ANTICANCER DRUGS, ETOPOSIDE & TENIPOSIDE, HISTORY, STRUCTURE, CHEMISTRY, MECHANISM OF ACTION, MEDICINAL USES.

1. ANTICANCER DRUGS
ETOPOSIDE & TENIPOSIDE
Presented by,
ASWINI SASIDHARAN
DEPT. OF PHARMACEUTICAL CHEMISTRY
GRACE COLLEGE OF PHARMACY, PALAKKAD

2. CONTENTS
• INTRODUCTION
• STRUCTURE
• MOLECULAR FORMULA
• HISTORY
• CHEMISTRY
• MECHANISM OF ACTION
• MEDICINAL USES
• REFERENCES

3. INTRODUCTION
• Anticancer drugs are used for inhibiting the cancer cell growth.
• Cancer is a class of diseases with uncontrolled proliferation of cells, that
invades to other body parts more frequently.
•It is characterised by rapid and uncontrolled formation of abnormal cells,
which may causes the production of tumours.
Tumours are classified as:
1.Benign Tumour: Non Cancerous and it don’t spread towards other parts.
2.Malignant Tumour: Cancerous and invades to the adjacent tissues and
spreads more rapidly.

4. Epipodophyllotoxins

5. Etoposide
MOLECULAR FORMULA : C
29 H32
O13

6. Teniposide
MOLECULAR FORMULA : C32 H32
O13 S

7. HISTORY
•Etoposide was first synthesized in 1966 and USFDA approval was granted in
1983.
•Hartmann F Stahelin, who was integral in the development of podophyllotoxin
based chemotherapeutics.
•The nickname of etoposide (VP-16) comes from the last name of one of the
chemist, who performed early work on the drug (VonWart Burg).
•Chemical modifications to podophyllotoxin will produce compounds with
various mechanism of action.

8. CHEMISTRY
1
2
3
4
5
6
7
8
•Four consecutive chiral centers, C-1 to C-4.
•Four planar fused ring.
•Aromatization of Ring C leads to the loss of
activity.
•Ring A is not essential for antimitotic activity.
•Chirality at C-1 postion is important, as it implies
axial position for Ring E.
•Ring E should not be placed on the axial position.
A B C D
E

9. •Methoxy groups at 3 and 5 position is essential
for the activity.
•Hydroxyl group at 4 position is important for
the potency of the drug, its loss will reduces the
level of strand breaks.
•Hydroxyl group at ortho & para position in
phenol ring, shows stronger topoisomerase- II
inhibitory activity.
•Addition of glycosidic groups will changes the
mechanism of the compound.
•Stereochemistry at C-2 & C-3 configures a
translactone, has more potency than ciscounter
part.
1
2
3
4
5
6
7
8 1
2
3
4
5
6
I
I
I
I
I
I
g1
g2
g3
g4
g5
g6
g7
g8
11
12
13
I
I
I

10. Mechanism Of Action
• Drug forms a tertinary
complex with DNA &
Topoisomerase II enzyme.
• Inhibits the action of
Topoisomerse II enzyme &
DNA religation.
• Causes critical errors in DNA
synthesis at the stage of cell
division.
• Apoptosis of the cancer cell. Double strand breaking in DNA

11. MEDICINAL USES
ETOPOSIDE
Used for the treament of:
•Small cell lung cancer.
•Testicular cancer
•Lymphocytic leukemia.
•Choriocarcinoma.
•Neuroblastoma.
•Ovarian cancer.
•Endometrial cancer
•Gastric cancer.
TENIPOSIDE
Used for the treament of:
•Lymphocytic Leukemia.
•Hodgkin’s Lymphoma.
•Reticulocyte Sarcoma.
•Acute Leukemia.
•Brain Tumour.
•Bladder Cancer.
•Neuroblastoma.
•Solid tumours in children.

12. REFERENCES
• Text book of Medicinal Chemistry, Volume II by V. Alagarsamy, page
no: 500.
• Wilson and Gisvoid’s Text book of Organic, Medicinal &
Pharmaceutical chemistry, 12th Edition by John M Beale, Jr and John H
Block, page no: 389-391.
• Text book of Medicinal chemistry by Dr. S S Rajendran, Kavitha K, N
Santhi, page no: 313-314.
• Essentials of Medicinal Pharmacology, 7th Edition by K D Thripathi,
page no: 866.

13. THANK YOU