Anti cancer drugs obtained from plant sources

PRESENTED BY

S.NAVEEN JAIN UNDER THE GUIDENCE OF

R.KARTHIKEYAN M.pharm (ph.D) DEPARTMENT OF PHARMACOGONSY

VIGNAN PHARMACY COLLEGE VADLAMUDI

DEFINITION

• CANCER:- Cancer is characterized by rapid and uncontrolled formation of abnormal cells which may mass together to form a growth or tumor, or proliferate throughout the body, initiating abnormal growth at other sites.

* ANTI-CANCER DRUGS:- The Drugs that are used in inhibiting the abnormal cell growth or killing the cancer cells.

CLASSIFICATION:-S.No CLASS DRUGS PLANT SOURCE

1. Vinca alkaloids Vincristine Vinblastine

Catharanthus roseus (Apocynaceae)

2. Taxanes PaclitaxelDocetaxel

Taxus brevifolia(Taxaceae)

3. Epipodophyllotoxin Etoposide Podophyllum hexandrum(Berberidaceae)

4. Camptothecin analouges

TopotecanIrinotecan

Camptotheca acuminata (Nyssaceae)

5. Colchicine Demecoline Cocus cholchicumAutumnale (Liliaceae)

6. Maytansinoid McytanacineMaytansine

Maytenus buchananii,M.Serrata (Celastraceae)

7. Macrocyclic lactones Bryostanins Bryozoa Bugula neritina

8. Quassinoids Bruceantin brusato Brucea javanica (Simarubaceae)

9. Curcuma Curcumin Curcuma longa (Zingiberaceae)

10. Flavonoids ViceninOrentin

Ocimum sanctum(Labiatae)

11. Sesquiterpene Gossypal Gossypium barbadense(Gossypiaceae)

12. Ellipticine Ellipticine Ochrosia eliptica(Apocynaceae)

13. Pthalide isoquinolinealkaloid

Noscapine Papaver somniferum(Papaveraceae)

14. Acetogenins Acetogenin Annona species(Annonaceae)

MODE OF ACTION OF NATURAL ANTICANCER DRUGS :

Purine synthesis Pyrimidine synthesis

Ribonucleotides

Deoxyribonucleotides

DNA

RNA

Enzymes Proteins Microtubules

Camptothecin Etoposide

Block topoisomerase

functions

PaclitaxelVinca

CholchineInhibit the function

of microtubules

RECENT ADVANCES OF NATURAL ANTICANCER AGENTS:-

1. Natural agents have low toxicity.2.The MOA of recent natural agents are * Acts on DNA bases * Intercalation of DNA * Inhibit topoisomerases & Proteinkinases * Induction of Apoptosis (Cell suicide)3. Many new species are investigated to find out new agents for treatment of cancer.4.Cell culture techniques are involved to produce new botanical therapeutic agents to treat neoplasms5. Development of QSAR modelling on anti- cancer agents also produces good therapeutic agents with decreasing toxicity

PLANT-DERIVED ANTICANCER AGENTS IN CLINICAL USE:-

1. First agents that were clinically used are Vinca alkaloids, Vinblastine(VLB) & Vincristine (VCR), isolated from Madagascar periwinkle.

2. Two clinically active agents, etoposide (VM 26) & teniposide (VP 16-213), semi synthetic derivatives of epipodophyllotoxin are used in cancer treatment.

3. The use of various parts of T.brevifolia and other Taxus species is widely used in caner therapy.

4. Anti-cancer drug armamentarium is the class of clinically- active agents derived from camptothecin, which is isolated from chinese ornamental tree is widely used.

5. Other plant-derived agents in clinical use are homoharringtonine (Cephalotaxus harringtonia) and elliptinium, a derivative of ellipticine, isolated from species of several genera of the Apocynaceae family, including Bleekeria vitensis A.C.Sm.

PLANT-DERIVED ANTICANCER AGENTS IN CLINICAL DEVELOPMENT:-

1.Vinblastine/Vincristine: Catharanthus roseus/Jamaica, Philippines (originally from Madagascar)

2. Etoposide: Podophyllum species/ Eastern US, Himalayas

3. Paclitaxel/Docetaxel: Taxus species/NW US, Europe

4. Topotecan/Irinotecan: Camptotheca acuminata/China

5. Homoharringtonine: Cephalotaxus harringtonia/China

6. Flavopiridol: Synthetic based on rohutikine from Dysoxylum binectariferum/India

7. Combretastatins: Combretum caffrum/S. Africa

Plant Alkaloids

Vinca Alkaloids

Podophyllotoxins

Etoposide

Camptothecins

Topotecan

Taxanes

Paclitaxel

VinblastineVincristineVinorelbine

Teniposide Irinotecan Docetaxel

Vinca alkaloidsB. source: Catharanthus roseus

Family: Apocynaceae

Part used: Dried whole plant

Chemical constituent: Vincristine Vinblastine Ajmalicine Vindesine

MODE OF ACTION OF VINCA

• 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.

Uses of vincaIn Europe, folk remedy for

diabetes for centuries. In China, an astringent,

diuretic and cough remedy. In Central and South

America, homemade cold remedy to ease lung congestion and inflammation and sore throats

Throughout the Caribbean, an flower extract to treat eye irritation and infections

VinBlastine VinCristine

Uses : Hodgkin’s disease LymphomasCarcinoma BreastTesticular tumors

Uses: Childhood leukemiasChildhood tumors-Wilm’s tumor, Neuroblastoma, Hodgkin’s disease

Podophyllum

B. Source: Podophyllum hexandrum

Family: BerberidaceaePart used: dried rhizomes & rootsUses:• Used in treatment of small cell

carcinoma of lung, prostrate and testicular carcinomas

Chemical constitutent:• Podophyllotoxin• Etoposide• Teniposide

Podophyllotoxin

MOA of Podophyllum• Acts by inhibiting

topoisomerase II

• These drugs are most active in late S and early G2 phase

Taxanes• B. source: Taxus brevifolia• Family: Taxaceae• Part used: Stem barkUses:• Ovarian cancer• Lung carcinoma• Gastric & Cervical cancers• Prostate & colon cancerChemical constituent:• Taxol• Paclitaxel• Docetaxal

Taxol TAXOL

MOA of Taxanes• These drugs act by interfering with mitotic

spindle

• They prevent micotubule disassembly into tubulin monomers

Camptothecin

B. source: Camptotheca acuminata

Family: NyssaceaePart used: Dried stem woodUses: Ovarian cancers Colorectal cancer Cancer of neck & head Liver cancerChemical constituent: Camptothecin Topotecan Irinotecan

Camptothecin

Topotecan

TOPOTECAN

Camptotecan

MOA of Camptothecin

• Camptothecin act by inhibiting topoisomerase-I

CONCLUSION

• Plants have been a prime source of highly effective conventional drugs for the treatment of many forms of cancer.

• The actual compound isolated from the plant may not serve as the drug but leads to the development of potential novel agents.

• Natural agents are proving to be an important source of novel inhibitors & have the potential for development into selective anticancer agents.

ACKNOWLEDGEMENT

I ACKNOWLEDGE Dr. P.SRINIVASABABU,PRINCIPAL VIGNAN PHARMACY COLLEGE FOR HIS CONTINOUS SUPPORT TO EXPOSE SUCH TYPE OF

KNOWLEDGE ACQURING SEMINARS & CONFERENCES