Medicinal Chemistry-II B. Pharmacy, third year semester Vth

1. Anti-neoplastic Agents
B. Pharm Third Year ( Vth semester )
By- S. K. Dhawale
D. K. Patil Institute of Pharmacy, Sayal road loha, Nanded.

2. Content
Introduction
Classification
Alkylating agent
Antimetabolite
Antibiotics
Plant products
Miscellaneous
Mode of action
2

3. Introduction
Cancer-
Progressive, abnormal and uncontrolled proliferation of cells/tissues.
Types of Neoplasm-
Benign
Malignant
Both cancerous cell and normal cells must pass through the following phases of cell cycle.
M phase: Mitotic cell division temporarily or permanently
G1 phase: Synthesis of enzymes and other cellular components needed for DNA synthesis
S phase : DNA synthesis takes place
G2 phase: synthesis of cellular components for mitosis
G0 phase: cell stop cell division.
3

4. Antineoplastic/ Anticancer/Cytotoxic drugs
Antineoplastic drugs are those drugs which are used to treat neoplasm or various types of
cancers.
Antineoplastic drugs kills or control growth, spread of abnormal cells, normal or healthy
cell or neoplastic cells.
Classification
Cytotoxic drugs
A) Alkylating agent:
Nitrogen Mustard: Cyclophasphamide, melphalan chlorambucil.
Ethyleneimine: Mechlorethamine
Alkyl Sulphonates: Busulphan
Nitrosourea: Lomustine, carmustine
Triazine: Decarbazine
4

5. B) Antimetabolites ( Acts on metabolic pathway involved in DNA
synthesis)
 Folate antagonist: Methotrexate
Purine antagonist: Morcopturine, Azathioprine
Pyrimidine Antagonist: 5- Flurouracil. Cytarabine.
C) Plant derivatives
 Vinca Alkaloids: Vincristine, Vinblastine
Texenes: Palcitaxel
Epipodophyllotoxine: Etoposide
Antibiotics: Actinomycine, Doxorubicin, Bleomycin
5

6. Hormones
Glucocorticoids: Prednisolone and its derivatives
Estrogen: Fosfestrol, ethyl estradiol
Progestins: Progestone
Antiandrogens: Flu amide
Miscellaneous
Hydroseyurea, cisplatin, Monoclonal antibodies
6

7. According to Mechanism of action
A) Drug affecting biosynthesis of nucleic acid
Hydroxyurea
B) Drug destroying DNA structure and its function
Alkylating agent, antitumor antibiotics, Cisplatin
C) Drug interfering with Transcription
Dactinomycine, Doxorubicin
D) Drug affecting protein synthesis
Vincristin and vinblastine, Etoposide, L- Asparaginase.
7

8. Alkylating Agent
Generally alkylating agent work by three mechanism
1) By alkylation of alkyl group to DNA base
2) DNA damage by formation of cross links
3) Induction of mispairing of the nucleotides leading to mutation
→It Produces highly reactive carbonium ion,
→which transfer alkyl group to position 7 of guanine by forming covalent bond.
→Cross linking abnormal base pairing of DNA strand
→Inhibition of DNA synthesis.
→This interferes in separation of strand and prevents cell replication.
8

9. Antimetabolites
Folate antagonist: Methotrexate
Purine antagonist: Morcopturine, Azathioprine
Pyrimidine Antagonist: 5- Flurouracil. Cytarabine.
Converted into Monoribonucleotides which inhibit the conversion of
adenine and guanine nucleotide,
Inhibits Dihydrofolate reductase, interfering synthesis of thymidylate,
purine nucleotides
Inhibit DNA synthesis.
9

10. Plant product
Vincristine
Vinblastin
Mechanism of action:
Bind specifically to the micro tubular protein tubulin in dimeric form
Terminate assembly of microtubules and result in mitotic arrest at metaphase,
Cause dissolution of mitotic spindle and finally interfere with chromosome
segregation.
10

11. Antibiotics
Antibiotics: Actinomycine, Doxorubicin, Bleomycin
Mechanism of action:
Bind tightly to double stranded DNA through interaction between adjacent
guanine cytosine base pair, and inhibit all forms of DNA dependent RNA
synthesis.
11

12. Cell Cycle specific drugs
M- Vincristin
Vinblastin
Paclitaxel
G1- Etoposide
S– Methotrexate
6- Mercaptopurine
5- Flurouracil
G2- Etoposide
Topotecan
Irinotecan
12

13. General toxicities of cytotoxic drugs
Bone marrow toxicity with decreased leukocyte production and thus decreases
resistance to infection
Impaired wound healing
Loss of hair (alopecia)
Damage to gastrointestinal epithelium
Depression of growth in children
Teratogenicity (fetal abnormalities)
13