anticancer agent

1
Anticancer agent

• Submitted by Kakadiya Dipesh
• Submitted to Dr. M.N.Noolvi

2
Content

• What is Cancer?
• Types of Cancer
• Causes and risk factors
• The Classification of Anticancer
• Drugs

3
What is Cancer?

• Cancer is a disease characterized by
  uncontrollable, irreversible, independent,
  autonomous, uncoordinated and relatively
  unlimited and abnormal over growth of tissues.
• Cancer spreads by invasion to the surrounding
  tissues and by metastasis to distant sites.

4
Types of Cancer Affected Area
Anal cancer Anus
Breast Cancer Breast
Bladder Cancer Urinary Bladder
Bone marrow Cancer Shafts of long bones
Colon Cancer Colon
Cervical Cancer Cervix
Eye Cancer Eye
Gynecological Cancer Female Reproductive organs
Lung Cancer Lung
Osteo sarcoma metaphyseal region of tubular long bones
Wilms tumour Kidney
Leukemia Blood
Larynx Cancer Larynx
Testicular cancer Testis
Rectal Cancer Rectum
5
Causes and risk factors

• Environment
• cigarette smoke
• chemicals
• UV light
• viruses
• Metabolic processes
• free radicals
• DNA copying and repair defects
• Inherited genetic mutations

6
The Classification of Anticancer Drugs

• Drugs acting directly on cells (Cytotoxic drugs)
• 1. Alkylating agents
• These compounds produce highly reactive
  carbonium ion intermediates which transfer alkyl
  groups to cellular macro molecules by forming
  covalent bonds.
• Alkylation results in cross linking/ abnormal
  base pairing/scission of DNA strand.

7
Nitrogen mustard
head and neck carcinomas, osteogenic sarcoma
Breast cancer, Multiple myeloma
Hodgkins disease, T-cell lymphoma
Multiple myeloma, Ovarian cancer, Breast cancer
Chronic lymphocytic leukemia
8
Recent drugs based on Nitrogen mustard

• Bestrabucil (phase I trial)
• Chlorambucil derivative

Bendamustine
Uramustine (Nitrogen mustardUracil Derivative)
9
Ethylenimine
Ovarian cancer, Breast cancer Lymphoma
Alkyl sulfonate
Chronic Myeloid Leukemia
10
Nitrosoureas
- meningeal leukaemias and brain tumours(can
cross BBB)
Triazine
Malignant melanoma Hodgkin's disease.
11
2. Antimetabolites

• These are analogues related to normal
  components of DNA or of coenzymes involved in
  nucleic acid synthesis.
• They competitively inhibit utilization of
  the normal substrate or get themselves
  incorporated forming dysfunctional
  macromolecules.
• Several of the useful drugs used in
  antimetabolite therapy are purines, pyrimidines,
  folates, and related compounds.

12
Folate antagonist
Methotrexate
(NEOTREXATE)
Acute lymphoblastic leukemia, Lung cancer.

13

• Purine antagonist
• These are highly effective antineoplastic drugs.
• They are converted in the body to the
  corresponding
• monoribonucleotides which inhibit the conversion
  of inosine monophosphate to adenine and guanine
  nucleotides.

6-mercaptopurine
Adult acute leukemia
Childhood acute leukemia
14

• Recent drugs based on purines and related
  compounds

15
Pyrimidine antagonist

• Pyrimidine analogues have varied applications as
  antineoplastic, antifungal and antipsoriatic
  agents.

• 5-Fluorouracil is converted in the body to the
  corresponding nucleotide 5-fluoro-2-deoxyuridine
  monophosphate, which inhibits thymidylate
  synthase and blocks the conversion of
  deoxyuridilic acid to deoxythymidylic acid.
• This leads to elective failure of DNA synthesis.

Adenocarcinoma, Skin cancer
16
Recent drugs
17
3. Natural anticancer agents

• Vinca alkaloids
• These are mitotic inhibitors, bind to
  microtubular protein-'tubulin', prevent its
  polymerization and assembly of microtubules,
  cause disruption of mitotic spindle and interfere
  with cytoskeletal function.

• The chromosomes fail to move apart during
  mitosis metaphase arrest occurs.
• They are cell cycle specific and act in the
  mitotic phase.

18
Hodgkins disease, Acute lymphocytic
leukemia, Lung cancer
19
Taxanes

• First isolated from bark of Western / Pacific
  yew (Taxus brevifolia)

• It is used for treatment of lung, ovarian and
  breast cancer.

• Taxanes hyper-stabilizes microtubule structure
  (freez them). Taxanes binds to the ß subunit of
  tubulin ,the resulting microtubule/ Taxanes
  complex does not have the ability to disassemble.
  This adversely affects cell function because the
  shortening and lengthening of microtubules is
  necessary for their function.

20
Ovarian cancer, Breast cancer, Non small cell
lung cancer
Semi-synthetic derivatives
21
Epipodophyllotoxin
Small cell lung cancer, Non-Hodgkins
lymphomas, Kaposis sarcoma, Cervical cancer
From Podophyllum peltarum May apple
Affects DNA topoisomerase II (not
intercalating) DNA strand breakage
Etoposide (Semi-synthetic) Eposin Etopofos
Vepesid
22
Camptothecin analogues

• First isolated Camptotheca acuminata (Chinese
  tree).

• Inhibits DNA topoisomerase II DNA
  strand

breakage
Ovarian cancer, Small cell lung cancer
Topotecan Hycamtin
Irinotecan Campto
Semisynthetic
23
4. Antibiotics

• These are products obtained from
  microorganisms and have prominent antitumour
  activity.
• Practically all of them intercalate between
  DNA strands and interfere with its template
  function.

Wilms' tumour, Rhabdomyosarcoma
Actinomycin D
24
Kaposis sarcoma, Small cell lung cancer, Breast
cancer, Malignant lymphomas
Doxorubicin
Prostate cancer, Multiple sclerosis
Mitoxantrone
25
Kaposis sarcoma, Acute myeloid leukemia
Daunorubicin
Carcinomas of the cervix, Breast, lung, stomach
Mitomycin
26
Recent anticancer antibiotics drugs
Calicheamicin
(Priclinical )
27
Kigamicin C ( priclinical)
Lactoquinomycin A
28

• 5. Miscellaneous
• These drugs have been developed by random
  synthesis and testing for anti tumour activity.

Procarbazine
Hydroxyurea
Hodgkin's disease, Non-Hodgkin lymphomas, Oat
cell carcinoma of lung
Chronic myeloid leukaemia, Psoriasis,
Polycythaemia
29
Metastatic testicular and Ovarian carcinoma
Cisplatin
Squamous carcinoma of head and neck, Small cell
lung cancer, Seminoma
Carboplatin
chronic myeloid leukaemia
Imatinib
30
Recent drugs
Non-Small Cell lung cancer (PROTEIN KINASE
INHIBITORS)
Gefitinib
Crizotinib
Erlotinib
Ovarian carcinoma, Seminoma
Oxaliplatin
31
B. Drugs acting on Hormones

• It involves the manipulation of the endocrine
  system through exogenous administration of
  specific hormones, particularly steroid hormones,
  or drugs which inhibit the production or activity
  of such hormones.

• Because steroid hormones are powerful drivers
  of gene expression in certain cancer cells,
  changing the levels or activity of certain
  hormones can cause certain cancers to cease
  growing, or even undergo cell death.

32

1. Corticosteroids

• Corticosteroids are strong anti-inflammatory
  drugs.
• They are used to reduce swelling that causes
  cancer pain.

Examples





33
palliation of lymphomas and leukemias
Prednisolone
haematological malignancies
Dexamethasone
34
2. Estrogens

• The agonist is occasionally used to treat
  prostate cancer through suppression of
  testosterone production.

Ethinylestradiol
Fosfestrol
carcinoma prostate
35
3. Selective estrogen receptor modulators

• Acts by selective antagonism of the estrogen
  receptor.

Breast cancer
Toremifene
Tamoxifen
36
4. Selective estrogen receptor down regulators

• Estrogen receptor down regulators blocks the
  effects of estrogen in breast tissue.

Metastatic breast cancer
Fulvestrant
37
5. Aromatase inhibitors

• Aromatase is the enzyme that synthesizes
  estrogen.
• Aromatase inhibitors (AIs) are a class of
  drugs used in the treatment of breast cancer and
  ovarian cancer in postmenopausal women.
• As breast and ovarian cancers require estrogen
  to grow, Aromatase inhibitors are taken to either
  block the production of estrogen or block the
  action of estrogen on receptors.

38
Breast cancer
Letrozole
Breast cancer
Anastrozole
39
Early stage of breast cancer
Exemestane
Recent drug
Vorozole
Aminoglutethimide
40
6. Antiandrogen

• Antiandrogens, or androgen antagonists, first
  discovered in the 1960s, prevent androgens from
  expressing their biological effects on responsive
  tissues.
• Antiandrogens alter the androgen pathway by
  blocking the appropriate receptors, competing for
  binding sites on the cell's surface, or affecting
  androgen production.

• Antiandrogens are most frequently used to treat
  prostate cancer.

41
Bicalutamide
Flutamide
Finasteride
Nilutamide
42
development status of antiandrogen drugs
43
(No Transcript)
44
(No Transcript)
45
Recently Approved Drugs by FDA

Drugs Uses
2014
Belinostat Peripheral T-cell lymphoma
Ramucirumab Gastric cancer
Ibrutinib Chronic lymphocytic leukemia
Idelalisib Relapsed Chronic lymphocytic leukemia
Ceritinib Non-small cell lung Cancer
46
Drugs Uses
2013
Obinutuzumab Chronic lymphocytic leukemia
Afatinib Metastatic non-small cell lung cancer
Radium Ra 223 dichloride prostate cancer
Trametinib Metastatic melanoma
Pomalidomide Relapsed and refractory multiple myeloma
Lenalidomide Mantle cell lymphoma
Regorafenib Gastrointestinal stromal tumor
Dabrafenib Metastatic melanoma
Denosumab Prostate cancer
47
References

• Wilson and Gisvold's textbook of organic
  medicinal and pharmaceutical
• chemistry, Twelfth Edition, Charles Owens
  wilson, Ole Gisvold

2. Essentials of Medical Pharmacology, Sixth
Edition, K.D TRIPATHI
3. Foyes Principles of medicinal chemistry,
Sixth Edition, Thomas L. Lemke, David A.
Williams
http//www.fda.gov/drugs/informationondrugs/appro
veddrugs/ ucm279174.htm
4.
48
(No Transcript)