anticancer& antiviral

8/2/2019 Anticancer& Antiviral

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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


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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


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CANCER

Cancer or Neoplasm is a disease in which there is uncontrolled

multiplication and spread within the body of abnormal forms

of thebodys own cells.

Cancer harms the body when damaged cells divide

uncontrollably to form lumps or masses of tissue called tumor.


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CHARACTERISTICS OF CANCER CELLS

There are four characteristics that distinguish them fromnormal cell.

Uncontrolled proliferation

Dedifferentiation and loss of function

Invasiveness

Metastasis


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CELL CYCLE


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TREATMENT OF CANCER

Chemotherapy

Radiation

Surgery

Targeted therapy

Immunotherapy

Hormonal therapy

Stem cell/ bone marrow transplantation

Palliative care


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CLASSIFICATION OF ANTICANCER

AGENTSI. Alkylating agents

A. Nitrogen Mustards

Eg: Mechlorethamine, Cyclophosphamide, Chlorambucil, Melphalan

Ifosfamide

B. Alkyl Sulfonates

Eg :Busulfan

C. Nitrosoureas

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

D. Ethylenimines

Eg: ThiotepaE. Triazenes

Eg: Dacarbazine

ClCH2CH2NCH2CH2Cl

H

Mechloroethamine hydrochloride

Cl

NH

P

O

N

Cl

Cl

O

cyclophosphamide


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II. ANTI-METABOLITES

A. Folate Antagonists

Eg: Methotrexate

B. Purine Analogues

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

C. Pyrimidine Analogues

Eg: Cytarabine, Fluorouracil (5-FU)

HN

NH

F

O

O

FLUROURACIL

H

N

NN

N

SH

MERCAPTOPURINE


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III. ANTI-BIOTICS

A. Anthracyclines

1. Doxorubicin

2. Daunorubicin

3. Idarubicin

B. Bleomycins

C. Mitomycin

D. Dactinomycin

E. Plicamycin

III. ANTI-BIOTICS

A. Anthracyclines

1. Doxorubicin

2. Daunorubicin

3. Idarubicin

B. Bleomycins

C. Mitomycin

D. Dactinomycin

E. Plicamycin N

O

O

OCH3

OCNH2

O

Mitomycin


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IV. PLANT-DERIVED PRODUCTS

A. Vinca Alkaloids

Eg: Vincristine, Vinblastine

B. Epipodophyllotoxins

Eg: Etoposide,Teniposide

C. Taxanes

Eg: Paclitaxel

V. ENZYMES

Eg: L-Asparaginase


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VI. HORMONAL AGENTS

A. Glucocorticoids

B. Estrogens/Anti-estrogenEg: Tamoxifen, Estramustine phosphate

C. Androgens/Anti-androgens

Eg: Flutamide

D. ProgestinsE. LH-RH Antagonist

Eg: Buserelin, Lueprolide

F. Octreotide acetate


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VII. MISCELLANEOUS AGENTSEg: Hydroxyurea, Procarbazine, Mitotane, Cisplatin,Carboplatin,

Mitoxantrione

VIII. MONOCLONAL ANTI-BODIES

IX. IMMUNOMODULATING AGENTS

A. Levamisole

B. InterferonsEg: Interferon alfa-2a, Interferon alfa-2b

C. Interleukins

Eg: Aldesleukin

X. CELLULAR GROWTH FACTORSEg: Filgrastim (G-CSF), Lenograstim, Sargramostim (GM-CSF)

C

O

H2NNH

OH

Hydroxyurea

Pt

H3N

H3N Cl

Cl

cisplatin


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CELL CYCLE


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PHASE SPECIFIC DRUGS

CELL CYCLE SPECIFIC CELL CYCLE NON

SPECIFIC

SPhase: Cytosine arabinoside,6-MP,MTX,5-Fu

Alkylating agents

M Phase: Vincristine, Vinblastine,Paclitaxel, Taxol, Taxotere

Antibiotics

G2 Phase: Bleomycin Nitrosoureas

G1 Phase: 5-Fu Cisplatin, Procarbazine


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SAR OF ALKYLATING AGENTS

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 significantlyslows the intra molecular attack

Nitrogen can decompose in aqueous media forms inactive de

halogenated diols

R


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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.


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ANTI-METABOLITES

1. FOLATE ANTAGONIST:Dihydrofolate reductase

Folic Acid Tetrahydrofolate

(FH2) (FH4)

MTX(METHOTREXATE)

INHIBITS

N

N

N

N

HN C

O

NH (CH2)2 COOHNH2

H2N

METHOTREXATE


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PURINE ANALOGUES

Incorporation of the thionucleotide analogue into DNA or RNA.

Feedback inhibition of purine nucleotide synthesis.

HN

NN

N

SH

MERCAPTOPURINE


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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.

Uridylate Thymidylate

(dUMP) dTMP)

Thymdylate synthetase

N

N

NH2

O

HO

HO

OHH2C

CYTARABINE

HN

NH

F

O

FLUROURACIL


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ANTIBIOTICS

- It binds to DNA and inhibit the synthesis of both DNA &RNA.

- Its cytotoxic action is mediated byTopo isomerase-II

N

O

O

OCH3

OCNH2

O

mitomycin


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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.

TUBULIN MICROTUBULEPOLIMERIZATION

INHIBITS

VINCRISTINE

USES: Acute leukemia,Hodgkins and non Hodgkins lymphoma


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ENZYMES

- L-asparaginase catalyzes the hydrolysis of L-Asparagine to

aspartic acid & ammonia. L-glutamic acid is alsohydrolyzed by this enzyme.

ASPARGINE

HYDROLYSIS

Aspartate + Ammonia

Uses:

Used in the treatment of lymphocytic leukemia


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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 Cell death

Tamoxifen

competes

USES:

Used in treatment ofleukemia ,

lymphomas


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Synthesis of cyclophosphamide


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SIDE EFFECTS

Bone Marrow Suppression

Gastrointestinal disorders

Allopecia

Phlebitis

Nephrotoxicity

Hepatotoxicity

Cardiotoxicity

Pulmonary toxicity

Reproductive toxicity


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ANTIVIRAL AGENTS


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Obligate intracellular parasites

VIRUS

Nucleic acid core: DNA or RNA

Often contain virus-specific

enzymes

Surrounded by protein: capsid

sometimes an outer lipid envelope

Complete viral particle: virion


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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

Cl ifi ti f A ti Vi l A t


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Classification of Anti Viral AgentsNucleoside reverse transcriptase inhibitors

Eg:zidovudine, Didanosine, Stavudine, Abacavir

Non-nucleoside reverse transcriptase inhibitors

Eg:Nevirapine, Efavirenz

DNA polymerase inhibitors

Eg:acyclovir, Foscarnet, Tribavirin, Ganicyclovir,

Inhibitors of HIV fusion with host cell

Eg:Enfurvitide

Neuraminidase inhibitors and inhibitors of viral coat disassembly

Eg:Oseltamivir, Zanzmivir

Biologics and immunomodulators

Eg:Inerferon, Immunoglobulin, Polivisumab, inosine pranobex

NH

N

O

H2N

N

N

OH2CHO

ACYCLOVIR

NH

N

O

N

N

O

HO

DIdanosine


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Site of action of anti iral agents


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Site of action of antiviral agents


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NH

N

O

H2N

N

N

OH2CHO

ACYCLOVIR

N

ON

NH2

OH

HO

O

HO

1-Arabinofuranosylcytosine (cytarabine)

NH

N

O

N

N

O

HO

DIdanosine

N

NN

HN

O

N

H3C

Nevirapine

HN

N

O

CH3

OHO


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ClCH2CH2NCH2CH2Cl

H

Mechloroethamine hydrochloride

Cl

COOHN

Cl

Cl

chlorambucil

NH

P

O

N

Cl

Cl

O

Cyclophosphamide

N

P

O

NH

Cl

O

Cl

ifosfamide

Pt

H3N

H3N Cl

ClN

O

O

OCH3

OCNH2

O

Cisplatin mitomycin

SH


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HN

NH

F

O

O

FLUROURACIL

HN

NN

N

SH

MERCAPTOPURINE

N

N

NH2

O

HO

HO

OHH2C

CYTARABINE

N

N

N

N

HN C

O

NH (CH2)2 COOHNH2

H2N

METHOTREXATE


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Nucleoside Reverse Transcriptase Inhibitors

These were the first type of drug available to

treat HIV infection .

Interfere with the action of an HIV proteincalled reverse transcriptase, which the virus needs

to make new copies of itself.

NH

N

O

N

N

O

HO

DIdanosine


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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.

N

NN

HN

O

N

H3C

Nevirapine

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