ANTI CANCER AGENTS &ANTI VIRAL AGENTS

BY T.RAMESH M.PHARM-1ST SEMISTER DEPT.OF PHARMACEUTICAL CHEMISTRY

S.R COLLEGE OF PHARMACY ANANTHASAGAR ,HASANPARTHY, WARANGAL

CONTENTS
Introduction cancer
Classification of anti cancer agents

SAR of anticancer agents

Mode of action of anticancer agents

Introduction of virus
Classification of anti viral agents

Mode of action of anti viral agents

Conclusion

References

CANCER
Cancer or Neoplasm is a disease in which there is uncontrolled multiplication and spread within the body of abnormal forms of the bodys own cells.

Cancer harms the body when damaged cells divide uncontrollably to form lumps or masses of tissue called tumor.

CHARACTERISTICS OF CANCER CELLS

There are four characteristics that distinguish them from normal cell. Uncontrolled proliferation Dedifferentiation and loss of function

Invasiveness
Metastasis

CAUSES OF CANCER

CELL CYCLE

TREATMENT OF CANCER
Chemotherapy Radiation Surgery Targeted therapy

Immunotherapy
Hormonal therapy Stem cell/ bone marrow transplantation Palliative care

CLASSIFICATION OF ANTICANCER AGENTS

I.
A.

Alkylating agents
Nitrogen Mustards
Eg: Mechlorethamine, Cyclophosphamide, Chlorambucil, Melphalan Ifosfamide
H

B.

Alkyl Sulfonates
Eg :Busulfan

Cl

ClCH2CH2NCH2CH2Cl Mechloroethamine hydrochloride

Cl O O P NH Cl N

C.

Nitrosoureas

Eg :Carmustine (BCNU), Lomustine (CCNU), Semustine,Streptozocin

D. Ethylenimines
Eg: Thiotepa

E. Triazenes
Eg: Dacarbazine

cyclophosphamide

II. ANTI-METABOLITES
A. Folate Antagonists
Eg: Methotrexate

B.
C.

Purine Analogues
Eg: Thioguanine (6-TG), Mercaptopurine (6-MP), Fludarabine

Pyrimidine Analogues
Eg: Cytarabine, Fluorouracil (5-FU)
O F HN

SH H N N

N H

FLUROURACIL

MERCAPTOPURINE

III. ANTI-BIOTICS
A.
1. 2. 3.

Anthracyclines
Doxorubicin Daunorubicin Idarubicin
O O OCNH2

B. C. D. E.

Bleomycins Mitomycin Dactinomycin Plicamycin

O

OCH3

Mitomycin

IV. PLANT-DERIVED PRODUCTS

A. B. C. Vinca Alkaloids
Eg: Vincristine, Vinblastine

Epipodophyllotoxins
Eg: Etoposide,Teniposide

Taxanes
Eg: Paclitaxel

V.

ENZYMES
Eg: L-Asparaginase

VI. HORMONAL AGENTS

A. B. Glucocorticoids Estrogens/Anti-estrogen
Eg: Tamoxifen, Estramustine phosphate

C.
D. E. F.

Androgens/Anti-androgens
Eg: Flutamide

Progestins LH-RH Antagonist

Eg: Buserelin, Lueprolide

Octreotide acetate

VII. MISCELLANEOUS AGENTS

Eg: Hydroxyurea, Procarbazine, Mitotane, Cisplatin,Carboplatin, Mitoxantrione

VIII. MONOCLONAL ANTI-BODIES IX. IMMUNOMODULATING AGENTS

A. B. Levamisole Interferons
Eg: Interferon alfa-2a, Interferon alfa-2b
H2 N O

C
N H

OH

C.

Interleukins
Eg: Aldesleukin

Hydroxyurea

X. CELLULAR GROWTH FACTORS

Eg: Filgrastim (G-CSF), Lenograstim, Sargramostim (GM-CSF)
H3N Cl

Pt
H3N

Cl

cisplatin

CELL CYCLE

PHASE SPECIFIC DRUGS

CELL CYCLE SPECIFIC
S Phase: Cytosine arabinoside,
6-MP,MTX,5-Fu

CELL CYCLE NON SPECIFIC

Alkylating agents

M Phase: Vincristine, Vinblastine,

Paclitaxel, Taxol, Taxotere

Antibiotics

G2 Phase: Bleomycin G1 Phase: 5-Fu

Nitrosoureas Cisplatin, Procarbazine

SAR OF ALKYLATING AGENTS

R

Nitrogen mustards differs only in the nature of third groupR R may be aliphatic or aromatic An aliphatic substituent increases the speed of attacking Resonence by aromatic substituents delocalization significantly slows the intra molecular attack Nitrogen can decompose in aqueous media forms inactive de halogenated diols

MODE OF ACTION
ALKYLATING AGENTS
The agents are CCS, form reactive molecular species that alkylate nucleophilic groups on DNA bases, particularly the N-7 position of guanine. This leads to cross-linking of bases, abnormal base pairing, and DNA strand breakage.

 ANTI-METABOLITES 1. FOLATE ANTAGONIST:

Dihydrofolate reductase

Folic Acid (FH2)

INHIBITS

Tetrahydrofolate (FH4)

MTX(METHOTREXATE)
H2N N N

N N NH2 HN O C NH

(CH2)2

COOH

METHOTREXATE

 PURINE ANALOGUES
Incorporation of the thionucleotide analogue into DNA or RNA. Feedback inhibition of purine nucleotide synthesis.
SH H N N

MERCAPTOPURINE

 PYRIMIDINE ANALOGUES
- The active metabolite that inhibit DNA synthesis is the deoxyribonucleotides 5-fluoro-2-deoxyuridine 5 phosphate. - Target enzyme inhibited by 5-Fu is thymidylate synthetase.
NH2

O F HN

N H

FLUROURACIL

Uridylate (dUMP)

Thymidylate dTMP)
OHH2C

O
HO

Thymdylate synthetase
HO

CYTARABINE

 ANTIBIOTICS
- It binds to DNA and inhibit the synthesis of both DNA & RNA. - Its cytotoxic action is mediated byTopo isomerase-II
O O OCNH2

OCH3

mitomycin

 ANTI-MITOTIC (PLANT DERIVED)

- They have ability to bind specifically to tubulin and block its ability to polymerize with tubulin into microtubules. - Cell division is arrested in metaphase. Cells blocked in mitosis undergo changes characteristic of apoptosis.
VINCRISTINE
INHIBITS
POLIMERIZATION

TUBULIN

MICROTUBULE

USES: Acute leukemia,Hodgkins and non Hodgkins lymphoma

 ENZYMES
- L-asparaginase catalyzes the hydrolysis of L-Asparagine to aspartic acid & ammonia. L-glutamic acid is also hydrolyzed by this enzyme.
HYDROLYSIS

ASPARGINE

Aspartate +

Ammonia

Uses: Used in the treatment of lymphocytic leukemia

 HORMONAL AGENTS
- Tamoxifen binds to estrogen receptors within the cell & competes with endogenous estrogen.

- It directly inhibits the in-vitro growth of tumor cells.

Estrogen

+ Estrogen receptor competes Tamoxifen

Cell death

USES: Used in treatment of leukemia , lymphomas

Synthesis of cyclophosphamide

SIDE EFFECTS
Bone Marrow Suppression Gastrointestinal disorders Allopecia Phlebitis Nephrotoxicity Hepatotoxicity Cardiotoxicity Pulmonary toxicity Reproductive toxicity

ANTIVIRAL AGENTS

VIRUS

Obligate intracellular parasites Nucleic acid core: DNA or RNA Often contain virus-specific enzymes Surrounded by protein: capsid

sometimes an outer lipid envelope

Complete viral particle: virion

Classification of Viruses
DNA- VIRUSES Eg: papilomavirus, Adenovirus, parvovirus, Herpes virus RNA- VIRUSES Eg: Rubella virus, Hepatitis virus, Arenavirus, Influenza virus, RITRO-VIRUSES Eg: HIV-I , HIV-2

Classification of Anti Viral Agents

Nucleoside reverse transcriptase inhibitors Eg:zidovudine, Didanosine, Stavudine, Abacavir
Non-nucleoside reverse transcriptase inhibitors Eg:Nevirapine, Efavirenz DNA polymerase inhibitors Eg:acyclovir, Foscarnet, Tribavirin, Ganicyclovir,
H2N
HO NH

N O

DIdanosine
O

NH

N O

Inhibitors of HIV fusion with host cell Eg:Enfurvitide

H2CHO

ACYCLOVIR

Neuraminidase inhibitors and inhibitors of viral coat disassembly Eg:Oseltamivir, Zanzmivir

Biologics and immunomodulators Eg:Inerferon, Immunoglobulin, Polivisumab, inosine pranobex

Site of action of antiviral agents

O
O

NH2

NH

H2N H2CHO

N O

HO HO

OH

1-Arabinofuranosylcytosine

(cytarabine)

ACYCLOVIR
O

NH

H3C HN

O CH3 HN

N O HO

N
N

N
HO

DIdanosine

Nevirapine

Cl

Cl
N COOH

ClCH2CH2NCH2CH2Cl Mechloroethamine hydrochloride

Cl

chlorambucil
Cl O

Cl O O P NH Cl N

O P N Cl NH

Cyclophosphamide

ifosfamide
O

O OCNH2

H3N

Cl

OCH3

Pt
H3N

Cl

Cisplatin

mitomycin

SH
O F HN

H N N
N

NH2

N H

FLUROURACIL

OHH2C

O
HO

MERCAPTOPURINE
HO

CYTARABINE

H2N

N N NH2 HN O C NH

(CH2)2

COOH

METHOTREXATE

Nucleoside Reverse Transcriptase Inhibitors

These were the first type of drug available to treat HIV infection . Interfere with the action of an HIV protein called reverse transcriptase, which the virus needs to make new copies of itself.
O NH N

N O HO

DIdanosine

Non nucleoside Reverse Transcriptase Inhibitors (NNRTI)

Bind directly to HIV reverse transcriptase, prevents viral

RNA from conversion to the viral DNA that infects healthy

cells, by causing conformational changes in the enzyme.

H3C HN N

Nevirapine