anti cancer drug , medicinal chemistry , pharmacology ,

1. Anticancer drugs

2. INTRODUCTION
 Cancer occurs after normal cells have been
transformed into neoplastic cells through alteration of
their genetic material and the abnormal expression of
certain genes.
 Neoplastic cells usually exhibit chromosomal
abnormalities and the loss of their differentiated
properties.
 These changes lead to uncontrolled cell division and
many result in the invasion of previously unaffected
organs, a process called metastasis.

3. Carcinogens
• Ionising radiation – X Rays, UV light
• Chemicals – tar from cigarettes
• Virus infection – papilloma virus can be responsible
for cervical cancer.
• Hereditary predisposition – Some families are more
susceptible to getting certain cancers. Remember
you can’t inherit cancer its just that you maybe more
susceptible to getting it.

5. History of Cancer Treatment
• Long history of treating cancer, but did
not successfully begin until the invention
of the microscope
• Early 20th - surgery and radiation
• World Wars began chemical warfare, and
thus began chemotherapy - nitrogen
mustards
• Currently, targeted cancer therapy

6. CANCER INSTITUTES IN
TAMILNADU
• Adayar cancer institute, Chennai.
• Aringnar anna cancer hospital, karaikudi.
• CMC
• International cancer center, kanyakumari.
• Bernard institute of radiology and cancer
hospital, Chennai.
• Sri Ramakrishna institute of cancer.
• Chennai government hospital.

7. Recent techniques used in
Cancer treatment:
Recombinant DNA technology.
Newer experimental approaches
like isolated infusion approaches,
nano technology , electro
chemotherapy.

8. The Classification of Anticancer
Drugs
ANTICANCER
DRUGS
BASED ON
CHEMICAL
STRUCTURE
AND RESOURCE
BIOCHEMISTRY
&
MECHANISM OF
ACTION
BASED ON
CYCLE
OR
PHASE
SPECIFICITY

9. The Classification of Anticancer Drugs
BASED
ON
BIOCHEMISTRY
BLOCK
NUCLEIC ACID
BIOSYNTHESIS
BASED ON
STRUCTURE
&
FUNCTION
OF
DNA
INTERFERENCE
OF
TRANSCRIPTION
&
BLOCK RNA
SYNTHESIS
INTERFERENCE OF
PROTIEN SYNTHESIS
&
FUNCTION
OTHERS

10. The Classification of Anticancer Drugs
BASED
ON CYCLE OR
PHASE
SPECIFICITY
CELL CYCLE
NONSPECIFIC
AGENTS
ALKYLATING
AGENTS
PLATINUM
COMPOUNDS
ANTIBIOTICS
CELL CYCLE
SPECIFIC
AGENTS
S PHASE
EX:
ANTIMETABOLI
TES
M PHASE
EX:VINCA
ALKALOIDS
G2 PHASE
EX:BLEOMYCI
N

11. Block Nucleic Acid
(DNA, RNA)
Biosynthesis
Anti metabolites:
Folic Acid Antagonist: inhibit di hydro folate
reductase (metho trexate)
Pyrimidine Antagonist: inhibit thymidylate synthetase
(fluorouracil) ; inhibit DNA polymerase (cytarabine)
Purine Antagonist: inhibit interconversion of purine
nucleotide (mercaptopurine)
Ribonucleoside Diphosphate Reductase Antagonist:
(hydroxyl urea)

12. Interfere Transcription and Block RNA
Synthesis
Bind with DNA to block RNA
production.
Doxorubicin

13. Interfere
protein
synthesis
Anti tubulins
:Vinca alkaloids
and taxanes
Interfere the
function of
ribosomes:
harringtonines
Influence
aminoacid supply:
L-asparaginase

14. Influence the Structure and
Function of DNA
Alkylating Agent: Mechlorethamine, Cyclo
phosphamide and Thiotepa
Platinum: Cis-platinium
Antibiotic: Bleomycin and Mitomycin C
Topoismerase inhibitor: Camptothecine and
Podophyllotoxin

15. Anticancer Drugs
Alkylating agent
Antimetabolite
Antibiotics
• Alkaloid
• Hormones
• Others(Cis-platinum, carboplatin，
lobaplatin)

16. Alkylating Agents
 One of the frightening developments of World
War I was the introduction of chemical
warfare. These compounds were known as the
nitrogen mustard gases. The nitrogen mustards
were observed to inhibit cell growth,
especially of bone marrow. Shortly after the
war, these compounds were investigated and
shown to inhibit the growth of cancer cells.

17. MECHANISM OF
ACTION
Nitrogen mustards inhibit cell
reproduction by binding
irreversibly with the nucleic acids
(DNA). The specific type of
chemical bonding involved is
alkylation.

18. MECHANISM OF ACTION
• After alkylation, DNA is unable to replicate
and therefore can no longer synthesize proteins
and other essential cell metabolites.
• Consequently, cell reproduction is inhibited
and the cell eventually dies from the inability
to maintain its metabolic functions.

19. Classification of Alkylating
Agents
 Bis Chloroethyl Amines :
Cyclo phosphamide, Chlormethine,
Chlorambucil, Sarcolysine
 Nitrosoureas :
Carmustine,Lomustine
 Ethyleneammonium or Aziridines :
Thiotepa,triethylene melamine
 Alkylsulfonates : Busulfan

20. Cyclophosphamide
 Indications
 It is used in the treatment of chronic lymphocyctic
leukemia, breast and ovarian cancer, and a variety of other
cancers.
 It is also a potent immunosuppressant, it is used in the
management of rheumatoid disorders and autoimmune
nephritis.
 Adverse Effects:
 Alopecia, nausea, vomiting, myelosuppression, and
hemorrhagic cystitis.

21. Alkylating Agents—
Nitrosoureas
Carmustine, Lomustine, Semustine
Pharmacokinetics:
Nitrosoureas are highly lipophilic and reach
cerebrospinal fluid concentrations that are
about 30% of plasma concentrations.

22. Alkylating Agents—Thiotepa
Thiotepa is converted rapidly by liver
mixed-function oxidases to its active
metabolite triethylenephosphoramide
(TEPA); it is active in bladder cancer.
THIOTEPA
OXIDASES
TEPA

23. Classification of
Antimetabolites
 Folic acid Antagonists: MTX
 Purine Antagonists: 6MP
 Pyrimidine Antagonists:5FU,Cytarabine

24. Antimetabolites-Folic Acid Antagonist
Methotrexate (MTX)
Indications
The use of MTX in the treatment of choriocarinoma, a
trophoblastic tumour, was the first demonstration of
curative chemotherapy.
It is especially effective for treating acute lymphocytic
leukemia and for treating the meningeal metastasis of a
wide range of tumors.

25. FOLIC ACID-ANTA GONISTS
Methotrexate (MTX)
Adverse Effects
MTX is myelosuppressive, producing severe
leukopenia, bone marrow aplasia, and
thrombocytopenia.
This agent may produce severe git disturbances.
Renal toxicity may occur because of
precipitation (crystalluria) of the 7-OH
metabolite of MTX.

26. Antibiotics
Classification of Antibiotics:
Adriamycin
Bleomycin
Actinomycin D

27. Antibiotics
Adriamycin and Daunorubicin
Properties:
Adriamycin and Daunorubicin are tetracycline
rings with the sugar daunosamine. They are DNA
intercalating agents that block the synthesis of
DNA and RNA.
These agents are primarily toxic during the S
phase of cell cycle.
These agents imparts a red tinge to the urine.
Adramycin is used to treat acute leukemias,
lymphoma, and a number of solid tumors.

28. Antibiotics
Bleomycin
Mechanism
 The drug has its greatest effect on neoplastic cell in
the G2 phase of the cell replication cycle.Although
bleomycin intercalates DNA, the major cytotoxicity
is believed to result from iron catalyzed free radical
formation and DNA strand breakage.
Indications
 It is useful in Hodgkin’s and non-Hodgkin’s
lymphomas, testicular cancer, and several other
solid tumors.
Adverse Effects
 Bleomycin produces very little myelosuppression.
The most serious toxicities of Bleomycin are
pulmonary and mucocutaneous reactions.

29. Anti-Cancer Plant Alkaloids
Vinca Alkaloids:
The cellular mechanism of action of
vinca alkaloids is the prevention of
microtubule assembly, causing cells to
arrest in the late G2 phase by
preventing formation of mitotic
filaments for nuclear and cell division.
Vinca contains vin cristin and vin blastin.

30. Hormones
Estrogens
 Estrogens inhibit the effects
of endogenous androgens and
androgen-dependent metastatic
prostatic carcinoma.
Diethylstilbestrol is usually the
agent of choice.
 Cardiac and cerebrovascular
complications and carcinoma
of the male breast are
potential adverse effects.

31. Hormones
Progestins
Progestins are useful in the management
of endometrial carcinoma and back-up
therapy for metastatic hormone-dependent
breast cancer.

32. Side effects of chemotherapy
• Depression of immune system.
• Severe anemia
• Bleeding
• Constipation
• Hair loss,,nausea, vomiting, constipation.
• Dehydration.

33. ORGANS AFFECTING IN
CHEMOTHERAPY
• Cardio toxicity
• Hepato toxicity
• Nephro toxicity
• Otto toxicity
• Encephalo toxicity