ANTICANCER
DRUGS
JHANSI.GANAPATHI
Y11MPH140004
I ST M.PHARMACY.
PHARM.CHEMISTRY.
Cancer
Abnormal proliferation of cells\tissue deviating from
normal growth mechanism.
Cancer cells develop because of damage to DNA.
Most of the time when DNA becomes damaged the body
is able to repair it.
In cancer cells, the damaged DNA is not repaired.
Characteristics of Cancer Cells
The problem:
Cancer cells divide rapidly .
They are “immortal”
Cell-cell communication is altered
Uncontrolled proliferation
Invasiveness
Ability to metastasise
The Goal
Curative
of Cancer Treatments
Total irradiation of cancer cells
Curable cancers include testicular tumors, Wills
tumor
Palliative
Alleviation of symptoms
Avoidance of life-threatening toxicity
Increased survival and improved quality of life
Adjuvant therapy
Attempt to eradicate microscopic cancer after
surgery
e.g. breast cancer & colo - rectal cancer
Cell Cycle =
Growth, Division
Six Established Therapies
1. Surgery
2. Radiotherapy
3. Chemotherapy
4. Endocrine therapy
5. Immunotherapy
6. Biological therapy
CLASSIFICATION OF
ANTI –CANCER
1.Chemotherapy
DRUGS
Alkylating Agents
Antimetabolites
Antibiotics
Plant Alkaloids
Alkylating Agents
Nitrogen mustards
Mecholorethamine.HCl
Melphalan
Chlorambucil
Cyclophosphamide Ifosfamide
Cyclophosphamide
It is a prodrug and is activated by the P-450
enzymes to its active form phosphoramide
mustard
The active drug alkylates nucleophilic groups
on DNA bases
Particularly at the N-7 position of
guanine
This leads to cross linking of bases, abnormal
base pairing and DNA strand breakage
NITROSO UREAS
Carmustine
Lomustine
AZIRIDINES
Thiotepa
Triethylene melamine
DNA Methylators
Procarbazine Dacarbazine
Temozolamide
Organo-Platinum Complexes
Cisplatin Carboplatin
Miscellaneous DNA Alkylators
Busulfan Altritamine
Mechanism of Alkylating agents
The N-7 position of guanine in DNA is
strongly nucleophilic.
The alkylating agents acts by forming
the active aziridinium ion which attacks
the DNA of guanine and further causes
crosslinkage.
Uses
Non-Hodgkin’s lymphoma
Breast Cancer
Ovarian Cancer
Neuroblastoma
ANTIMETABOLITES
Folate Analogue Purine Analogue Pyrimidine Analogue
Methotrexate, 6- Mercaptopurine, 5-Fluoruracil,
Trimetrexate 6-Thioguanine Floxuridine
METHOTREXATE
Trimetrexate
Mechanism of folicacid analogue
Folic acid analog that binds with high
affinity to the active catalytic site of
dihydrofolate reductase (DHFR)
Thus it interferes with the synthesis of
tetrahydrofolate (THF)
Inhibition of these various metabolic
processes thereby interferes with the
formation of DNA, RNA, and key cellular
proteins.
Purine Analogs
6-Mercaptoguanine 6-Thioguanine
Mechanism of Purine Analogs
Purine are activated by HGPRT to toxic
nucleotides that inhibit several enzymes
involved in purine metabolism
Cancer cells also es alkaline phosphatase
that inactivate toxic nucleotides
Pyrimidine Analogs
Floxuridine
5-Flurouracil Cytarabine
Mechanism of Pyrimidine Analogs
Inhibits thymidylate synthase
and its cofactor,a
tetrahydrofolate derivative,
resulting in inhibition of
thymidine nucleotide synthesis.
.
Anticancer Antibiotics
Anthracyclines:
Doxorubicin (Adriamycin)
Daunorubicin
Epirubicin
Bleomycin
Dactinomycin
Mitomycin
Anthracyclines
Doxorubicin Daunorubicin
Epirubicin
Dactinomycin
Mechanism of Antibiotics
These drugs intercalate between base
pairs, inhibit topoisomerase II and
also generate free radicals.
They block RNA and DNA synthesis
and cause strand scission.
These are CCNS drugs.
Used as a component in ABVD
regimen in Hodgkin’s lymphoma
Plant Alkaloids
Vinca Alkaloids Podophyllotoxins Camptothecins Taxanes
Vinblastine Etoposide Topotecan Paclitaxel
Vinblastine Teniposide Irinotecan Docetaxel
Vincristine
Vinorelbine
Vinca Alkaloids
vinblastine
Vincristine
Vinka alkaloids
These drugs block the
formation of mitotic spindle
by preventing the assembly
of tubulin dimers into
microtubules.
They act primarily on the M
phase of cancer cell cycle.
.
VinBlastine VinCristine
Uses ; Uses:
Hodgkin’s disease Childhood leukemias
Lymphomas Childhood tumors-
Carcinoma Breast Wilm’s tumor,
Testicular tumors. Neuroblastoma,
Hodgkin’s disease.
Toxicity:
Toxicity:
Bone marrow
Peripheral neuritis
suppression, anorexia,
with
nausea, vomiting &
Paresthesia, Muscle
Diarrhea, Alopecia weakness.
Vincristine has
marrow sparing
effect.
Topoisomerase inhibitors
Etoposide Teniposeide
Etoposide & Teniposide
Acts by inhibiting topoisomerase II
These drugs are most active in late
S and early G2 phase.
Other topoisomerase inhibitors:
Camptothecin
Topotecan
•Act by inhibiting
topoisomerase-I
Taxanes
paclitaxel
docetaxel
Mechanism of taxons
These drugs act by interfering
with mitotic spindle.
They prevent micotubule
disassembly into tubulin
monomers.
ADR
Neutropenia
Peripheral neuropathy
Hormonal agents
Glucocorticoids
Sex hormone antagonists
GnRH analogs
Aromatase inhibitors
HORMONES HORMONE
ANTAGONISTS
Androgen: Antiandrogen:
Eg:Testosterone Eg:Flutamide
propionate Bicalutamid
Estrogens: Antiestrogens:
Eg:Ethinyloestradiol Eg:Tamoxifen
Progesteron derivative:
Eg: Megestrol Acetate Aromatase inhibitor:
Corticosteroids:
Eg: Letrozole
Eg: Prednisone, Anastrazole
Dexamethasone
Somotropin releasing
5-alpha reductase
hormone
inhibitor:
Eg: Octreotide
Eg: Finasteride
GnRH Analogue:
Eg: Leuprolide
Monoclonal Antibodies
Currently, several monoclonal antibodies are
available in the United States for the
treatment of cancer.
Trastuzumab
Rituximab
bevacizumab
cetuximab
Interferons
Human interferons have been classified
into three types—α, β, and —on the
basis of their antigenicity.
The α interferons are primarily
leukocytic, whereas the β and
interferons are produced by connective
tissue fibroblasts and T lymphocytes,
respectively.
. interferon-α-2a and -2b
•Miscellaneous
Hydroxyurea
Imatinib Mesylate
Rituximab
Epirubicin
Bortezomib
Zoledronic Acid
Geftinib
Leucovorin
Pamidronate
Gemcitabine
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REFERENCES
Burger’s Medicinal Chemistry and
Drug Discovery, fifth edition, volume-
1.
Wilson & Giswold’s Medicinal
Chemistry.
Pharmacology by Tripati.
Internet.
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