobacco and betel nut .(pan,masala,Gutka)
6. Hormones and Drugs: Taking excessive oestrogens during the times of pregancy(Vaginal
endometrial cancer is prevalent in the girls born to the mothers)

22. • 7.Epidemiological factors:
a. Geographical and Racial factors:
Climate, soil, diet habit and customs etc. Genetic
composition also influence the variations in cancer.
Ex: Breast cancer in prevalent in American women.
Gastric carcinoma is in Japanese.
b. Environmental and cultural factors: Exposure to industrial
contaminants, smoke and radioactive metals.
Cancer of penis is very rare in Muslims and jews due to the
custom of circumcision and their female partners are less
likely to suffer(prone) to cancer of cervix.
c. Age and sex: High risk of cancer is incident at an older age
due to reduction in immunity. It is usually seen in 5th
decade of life.
Men are more prone to lung cancer while women are
susceptible to breast cancer.

23. ANTINEOPLASTIC AGENTS
• Antineoplastic agents are the drugs which are used in to
management of malignant disease (i.e. cancer)
• Antineoplastic agents are also known as Cytotoxic agents.
cancer is a very difficult disease to treat. This has been because of
lack of reliable diagnostic tests for the early detection and not
having the compounds which will cure any form of cancer.
Anticancer drugs used in the treatment of malignant disease when
surgery or radiotherapy is not possible or has proved ineffective.
They are also employed as
adjunct to surgery or Radiotherapy. They are used as
the initial treatment as in laeukaemia.
Chemotherapy usually involves combinations of drugs having
different targets or mechanisms of action.Traditional anticancer
drugs are generally cytotoxic(toxic to the cells) and the more
modern drugs are selective in their action.

24. How is cancer diagnosed and staged?
Early detection of cancer can greatly improve the odds of successful treatment
and survival. Physicians use information from symptoms and several other
procedures to diagnose cancer.
Common tests include Common tests include the following:
Biopsy of the tumor
Blood tests (which look for chemicals such as tumor markers)
Bone marrow biopsy (for lymphoma or leukemia)
Chest x-ray
Complete blood count (CBC)
CT scan
MRI scan (magnetic resonance imaging)
Extracting cancer cells and looking at them under a microscope is the only
absolute way to diagnose cancer. This procedure is called a biopsy.
Physicians will analyze your body's sugars, fats, proteins, and DNA at the
molecular level.
For example, cancerous prostate cells release a higher level of a chemical
called PSA (prostate-specific antigen) into the bloodstream that can be
detected by a blood test.

25. TREATMENT OF CANCER• Cancer can be treated by the following means:
• 1. Surgery
Robotic radical prostatectomy for prostate cancer.
(3-D) view of the surgical field, at a greatly
increased magnification, up to 15 times greater than the human eye.
2. Radiation therapy.
• 3.Immunotherapy.
• 4.Hormonal therapy.
• 5.Antibiotics.
• 6.Chemotherapy.
Chemotherapy is the term applied for a wide range of chemical
substances i.e. drugs that are employed in the treating the cancer.
These drugs may act by various mechanisms like
Interfering with the replication of DNA.
Inhibiting the formation of important molecules which are needed for
DNA formation and inhibiting the mytotic spindle.

26. Infact, most of traditional Anticancer agents now-a- days
available
which increase survival time.
• supress the growth of developing neoplasm
• sprerading of the disease from one place to another place.
• Relief of pain upto some extent
• Immunosuppressive agents are also used to prolong the life of
organs and tissue transplants during surgical procedural methods
in cancer.

27. Classification of Antineoplastic drugs
• Cytotoxic drugs:
• A. Alkylating agents :
1.Mustard drugs: Mechlorethamine, Chlorambucil, Cyclophosphomide, Melphalan .
2. Aziridines : Thiotepa.
3. Alkyl sulphones: Busulphan.
4. Nitrosoureas : Lomustine, Carmustine.
Procarbazine
B.B. AntimetabolitesAntimetabolites::
Purie antagonists:Purie antagonists: 6-Mercaptopurine.
Folic acid antagonist:Folic acid antagonist: Methotrexate.
Pyrimidine antagonist:Pyrimidine antagonist: 5-Fluorouracil.
C.C. Plant productsPlant products: 1. Vinka alkaloids: 1. Vinka alkaloids
a.a. Vincristine b. Vinblastine..
2.Taxanes:2.Taxanes: PacliPaclitaxel,taxel, DoceDocetaxel.taxel.
D.D. AntibioticsAntibiotics: Dactinomycin, Daunorubicin, Doxorubicin, Mitomycin.: Dactinomycin, Daunorubicin, Doxorubicin, Mitomycin.
E.E. RadioisotopesRadioisotopes: Radioiodine I: Radioiodine I131131
, Radiophosphorus P, Radiophosphorus P3232
..
F. Other cytotoxic drugsF. Other cytotoxic drugs: Hydroxyurea, cisplatin.: Hydroxyurea, cisplatin.

28. Mechanism of actions of anticancer agents

29. Alkylating agentsAlkylating agents ::
1.Mustard drugs1.Mustard drugs : Mechlorethamine,: Mechlorethamine, Chlorambucil,Chlorambucil, Cyclophosphomide, MelphalanCyclophosphomide, Melphalan
Nitrogen mustards get their name because they are related to the
sulfur-containing mustard gases used during First world War.
cyclophosphomide
Launcher
CH3
Missile
(odour resembling mustard,garlic plant hence the name given)
It is a prodrug and not toxic it self. Metabolism in the liver by cytochrome p450 enzyme
Oxidizes the ring.ring open takes place and generate the cytotoxic
Alkylating agent.
Unfortunately acrolen
Is toxicity to the kidneys
And blader and results in inflammation
Odema,bleading,ulceration

30. Alkylating agents
Contains ractive alkyl
Groups .These compounds
undergoes neibhobouring
group reactions
Produce highly reactive
Carbonium ion intermeadiates
Which form covalent bonds
By alkylation at 7th
Position of guanine in each of
The double starnds of DNA
Causing cross
linking/mispairing.
This interferes in the
separation
of strands and prevents
mitosis or arrest cell
replication.
Alkylating agentsAlkylating agents
Mechanism of action
Alkylation is defined as replacement of hydrogen on an atom by an
alkyl group.
nu - H + alkyl-Y ---------- nu-alkyl + H+
+ Y-
(highly electrophilic
compounds)

31. Undergoes neibhobouring group reactions to
form Stained 3 membered onium , ethylene
imminium ion or
Aziridinium ions,which react with guanine
groups on DNA To produce cross-linking.
If second alkyl halide reacts with
Water Cross linking is the major factor
First alkylating agent used medicinally
Displaces chloride ion
Highly electrophilic ion
Alkylation of DNA
Process can be repeated

32. After forming highly electrophilic aziridinium ion. Alkylation of DNA can takes
Place. Since the process can be repeated.
Cross linking b/n chains or within the one chain will occur.
Monoalkylation of DNA guanine units is also possible.
If second alkyl halide reacts with water cross linking is the major factor.(no inhibition
Of replication,and these drugs doesn’t act as antineoplastic agents.
Chlormethine is highly reactive and can react with water,blood and tissues.
It is too reactive to survive the oral route and has to be administered I.V.
It is mainly used for Hodgkin’s lymphoma.
The side reaction mention above can be reduced by lowering the reactivity of
Alkylating agent.
Putting aromatic ring on the N atom instead of methyl group.
The lone pair of the N interacts with the π(pi) system of the ring and is less available
To displace the –cl ion. As a result the intermediate Aziridinium ionis less easily
Formed and strong neucleophiles such as guanine with react with it.
Melphalan takes advantage of this type of property.
The drug can be given orally and also it mimic the amino acid mooiety
Phenylalanine. As a result this drug is more likely to be recognized as an
Amino acid and taken in to cells by carrier proteins.

33. Chlorambucil
Uses: Multiple myeloma, Lymphosarcoma,Lymphocytic leukemia, Polycythemiavera
Overian adenocarcinoma, Hodkin’s disease and in combination testicular cancer.
Chlorambucil acts by cross linking of DNA which results in formation of altered proteins leading to decrease
in cell division that ultimately causes death of the cell.

34. Busulphan
Busulphan is a cytotoxic drug belonging to the group of alklating agent. It
Is chemically, dimethane sulphonate derivative.Similar to chlorambucil.
Mechanism of action:
Busulphan is a bifunctional alkylating agent. In alkylation the sulphonate groups are good leaving groups
and play a similar role to the Chlorines in the nitrogen mustards..
Cross-linking with busulfan
Sulfonate groups are good leaving groups

35. Synthesis of busulphan

36. Nitrasoureas:
Carmustine
Carmustine and lomustine are examples of
chloroethylnitrasoureas
Which are lipid soluble and can cross the
blood-brain barrier. As a result they have
been used in the treatment of brain
tumours and
Menengeal leukaemia.
The drug decomposes spontaneously in the body to
form 2 active compounds ----an alkylating
agent and a Carbamoylating agent.
The organic isocyanate which is formed
carbamoylates lysine residues in proteins and
may inactive DNA repair enzymes.
The alkylating agent reacts initially with the O-6
position of a guanine moiety in one strand of
DNA, then with the O-6 position of a guanine
unit or the N-3 position of cytosine in the other
strand to produce interstrand cross-linking.
Nitrosoureas have dual mechanisms of
Action where by they alkylate DNA and
Carbamoylate proteins.

37. Synthesis of carmustine
(formic acid)

38. • Physico-chemical properties:
white powder, slight odour. PH =5 to 6.0.
M.P=27-300
C, poorly soluble in water, freely soluble
in ethanol.
Toxic effects: nausea, vomiting, abdominal pain,
flushing, fever, chills, changes in vision,
Chest pain, yellowing of skin or eyes, headache.
Therapeutic uses: Brain tumours, Multiple
Myloma, Hodgkin’s disease, Gastrointestinal,lung and
colon cancer when other treatment has failed.
Carmustine is given I.V because of its rapid
metabolized. Lomustine can be given orally.

39. Procarbazine
• Procarbazine is an antineoplastic agent belonging to the class of alkylating agent.
• Chemically it is a derivative of methyl hydrazine.
Mechanism/mode of action:
Procarbazine exerts its cytotoxic action by Converting into highly reactive alkylating
species azoprocarbazine which causes 0066
-methylation-methylation of guanine nucleotide
particularly thymine. This results in mispairs that Encourages point mutations
during replication cycles of DNA. Subsequently normal postreplication mismatch
Repair (MMR) systems gets activated and leads to the destruction of the cells.
Physico-chemical properties:
Solid , slight odour,white to paleyellow colour, M.P= 2230
C Very soluble in water
Soluble in methanol and ethanol.
Adverse/toxic effects:
Nausea, vlomiting, constipation,drymouth,drowsiness,dizziness, muscle twitching,
Weakness and temporary hair loss. Severe chest pain, seizures,irregular heart bea
Mental changes, blood in urine or stools. Yellowing of eyes or skin.
Therapeutic
usesHodgkin’s lymphoma., It is also used for certain brain tumours, small-cell carcinomas
Of the lung, Non –Hodgkin’s lymphomas, and malignant melanoma.

40. • Procarbazine is a prodrug and thought to undergo oxidation by cytochrome P450 enzymes
(ACTIVATED BY THE ENZYMES) to produce the methyl diazonium ion. This is alkylating agent .
Reaction of this ion with RNA or DNA results in methylation mainly at the 06
-position of
guanine. DNA fragmentation can also occur.
N = N+
– CH3 ----------- N2 + +
CH3
--
Synthesis
Methyl diazonium ion
condensation
Alkaline hydrolysis

41. ANTIMETABOLITES
• Antimetabolites are agents which inhibit the enzymes
involved in the synthesis of DNA or its nucleotide building
blocks. This is the another method of disrupting DNA
function.
• The inhibitors involved are described as antimetabolites.
Genarally the cellular components like folic acid, purines and pyrimidines
that are Involved in the synthesis of Nuclic acids (DNA,RNA)
Antimetabolites inhibit nuclic acid synthesis by Competitive inhibition of
cellular components.
They achieve this by combining with specific enzyme or getting incorporated
into the specific enzyme thereby
Forming inactive macromolecules and consequent cell death. They act
Specific phase of the cell cycle.

42. 5-fluorouracil
• It is an anticancer drug used for the treatment of breast,liver,
skin cancer which inhibit enzyme directly.
• 5-flurouracil is an antineoplastic agent belonging to the class
of antimetabolites i.e. pyrimidine antagonist.
• It is a prodrug which is converted in the
body it its active form- deoxyribonucleotide that exerts the
cytotoxic effect by inhibiting the normal pyrimidine formation
which results in the inhibition of synthesis of DNA.

43. (deoxy thymidine monophosphate
.
.
Here things start to
To go wrong further reaction
is impossible.
.
Fluorine atom is there instead of hydrogen
As a result flurouracil skeleton remains covalently
Irreversibly bound to the active site. Now thymidine synthesis terminated .

44. synthesisSynthesis of 5-
flurouracil
Fluoroxy trifluoro methane
It is a solid, white, odourless, partially soluble in water,methanol, insoluble in diehtyl ether
Having melting point 282o
C.
Adverse /Toxic effects:
Nausea, tiredness, diarrhoea, pigmentation of skin,mouth sores, anaemia.blurred vision
Loss of appetite, rashes, hair thinning , dermatitis.
Therapeutic uses
5-Flurouracil is used for treating the following cancers
Breast cancer
Liver
Skin cancer
Stomach, pancreatic cancer, colon and rectal cancer.
Cancer of anus, bladder, cervix, endometrium, prostrate, ovaries, penis.
5-

45. 6-Mercaptopurine.
6-Mercaptopurine is an anticancer
drug belonging to antimetabolite
class. Chemically it is a purine 6-
thiol.
Mechanism of action
It is an analogue of naturally
occurring purine, which is
essential component of DNA
called adenine. After the
intercellular conversion of
mecaptopurine to active
nucleosides, it gets interfered
with nucleic acid synthesis.
Both these agents converts in to a common product
thio-GMP and next converts to thio- dGTP
before incorporation into
RNA and DNA
respectively.

46. Synthesis
.
Therapeutic uses:
It exhibits immunosuppressant action.
This drug is used in the primarily for the treatment of acute leukaemias and more effective
In children than adults.
Chorio carcinoma, chronic myelocytic leukeia, Non hodkin’s lymphoma, psoriatic arthritis,
Polycythemia vera, Ulcerative colitis and chrohn’s disease.
Dose: it is given orally at a dose of 2.5mg/kg body weight or 75 to 100 mg/sq.m BSA.

47. MethotrexateMethotrexate is one of the most widely used Antimetabolites in cancer chemotherapy.
Mechanism of action: Methotrexate is an antagonist of folic acid.
The DHFR is an important enzyme required for the formation of THF from
DHF.
In the absence of THF, the cells cannot synthesize purine and thymidine
nucleotides which ultimately blocks the formation of DNA and RNA.
Without DNA the cell cannot replicate and ultimately dies. The binding of
methotrexate to DHFR is so tight that is termed as pseudoirreversible.
Dihydrofolate reductase
Dihydrofolic acid ------------------------------------------ Tetrahydrofolic acid.
Dihydrofolate reductase
Methotrexate ---------------------------------------------- No reaction.
In the cell folic acid is first of all reduced to FH2and then FH4.
Methotrexate is able to inhibit the enzyme dihydrofolate reductase and
does not allow the formation of tetrahydrofolate which has been
essential for the synthesis of purine and pyrimidine and there by check
the Formation of DNA and RNA.

48. Synthesis:

49. • Physico-chemical properties:
It occurs as yellow to orange brown crystalline powder.It is insoluble in water
Freely soluble in dilute solution of alkali and slightly soluble in dil.Hcl . M.P=1920
c.
Adverse effects:
Depression of bone marrow which lead to
Leucopenia,thrombocytopenia and anaemias.
In low doses methotrexate is given repeatedly causes megaloblastic anaemia
and high doses produce pancytopenia.
Uses:
It provedes great benefit to patients suffering with
Chronic carcinima, the acute leukemias,osteosarcoma, and head, neck and breast
cancer.
Lung cancer.
Acute lymphocytic leukemia and acute myelocytic leukaemia.
Poriasis.
Autoimmune diseases like dermatomyositis and rhuematoid arthritis.
Dose: 30mg/sq.m BSA weekly in 2 divided doses for acute leukaemia.
For chronic carcinomas it is given as 15-30mg/day orally for 5 days.

50. Vinka alkaloids
Vinblastine is a clinically useful vinka alkaloid. It is derived form the Madagascar periwinkle
plant (catharanthus roseus) formerly known as Vinka rosea.
The alkaloid vinblastine is made up of two
Moieties namely catharanthine and vindoline
Mechanism of action:
Vinblastine shows its action by binding to tubulin to prevent it from
polymerizing into microtubules. Thus the drug prevents it
polymerization in microtubules. This leads to inhibition of mitotic
spindle formation by arresting the mitosis at metaphase. Thus the
cell division does not occur.
Physicochemical properties:
It is white to slightly yellow crystalline odourless powder soluble in water, methanol,
ethanol, chloroform and insoluble in ether having M.P=285o
C.
Toxic effects:
Nausea, vomiting and muscle plain, lower back pain, joint pain ,temporary hair loss, painful
urination, blood in urine or stools, dizziness, double vision may also occur, allergic
reactions include rash, itching ,swelling and difficulty in breathing.

51. Structure of vinblastine
Chemically
it is a complex structure consisting of two polycyclic units i.e.
Catharathine and vindoline.

52. SAR:
The presence of acetyl group is very essential for vinblastine to exhibit it
Anti cancer activity. When this is hydrolysed activity gets destroyed.
2. When free hydroxyl grops were acetylated the drug lost its
Antimalignant activity.
3.The potency of vinblastine reduces drastically when the double bonds
were initially hydrogenated and finally converted to carbinol group via
reduction.

53. Uses of vinblastine:
1.Vinblastine has been used in combination
Therapies for the treatment of lymphomas,
Testicular cancer and ovarian cancer.
Hodgkin’s disease.
Non-Hodgkin’s lymphoma
Kaposi’s sarcoma
Mycosis fungoides.
Dose: It is administered 0.3mg/kg for 3 weeks by I.V
infusion.

54. Vincristine:
Vincristine is also obtained from Catharanthus roseus,
(vinca rosea)
Chemically it consists of 2 polycyclic units.
It is made up of 2 moieties namely catharanthine and
vindoline.
It binds to the tubulin and has greater affinity towards
tubulin than the vinblastine.
It is mainly used in combination therapy to treat
Acute leukaemias, Hodgkin’s lymphoma, small cell
Lung carcinoma and a variety of other tumoues.

55. Mechanisam of vincristine:
Tubulin is a structural protein which is
crucial to cell division.
Genarally when the cell is about to
divide
Its microtubules depolymerize to give
tubulin.
The tubulin is then repolymerized to
form Structure called a spindle
which then serves to push apart
the two new cells and to act as a
frame work on which the
chromosome of the original cell
are transferred to the nuclei of the
daughter cells.
Vincristine shows its action by binding to tubulin to prevent it
from polymerizing into microtubules.

56. Physicochemical properties:
It is white to yellow, crystalline,odourless,
Freely soluble in water insoluble in ether and having M.P=220
C.
Adverse effects:
Loss of sleep, tendon reflexes, severe peripheral neuropathy, some time in severe cases loss of
motor function, foot drop, ataxia, bone marrow suppression( it is less common than
vinblastine), constipation, urinary disturbances and alopecia.
Vincristine is used combination therapy toVincristine is used combination therapy to
treat acute leukaemias, Hodgkin’s lymphoma, small cell lung cancer.treat acute leukaemias, Hodgkin’s lymphoma, small cell lung cancer.
Burkitt’s lymphomaBurkitt’s lymphoma
Wilm’s tumourWilm’s tumour
Myeloma and neuroblastomaMyeloma and neuroblastoma
Kaposi’s sarcomaKaposi’s sarcoma
RhabdomyosarcomaRhabdomyosarcoma
Brain, lung, breast and head and neck tumours.Brain, lung, breast and head and neck tumours.
Therapeutic uses:

57. • The sulfur mustards, of which mustard gas (1,5-dichloro-3-
thiapentane) is a member, are a class of related cytotoxic,
vesicant chemical warfare agents with the ability to form
large blisters on exposed skin. Pure sulfur mustards are
colorless, viscous liquids at room temperature. However,
when used in impure form as warfare agents they are
usually yellow-brown in color and have an odor resembling
mustard plants, garlic or horseradish, hence the name
Mustard agents can be deployed on the battlefield via
spraying from aircraft, or more typically by means of air-
dropped bombs or artillery shells. It has proved effective
against entrenched troops and encampments. Without
proper protection, mustard gas can be proved to be lethal to
infantry

58. Sulfur mustards and nitrogen mustards
Mechanism of toxicityMechanism of toxicity
The compound readily eliminates aThe compound readily eliminates a chloridechloride
ion by intramolecularion by intramolecular nucleophilic substitutionnucleophilic substitution
to form a cyclicto form a cyclic sulfoniumsulfonium ion. This veryion. This very
reactive intermediate tends to bond to thereactive intermediate tends to bond to the
guanine nucleotide in DNA strands, which isguanine nucleotide in DNA strands, which is
particularly detrimental to cellular health.Thisparticularly detrimental to cellular health.This
alkylation can lead to cellular death andalkylation can lead to cellular death and
cancer .Mustard gas is not very soluble incancer .Mustard gas is not very soluble in
water but is very soluble in fat, contributing towater but is very soluble in fat, contributing to
its rapid absorption into the skinits rapid absorption into the skin

60. Soldier with muster gas burns to his back

61. Mustard gas
• The most widely reported and, perhaps, the
most effective gas of the First World War was
mustard gas, a vesicant, which was introduced
by Germany in July 1917 prior to the Third
Battle of Ypres.[4] The Germans marked their
shells yellow for mustard gas and green for
chlorine and phosgene, so they called the new
gas Yellow Cross Mustard gas is not a
particularly effective killing agent (though in
high enough doses it is fatal) but can be used
to harass and disable the enemy and pollute
the battlefield. Delivered in artillery shells,
mustard gas was heavier than air, and it
settled to the ground as an oily liquid
resembling sherry. Once in the soil, mustard
gas remained active for several days, weeks, or
even months, depending on the weather
conditions.[32]
• The skin of victims of mustard gas blistered,
their eyes became very sore and they began to
vomit. Mustard gas caused internal and
external bleeding and attacked the bronchial
tubes, stripping off the mucous membrane.
This was extremely painful and most soldiers
had to be strapped to their beds. It usually
took a person four or five weeks to die of
mustard gas exposureMustard gas was the
agent of choice, with the British stockpiling
40,719 tons, the Russians 77,400 tons, the
Americans over 87,000 tons and the Germans
27,597 tons.[38]

63. Poison gas attack using gas cylenders in
world war -1

64. ALTERNATIVES FOR ANTINEOPLASTICS
Cancer chemotherapy is now entering a new era which can be
described as molecular targeted therapeutics-highly selective
agents which target specific molecular targets that are
abnormal or over expressed in the cancer cell.
Progress in this era has arisen from a better understanding of
the cellular chemistry involved in particular cancer cells
The development of kinase inhibitors such as IMATINIB(glivec) is
a much heralded illustration of this approach
The use of antibodies and gene therapy is another area of
research which shows huge potential.

65. Finally, one of the best ways of reducing
cancer is …..
• Firstly…Public education campaigns are important in highlighting the
dangers of smoking, because possibly as many as 30% of cancers are
caused by smoking, excessive drinking, and hazardous solvents, as well
as promoting healthy diets and lifestyles.
• Secondly, another 30% of cancers are diet related that’s why everybody
should take healthy diets and lifestyles.
• The benefits of eating high-fibre foods, fruit, and vegetables are clear.
• Infact, there have been various research projects aimed at identifying
the specific chemicals in these foods which are responsible for this
protective property. For example,
• Dithiolthiones are a group of chemicals in broccoli, cauliflower, and
cabbage which appear to have protective properties, one of which
involves the activation of enzymes in the liver to detoxify carcinogens.
• Genistein is a protective compound found in soy products used
commonly in Asian populations have a low incidence of breast, prostate,
colon cancers.
• Epigallocatechin gallate, an antioxidant present in green tea, is another
potential protective agent.
• Synthetic drugs are also being investigated as possible cancer
preventives
(finasteride, aspirin, ibuprofen, and difluoromethylornithine).

67. Campaign Goals
• Increase Awareness
• Increase Screening
• Reduce Incidence
• Reduce Mortality
• Reduce Burden
• Improve Quality of Life

68. Prevention
You can reduce the risk of getting a cancerous (malignant) tumor by:
Eating a healthy diet
Exercising regularly
Limiting alcohol
Maintaining a healthy weight
Minimizing your exposure to radiation and toxic chemicals
Not smoking or chewing tobacco
Reducing sun exposure, especially if you burn easily
Cancer screenings, such as mammography and breast examination for breast
cancer and colonoscopy for colon cancer, may help catch these cancers at
their early stages when they are most treatable.
Some people at high risk for developing certain cancers can take medication
to reduce their risk.

69. Smokers who smoke between 1 and 14 cigarettes a day have eight times the risk of
dying from lung cancer compared to non-smokers. Smokers who smoke more than 25
cigarettes a day have 25 times this risk compared to non-smokers
facts
You can see how the lung looks
without the effects of inhalation of
smoke.
Note black specks throughout
indicative of carbon deposits from
pollution.
Smokers lung with cancer. White area
on top is the cancer, this is what killed
the person. The blackened area is just
the deposit of tars that all smokers
paint into their lungs with every puff
they take.

70. Foye’s Principles Of Medicinal Chemistry 6th
Edition By Thomas L Lemke/ David A
Williams.
Wilson And Gisvold’s Text Book Of Organic Medicinal And Pharmaceutical Chemistry
11th
Edition.
Medicinal Chemistry- By Alka.L.Gupta.
Essentials Of Medicinal Chemistry-2nd
Edition By Andrejus Korolkovas.
An Introduction To Medicinal Chemistry-3rd
Edition By Grahaml.Patrick.
Organic Pharmaceutical Chemistry And Medicinal Chemistry. Vol 3 By J.S Qadry , S.S
Qadry And Rajendra Singh.
Quintessence Of Medical Pharmacology By Sujit K. Chaudari.
Medicinal Chemisty. Ramarao Nadendla.
A Text Book Of Medicinal Chemistry Vol2 Surendra. N Pandeya.
Moscow JA, Cowan KH. Biology of cancer. In: Goldman L, Ausiello D, eds. Cecil
Medicine. 23rd ed. Philadelphia, Pa: Saunders Elsevier;2007:chap 187.
Thun MJ. Epidemiology of cancer. In: Goldman L, Ausiello D, eds. Cecil Medicine. 23rd
ed. Philadelphia, Pa: Saunders Elsevier;2007:chap 185.
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