SAR and Mechanism of Anticancer agents

1. ANTICANCER AGENTS
DR. MANJOOR AHAMAD SYED,
M.Pharm, Ph.D
Associate. Professor
Department of Medicinal Chemistry,
College of Public Health and Medical Sciences,
Mettu University, Mettu
Post Box No-318
Ethiopia.

2. ANTICANCER AGENTS
The drugs which are used in the treatment of cancer are known as Antineoplastic or
anticancer agents. Antineoplastic agents are also known as cytotoxic agents.
Cancer is a very difficult disease to treat since lack of reliable diagnostic tests for the early
detection and not having the compounds which will cure any form of cancer.
INTRODUCTION TO CANCER
Cancer is a term used for disease in which abnormal cell divide without control and are able
to invade other tissues. Cancer cells can spread to other parts of the body through the blood
and lymph system.
The medical term for tumor or cancer is Neoplasm, the 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”

3. TYPES OF TUMORS: Not all tumors are cancerous, tumors can be benign or malignant
Benign tumors: They are not cancerous. They can often be removed, and in most cases, they
do not come back. Cells in benign tumor do not spread to other parts of the body.
Malignant tumors: They are cancerous. Cells in these tumors can invade nearby tissues and
spread to other parts of the body. The spread of cancer from one part of the body to another is
called metastasis.

5. 303 pound ovarian tumour

6. CAUSES OF CANCER
1. Physical agents
2. Biological agents
a. Bacterial agents: peptic ulcers and chronic gastritis when left untreated for a long time
leads to gastric cancer.
b. Fungal agents: Aspergillus flavus releases aflatoxin in stored food and grains, if this
contaminated food is consumed (especially by Hepatitis B virus infected patients) it leads
to hepatocellular carcinoma.
c. Viral agents: Cervical cancer, Burkett’s lymphoma, hairy cell leukemia and Hepatic
carcinoma.
3. Chemical agents
4. Genetic factors

7. CAUSES OF CANCER
5. Diet and habits
6. Hormones and Drugs
7. Epidemiological factors
a. Geographical and racial factors: Climate, soil, diet habit and customs etc.
b. Environmental and cultural factors: Exposure to industrial contaminants, smoke,
radioactive metals.
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.

8. TREATMENT OF CANCER
Cancer ca be treated by following means.
1. Surgery: Robotic radical prostatectomy for prostate cancer.
2. Radiation therapy: In combination with other therapies iodine-131 (Thyroid cancer),
Iridium-192 (Breast cancer)
3. Immunotherapy: Immune system made strong to fight cancer
4. Hormonal therapy: Killing cancer cells by altering hormone level.
5. Gene therapy: By replacing defective genes
6. Chemotherapy: Chemotherapy is the term applied for a wide range of chemical substances
i.e. drugs that are employed in the treatment of cancer. These drugs may act by various
mechanisms like interfering with the replication of DNA or inhibiting the formation of
important molecules which are needed for DNA formation and inhibiting the mitotic spindle.

9. CLASSIFICATION OF ANTICANCER DRUGS
1. ALKYLATING AGENTS
a. Nitrogen Mustard: Mechlorethamine,
Cyclophosphamide, Melphalan and
Chlorambucil
b. Nitrosoureas: Carmustine, Lomustine
and semustine
c. Alkyl sulphonstes: Busulfan
d. Triazines: Dacarbazine, Procarbazine
e. Ethylenimine: Thiotepa
The anticancer drugs are chemically classified in to different types.
2. ANTIMETABOLITES
a. Folate antagonists: Methotrexate
b. Purine antagonists: 6-Mercaptopurine,
6-Thioguanine and Azathioprine.
c. Pyrimidineantagonists: 5-Fluorouracil,
Cytarbine
3. ANTIBIOTICS
Actinomycin-D, Doxorubicin,
Daunorubucin, Blemycin, Mitomycin C,
Mithramycin (plicamycin)

10. 4. IMMUNOMODULATORS
a. Levamisole
b. Interferon: Interferon α-2a and 2b
c. Interleukins: Aldesleukin
5. PLANT DERIVED PRODUCTS
a. Vinca alkaloids: Vincristine,
Vinblastine
b. Axanes: Paclitaxel, Docetaxel
c. Epidophyllo toxin: Etoposide,
Teniposide
6. HORMONES AND HORMONE
ANTAGONISTS
a. Glucocorticoids: Prednisolone, Prednisone
b. Estrogen: Diethylstilbestrol
c. Anti-Estrogen: Tamoxifen
d. Androgens and antiandrogens:
Testosterone, Flutamide
e. Progestin: Medroxyprogesterone acetate

11. 7. MONOCLONALANTIBODIES
Trastuzumab, Rituximab, Imatinib
8. RADIOISOTOPES
Radio iodine - I131, Radiophosphorous - P32
9. MISCELLANEOUS DRUGS
Hydroxy urea, Mitotane, Cisplatin, Carboplatin, Mitoxantrone, L- Asparginase.

13. ALKYLATING AGENTS:
These are the compounds that are capable of introducing an alkyl group in to nucleophilic sites
on DNA, RNA or any enzyme through covalent bond. These agents are thought to react with
the 7th 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 strand and prevents mitosis.
The favored site on DNA is at N7 position of Guanine, Adenine, Cytosine and even the sugar
phosphate groups.

14. Nitrogen Mustard: Mechlorethamine, Cyclophosphamide, Melphalan and Chlorambucil
CH2CH2CH2COOH
N
ClH 2CH2C
ClH 2CH2C
4-{4-[bis(2-chloroethyl)amino]phenyl}butanoic acid
CH2CH2CH2COOH
N
H2
4-(4-aminophenyl)butanoic acid
O
1.
2. SOCl 2
CH2CH2CH2COOH
N
ClH 2CH2C
ClH 2CH2C
Chlorambucil
CHLORAMBUCIL
Synthesis:
Adverse Effects:
Bone marrow suppression. This means you'll have fewer red and white blood cells and platelets.
Symptoms can include: Mouth irritation or sores, Nausea, Vomiting, Diarrhea.
USES:
Chlorambucil is used treat a certain type of chronic lymphocytic leukemia (CLL; a type of
cancer of the white blood cells). Chlorambucil is also used to treat non-Hodgkin's lymphoma
(NHL) and Hodgkin's disease (types of cancer that begin in certain white blood cells that
normally fight infection).

15. P
N
H
O
O
N
CH2CH2Cl
CH2CH2Cl
N,N-bis(2-chloroethyl)-1,3,2-oxazaphosphinan-2-amine 2-oxide
P
Cl
Cl
O
N
CH2CH2Cl
CH2CH2Cl
+ N
H2 OH
Dioxane
-2HCl
P
N
H
O
O
N
CH2CH2Cl
CH2CH2Cl
Cyclophosphamide
bis(2-chloroethyl)phosphoramidic dichloride
3-aminopropan-1-ol
CYCLOPHOSPHAMIDE:
Synthesis:
Adverse Effects:
Nausea, vomiting, loss of appetite or weight, abdominal pain, diarrhea, hair loss, sores on the
mouth or tongue, changes in skin color.
USES:
Cyclophosphamide is in a class of medications called alkylating agents. When
cyclophosphamide is used to treat cancer, it works by slowing or stopping the growth
of cancer cells in your body. When cyclophosphamide is used to treat nephrotic syndrome, it
works by suppressing your body's immune system.

16. MECHLORETHAMINE HCl
N
CH2CH2Cl
CH2CH2Cl
. HCl
2,2 - dichloro-N-methyl diethylamine HCl
Adverse Effects:
These side effects are less common side effects (occurring in about 10-29%) of patients
receiving Mechlorethamine:
Fever, Diarrhea, Poor appetite, Taste changes (metallic taste), Ringing in the ears (tinnitus) (see
hearing problems), Abnormal blood tests: increased uric acid levels.
USES:
Mechlorethamine is used to treat Hodgkin's lymphoma (Hodgkin's disease) and certain types of
non-Hodgkin's lymphoma (types of cancer that begin in a type of white blood cells that
normally fights infection); mycosis fungoides (a type of cancer of the immune system that first
appear as skin rashes)

17. MELPHALAN
N
ClH2CH2C
ClH2CH2C
CH2
NH2
COOH
2-amino-3-{4-[bis(2-chloroethyl)amino]phenyl}propanoic acid
Adverse Effects:
Side effects of Alkeran include:
weight loss, loss of appetite, weakness, blistering skin or acne, nausea, vomiting, diarrhea,
white patches or sores inside your mouth or on your lips.
USES:
Melphalan is used to treat multiple myeloma (a type of cancer of the bone marrow).
Melphalan is also used to treat a certain type of ovarian cancer (cancer that begins in the
female reproductive organs where eggs are formed). Melphalan is in a class of medications
called alkylating agents.

18. H3C
S
O
O
S
CH3
O
O
O
O
1,4-butanediol-dimethyl sulfonate
2 CH 3SO2Cl + O
H
OH
Pyridine
- 2 HCl H3C
S
O
O
S
CH3
O
O
O
O
Busulfan
butane-1,4-diol
Methane sulfonyl chloride
BUSULFAN
Synthesis:
Adverse Effects:
Nausea, diarrhea, loss of appetite or weight, constipation, sores in the mouth and throat,
dry mouth, headache, difficulty falling asleep or staying asleep.
Uses:
Busulfan is used treat a certain type of chronic myelogenous leukemia (CML; a type of
cancer of the white blood cells). Busulfan is in a class of medications called alkylating
agents. It works by slowing or stopping the growth of cancer cells in your body.

19. PROCARBAZINE
Mechanism of Action:
Procarbazine is cell-phase specific for the S phase of cell division. The precise mode of
cytotoxic action of procarbazine has not been clearly defined. There is evidence that the drug
may act by inhibition of protein, RNA and DNA synthesis.
Adverse Effects:
Hair loss, Mouth sores, Diarrhea, Constipation, Flu-like symptoms (fever, chills, generalized
aches and pains), Central neurotoxicity: weakness, loss of balance, headache, unsteadiness,
drowsiness or dizziness.
USES:
This medication is used to treat Hodgkin's disease (also known as Hodgkin's lymphoma).
Procarbazine belongs to a class of drugs known as alkylating agents. It works by slowing or
stopping the growth of cancer cells.

20. N P N
N
S
1,1',1''-phosphorothioyltriaziridine
NH + PSCl 3
aziridine
Trichlorophosphine sulfide
(C2H5)3N
5 -10
0
C / NaOH
N P N
N
S
Thiotepa
THIOTEPA
Synthesis:
Adverse Effects:
Fatigue, weakness, nausea, vomiting, stomach pain, loss of appetite, redness or inflammation
of the eyes, puffy eyelids.
USES:
Thiotepa is used to treat cancer. It works by slowing or stopping the growth of cancer cells.
Thiotepa is often given into the bladder to treat bladder cancer. Thiotepa is also used with
other medications to prevent rejection of a stem cell transplant.

21. CARMUSTINE
Adverse Effects:
Nausea and vomiting, usually within 2-4
hours of infusion, lasting for about 4-6
hours, Facial flushing (see skin problems),
Pain and burning at the injection site, Low
blood counts.
USES:
This medication is used to treat certain
types of cancer (including multiple
myeloma, brain tumor, Hodgkin's disease,
non-Hodgkin's lymphoma).
1,3- Bis (2- chloroethyl)- 1- nitrosourea
LOMUSTINE:
Adverse Effects:
Low blood counts (bone marrow suppression).
Your white and red blood cells and platelets may
temporarily decrease, Nausea and vomiting.
Usually within 3-6 hours of taking medication.
USES:
Lomustine is used to treat certain types of brain
tumors. Lomustine is also used with other
medications to treat Hodgkin's lymphoma
(Hodgkin's disease) that has not improved or that
has worsened after treatment with other
medications.
(1 - (2 - chloroethyl)-3- cyclohexyl -1- nitrosourea)

22. ANTIMETABOLITES
Antimetabolite drugs which inhibit the enzymes involved in the synthesis of DNA or its nucleotide
building blocks. Generally, the cellular components like Folic acid, purines and pyrimidines that are
involved in the synthesis of nucleic acids (DNA, RNA).
N
H
N
H
O
O
F
5 - Fluoro uracil
CF3OF
Fluoroxy trifluoro methane
N
H
N
H
O
O Fluorination
N
H
N
H
O
O
F
Uracil
5 - Fluoro uracil
5 – FLUOROURACIL
Synthesis:
Adverse Effects:
Diarrhea, Nausea and possible occasional
vomiting, Mouth sores, Poor appetite, Watery eyes,
sensitivity to light (photophobia), Taste changes,
metallic taste in mouth during infusion.
USES:
Fluorouracil (5-FU), sold under the brand name
Adrucil among others, is a medication used to treat
cancer. By injection into a vein it is used for colon
cancer, esophageal cancer, stomach cancer,
pancreatic cancer, breast cancer, and cervical
cancer.

23. Mechanism of action:
5-FU acts in several ways, but principally as a thymidylate synthase (TS) inhibitor. Interrupting
the action of this enzyme blocks synthesis of the pyrimidine thymidine, which is a nucleoside
required for DNA replication.

24. 6 – MERCAPTOPURINE
N
N
N
N
H
S
H
6- mercaptopurine
N
N
N
N
H
OH
Hypoxanthine
+
Phosphorus pentasulphide
P2S5
N
N
N
N
H
S
H
6- mercaptopurine
Synthesis:
Adverse Effects:
Black, tarry stools, clay colored stools, decreased appetite, fever or chills, nausea, vomiting, rash, itchy
skin, stomach pain or tenderness, swelling of the feet or lower legs.
USES:
Mercaptopurine (6-MP), sold under the brand name Purinethol among others, is a medication used for
cancer and autoimmune diseases. Specifically it is used to treat acute lymphocytic leukemia (ALL),
chronic myeloid leukemia (CML), Crohn's disease, and ulcerative colitis.

25. Mechanism of Action:
6-MP ribonucleotide inhibits purine nucleotide synthesis and metabolism by inhibiting an enzyme
called phosphoribosyl pyrophosphate amidotransferase (PRPP amidotransferase) to inhibit the action
of HPRT (Hypoxanthine Phospho Ribosyl Transferase). Since this enzyme is the rate limiting factor for
purine synthesis, this alters the synthesis and function of RNA and DNA.

26. N
N
N
N
H
SH
N
H2
2-amino-9H-purine-6-thiol
N
N
H
N
N
H
O
N
H2
1. P2S5
2. NH 4OH
Pyridine
N
N
N
N
H
SH
N
H2
Guanine Thioguanine
THIOGUANINE
Synthesis:
Mechanism of action
Thioguanine is an antimetabolite as it is a
guanine analog and disrupts the synthesis of
DNA and RNA. 6-Thioguanine is an analog of
the purine guanine and is converted to 6-
thioguanosine monophosphate by the enzyme
hypoxanthine-guanine phosphoribosyl
transferase.
USES:
Thioguanine is used to treat acute myeloid leukemia (AML; a type of cancer that begins in the white
blood cells). Thioguanine is in a class of medications known as purine analogs. It works by slowing or
stopping the growth of cancer cells in your body.
Adverse Effects:
upset stomach, nausea, vomiting, diarrhea, hair
loss, itching or skin rash, or darkened skin color.

27. METHOTREXATE
N-[4-[[(2,4-diamino-6-ptridinyl)-
methyl] methylamino] benzoyl] glutamic
acid
USES:
Methotrexate is in a class of medications called antimetabolites. Methotrexate treats cancer by
slowing the growth of cancer cells. Methotrexate treats psoriasis by slowing the growth of skin cells
to stop scales from forming. Methotrexate may treat rheumatoid arthritis by decreasing the activity
of the immune system.
Adverse effects:
GI problems such as nausea and vomiting are the most
common side effects associated with methotrexate, affecting
between 20 and 65 percent of RA patients who take the drug.
Up to one third develop mouth ulcers or sores. Many also
complain of headaches, fatigue and an overall “blah” feeling.
Common side effects are like dizziness, drowsiness, headache,
swollen, tender gums, decreased appetite, reddened eyes, hair
loss.

28. Mechanism of action:
Methotrexate is an
antimetabolite of the
antifolate type. It is
thought to affect cancer
and rheumatoid arthritis
by two different
pathways. For cancer,
methotrexate
competitively inhibits
dihydrofolate reductase
(DHFR), an enzyme that
participates in the
tetrahydrofolate synthesis.

29. ANTIBIOTICS
O
O
O
H
O
R
1
O O
H
OH
O
R
4
H3C
CH3
R
2
R
3
NH2
Name of antibiotic R1 R2 R3 R4
Doxorubicin
(Adriamycin)
OCH3 H OH OH
Daunorubicin
(Rubidomycin)
OCH3 H OH H

30. DOXORUBICIN
Mechanism of action
Doxorubicin stabilizes the
topoisomerase II complex
after it has broken the
DNA chain for replication,
preventing the DNA
double helix from being
resealed and thereby
stopping the process of
replication.

31. Adverse Effects:
nausea and vomiting (may be severe), diarrhea, loss of appetite, missed menstrual periods, darkening
of your skin or nails, weakness, tiredness, eye redness.
USES:
Doxorubicin is used in combination with other medications to treat certain types of bladder, breast,
lung, stomach, and ovarian cancer; Hodgkin's lymphoma (Hodgkin's disease) and non-Hodgkin's
lymphoma (cancer that begins in the cells of the immune system); and certain types of leukemia
(cancer of the white blood cells

32. DAUNORUBICIN
Mechanism of action:
Daunorubicin is an anthracycline antibiotic which damages DNA by intercalating between base pairs
resulting in uncoiling of the helix, ultimately inhibiting DNA synthesis and DNA-dependent RNA
synthesis.
Adverse Effects:
mild nausea, vomiting, diarrhea, stomach pain, temporary hair loss, mild itching or rash or
red colored urine for 1 or 2 days following a dose.
USES:
Daunorubicin is also used with other chemotherapy drugs to treat a certain type of acute lymphocytic
leukemia (ALL; a type of cancer of the white blood cells). Daunorubicin is in a class of medications
called anthracyclines. It works by slowing or stopping the growth of cancer cells in your body.

33. BLEOMYCIN
Mechanism of action
Bleomycin acts by induction of DNA strand breaks. Some studies suggest bleomycin also inhibits
incorporation of thymidine into DNA strands. DNA cleavage by bleomycin depends on oxygen and
metal ions, at least in vitro.
Adverse Effects:
Fever and chills, Skin reactions: redness, darkening of the skin, stretch marks on the skin, skin
peeling, thickening of the skin, ulceration, Nail thickening, nail banding, Hair loss.
USES:
Used in the treatment of squamous cell cancers, melanoma, sarcoma, testicular and ovarian
cancer, Hodgkin's, and non-Hodgkin's lymphoma.
Also used to treat malignant pleural effusion (buildup of fluid in the space between the lining of
the lung and the chest wall).

34. ACTNOMYCIN – D
Mechanism of Action:
Dactinomycin is believed to produce its cytotoxic effects by binding DNA and inhibiting RNA
synthesis. Good evidence exists that this drug bind strongly, but reversibly, to DNA, interfering
with synthesis of RNA (prevention of RNA polymerase elongation) and, consequently, with
protein synthesis.
Adverse Effects:
Low white blood cell levels – increases risk of infection, Low red blood cell levels- increases risk
of anemia, Low platelet levels – increased risk of bleeding, Nausea and vomiting, Sores in the
mouth, Hair loss, Diarrhea.
USES:
Dactinomycin, also known as actinomycin D, is a chemotherapy medication used to treat a
number of types of cancer. This includes Wilms tumor, rhabdomyosarcoma, Ewing's sarcoma,
trophoblastic neoplasm, testicular cancer, and certain types of ovarian cancer. It is given by
injection into a vein.

35. MITOMYCIN
Mechanism of action:
Mitomycin is an alkylating agent with antineoplastic/ antibiotic properties. It binds to DNA during
DNA synthesis and causes inhibition of its synthesis and function. At higher concentrations, MMC
inhibits nucleotide synthesis which interferes with RNA transcription and protein synthesis.
Adverse Effects:
Acute Side Effects Due to MUTAMYCIN (mitomycin) were fever, anorexia, nausea, and vomiting.
They occurred in about 14% of 1,281 patients. Other: Headache, blurring of vision, confusion,
drowsiness, syncope, fatigue, edema, thrombophlebitis, hematemesis, diarrhea, and pain.
USES:
Mitomycin is used in combination with other medications to treat cancer of the stomach or pancreas
that has spread to other parts of the body and has not improved or worsened after treatment with
other medications, surgery, or radiation therapy.

36. LEVAMISOLE
(S)-6-Phenyl-2,3,5,6-tetrahydroimidazo[2,1-b][1,3]thiazole
Mechanism of action:
The mechanism of action of Levamisole as an anticancer drug in combination with fluorouracil is
unknown. The effects of levamisole on the immune system are complex. The drug appears to restore
depressed immune function rather than to stimulate response to above-normal levels.
Adverse effects:
Common adverse effects include nausea, abdominal pain, vomiting, diarrhea, metallic or altered taste,
flulike symptoms, mood elevation, insomnia, hyperalertness, dizziness, and headache. The most
serious adverse effect associated with levamisole is granulocytopenia.
USES:
It is approved for use in combination with the chemotherapy agent 5-fluorouracil in the treatment of
Duke's stage C colon cancer, following the surgical removal of the cancer.
Levamisole is an anthelminthic drug that was commonly
used for the treatment of parasitic, viral, and bacterial
infections. It was manufactured by Janssen and first used
in 1969 as an agent to treat worm infestations
Levamisole was approved by the FDA in 1990 as an
adjuvant treatment for colon cancer.

37. ALDESLEUKIN
Aldesleukin is a recombinant form of human interleukin-2, a cytokine that stimulates the
proliferation and maturation of T cells, which is used in immune therapy of renal cell cancer and
malignant melanoma.
USES:
Aldesleukin stimulates white blood cells including T cells and Natural Killer cells to kill melanoma
cells. Immunotherapy with monoclonal antibodies, such as nivolumab and ipilimumab, may help
sustain the body's immune system to attack the cancer.

38. PLANT PRODUCTS
Vinca alkaloids are a set of anti-mitotic and anti-microtubule alkaloid agents originally derived
from the periwinkle plant Catharanthus roseus (basionym Vinca rosea) and other vinca plants.
They block beta-tubulin polymerization in a dividing cell.
They have been used to treat diabetes, high blood pressure and have been used as disinfectants.
The vinca alkaloids are also important for being cancer fighters. There are four major vinca
alkaloids in clinical use: Vinblastine (VBL), vinorelbine (VRL), vincristine (VCR) and vindesine
(VDS).

39. Mechanism of Action of Vincristine and Vinblastine:
They work partly by binding to the tubulin protein, stopping the tubulin dimers from polymerizing to
form microtubules, causing the cell to be unable to separate its chromosomes during the metaphase.
The cell then undergoes apoptosis.

40. Common side effects of vincristine:
Include nausea, vomiting, weight loss, diarrhea, bloating, stomach/abdominal pain or cramps, mouth
sores, dizziness, headache, hair loss, constipation, loss of appetite, changes in sense of taste, and
numbness and tingling in the hands and feet.
Uses of Vincristine:
Cancers treated with Vincristine include: acute leukemia, Hodgkin's and non- Hodgkin's lymphoma,
neuroblastoma, rhabdomyosarcoma, Ewing's sarcoma, Wilms' tumor, multiple myeloma, chronic
leukemias, thyroid cancer, brain tumors. It is also used to treat some blood disorders.
Common side effects of vinblastine:
Low blood counts, white and red blood cells and platelets may temporarily decrease. This can put you at
increased risk for infection, anemia and/or bleeding, Injection site reactions, Fatigue, and weakness.
Uses of Vinblastine:
Vinblastine (VBL), sold under the brand name Velban among others, is a chemotherapy medication,
typically used with other medications, to treat a number of types of cancer. This includes Hodgkin's
lymphoma, non-small cell lung cancer, bladder cancer, brain cancer, melanoma, and testicular cancer.

41. TAXANES
Taxanes are a class of diterpenes. They were originally identified from plants of the genus Taxus
(yews), and feature a taxadiene core. Paclitaxel (Taxol) and docetaxel (Taxotere) are widely used
as chemotherapy agents. Cabazitaxel was FDA approved to treat hormone-refractory prostate
cancer.
TAXOL (Paclitaxel):
Mechanism of action:
Paclitaxel-treated cells have defects in mitotic spindle assembly, chromosome segregation, and cell division.
Unlike other tubulin-targeting drugs, such as colchicine, that inhibit microtubule assembly, paclitaxel stabilizes
the microtubule polymer and protects it from disassembly.
Adverse effects:
Low blood counts, Hair loss, Arthralgias and myalgias, pain in the joints and muscles, Peripheral neuropathy
(numbness and tingling of the hands and feet), Nausea and vomiting (usually mild)
Diarrhea, Mouth sores.
USES:
Taxol is used for the treatment of breast, ovarian, lung, bladder, prostate, melanoma, esophageal, as well as
other types of solid tumor cancers. It has also been used in Kaposi's sarcoma.

42. PREDNISOLONE
Mechanism of action:
Prednisone, or prednisolone, is a corticosteroid that presumably induces killing of
hematopoietic cancer cells through interaction with the glucocorticoid receptor and the induction of
apoptosis.
Adverse effects:
Increased appetite, weight gain, often in unexpected places such as the cheeks or the back of the
neck, mood swings, trouble sleeping, stomach upset or ulcers, osteoporosis (weaker bones)
higher blood pressure, higher blood sugar than normal.
Uses:
As treatment for a variety of cancers, such as leukemia, lymphoma, and multiple myeloma. To treat
nausea and vomiting associated with some chemotherapy drugs. Used to stimulate appetite in cancer
patients with severe appetite problems.

43. PREDNISONE
Mechanism of action:
Prednisone, or prednisolone, is a corticosteroid that presumably induces killing of hematopoietic
cancer cells through interaction with the glucocorticoid receptor262 and the induction of apoptosis.
Adverse effects:
increased appetite, weight gain, often in unexpected places such as the cheeks or the back of the neck,
mood swings, trouble sleeping, stomach upset or ulcers, osteoporosis (weaker bones)
higher blood pressure, higher blood sugar than normal.
Uses:
Prednisone is approved to be used to reduce inflammation and suppress (lower) the body's immune
response. It is used with other drugs to treat the following types of cancer: Acute lymphoblastic
leukemia (ALL) and acute myeloid leukemia (AML). It is used as palliative therapy in adults and
children.

44. DIETHYLSTILBESTROL
4,4'-[(3E)-Hex-3-ene-3,4-diyl]diphenol
Mechanism of action:
Diethylstilbestrol is a synthetic, nonsteroidal form of estrogen. A well-known teratogen and
carcinogen, diethylstilbestrol inhibits the hypothalamic-pituitary-gonadal axis, thereby blocking the
testicular synthesis of testosterone, lowering plasma testosterone, and inducing a chemical
castration.
Adverse effects:
Feeling sick, swollen feet and ankles and an increased risk of blood clots.
USES:
Diethylstilbestrol (DES) is a powerful synthetic estrogen. In the 1940s, it became the first hormonal
treatment shown to inhibit prostate cancer. Following this discovery, the accepted treatments for
advanced prostate cancer became orchiectomy and/or DES for the next two decades.

45. TAMOXIFEN
(Z)-2-[4-(1,2-Diphenylbut-1-enyl)phenoxy]-N,N-
dimethylethanamine
Mechanism of action:
The mechanism of action of tamoxifen is complex. Clearly, its principal mechanism of action is
mediated by its binding to the estrogen receptor and the blocking of the proliferative actions of
estrogen on mammary epithelium.
Adverse effects:
The most common side effects of tamoxifen are: increased tumor or bone pain. hot flashes.
nausea.
USES:
Tamoxifen is used to treat breast cancer. It is also used to reduce the chances of breast cancer in
high-risk patients. This medication can block the growth of breast cancer. It works by interfering
with the effects of estrogen in the breast tissue.

46. MEDROXYPROGESTERONE ACETATE
Mechanism of action:
The colony-formation of Ishikawa cells, which originate from well differentiated endometrial cancer,
and produce progestogen receptors (PR), was inhibited by high concentrations of
medroxyprogesterone acetate (MPA).
Adverse effect:
Feeling hot or flushed, a skin rash, itching, shivering, feeling dizzy, a headache, feeling breathless.
USES:
Medroxyprogesterone is a hormonal therapy drug used to treat breast, kidney and womb cancers. It
can be used for cancers that have started to spread to other parts of the body or have come back after
treatment. If you have a poor appetite, your doctor may prescribe medroxyprogesterone to increase
it.
Medroxyprogesterone acetate (MPA), also known as depot medroxyprogesterone
acetate (DMPA) in injectable form and sold under the brand name Depo-Provera
among others, is a hormonal medication of the progestin type. It is used as a method
of birth control and as a part of menopausal hormone therapy.

47. TRASTUZUMAB
Trastuzumab, sold under the brand name Herceptin among others, is a monoclonal antibody
used to treat breast cancer and stomach cancer. It is specifically used for cancer that is HER2
receptor positive. It may be used by itself or together with other chemotherapy medication.
USES:
Trastuzumab is used to treat metastatic (spread) breast cancer. It is effective against tumors that
overexpress the HER2/neu protein. As part of chemotherapy regimen for adjuvant treatment of
lymph-node positive, HER2/neu protein positive breast cancer.

48. CISPLATIN
Mechanism of action:
The mechanism of action of cisplatin has been associated with ability to crosslink with the urine
bases on the DNA to form DNA adducts, preventing repair of the DNA leading to DNA damage and
subsequently induces apoptosis within cancer cells.
Adverse effects:
Nausea and vomiting. Nausea may last up to 1 week after therapy, Low blood counts, Kidney
toxicity, Ototoxicity hearing loss, ringing in the ears, Blood test abnormalities (low magnesium, low
calcium, low potassium).
Uses:
Cisplatin is a chemotherapy medication used to treat a number of cancers. These include testicular
cancer, ovarian cancer, cervical cancer, breast cancer, bladder cancer, head and neck cancer,
esophageal cancer, lung cancer, mesothelioma, brain tumors and neuroblastoma. It is given by
injection into a vein.