Vinca Alkaloids.pptx

Pharmacognosy and phytochemistry of Vinca Alkaloids.

1. Vinca Alkaloids / Madagascar Periwinkle

2. Synonyms and Regional name: Vinca rosea Lochnera rosea Periwinkle Baramasi Madagascer periwinkle Sadaphuli Rattanjot Billaganneru Hindi- Sadabahar Beng.-Nayantara.

3. Introduction: Vinca alkaloids are obtained mainly from a species of periwinkle known as Madagascar Periwinkle. It is also known as “ Sadabahar ” or “ Sadaphuli ”. Other species of periwinkle are also known to contain vinca alkaloids. There are at least 150 alkaloids known to be extracted from Vinca. Vinca alkaloids are chemically indole alkaloids and are known to possess anti-cancer, anti-hypertensive and anti-diabetic roles.

4. Earlier this plant was used for antidiabetic action but unable to confirm it. 1955-60 Canadian co worker reported its leucopenic action in rat. It promotes discovery for anticancer activity. Eli lilly company takes intensive investigation for isolation of anticancer alkaloids. About 6 alkaloids has been found active but only 2 are commercially available( vincristine and vinblastine). 1 gram of vinblastine from 500kg crude drug. 50 mg of vincristine from 1 tone of crude drug.

5. Biological Source Aerial parts of  Catharanthus roseus  formerly known as  Vinca rosea . Family: Apocynaceae

6. Geographical Source It is indigenous to Madagascar and India. This plant is cultivated as an ornamental plant. found in tropical and subtropical regions like Africa, Australia, Eastern Europe, South Florida, India, Taiwan and Thailand.

7. Morphology/Macroscopical Characters A herbaceous subshrub, approximately 40-80 cm high. The leaves are oppositely arranged, oblong with petiolate acute base. The flowers are produced throughout the year, and are simple, generally 2-7 cm broad with usually 5 petals joined together at the base to form a tubule. The fruit is a divergent follicle.

8. Macroscopical characters: ( i ) Type – Annular or perennial herb; (ii) Size – 0.5 to 1 meter length; (iii) Leaves – Ovate, oblong, glossy above glaucous below; (iv) Flowers – 2 to 3 in cymes, axillary and terminal clusters. Bases on flower colour, three varieties are known namely – alba-white, ocillata -white with pink or carmine red eyes and roseus -with rose coloured flowers. (v) Fruit- a follicle, cylindrical and many seeded. (vi) Taste – Bitter; (vii) Odour – slight.

9. Microscopic Characters Microscopical characters: The transverse section of Vinca leaf Lamina: Upper epidermis: Single layered with more or less rectangular cells, the outer walls of which are circularized. Only covering trichomes are unicellular, long and dagger shaped, warty and with a bulbous base. Sometimes very short trichomes are also seen. A few stomata are seen on the upper epidermis. Mesophyll: Mesophyll is differentiated into palisade and spongy parenchyma. Palisade: Single layered cells elongated and compact. Spongy parenchyma: 5-9 layered, loosely arranged with intercellular spaces. Calcium oxalate crystals of any kind are totally absent. Vascular strands are seen here at times

10. Microscopic Characters Lower epidermis: Same as upper epidermis but the number of stomata are more Midrib: Epidermal layers of lamina are continuous in the midrib region also. Strips of collenchyma appear below the upper epidermis and above the lower epidermis. This is followed by cortical parenchyma. A well developed vascular bundle is seen in the centre of midrib.

11. Introduction to indole alkaloids Indole alkaloids are a class of nitrogen-containing secondary metabolites that have a bicyclic structure consisting of a benzene ring fused to a pyrrole ring. They are derived from tryptophan amino acid or its decarboxylation product, tryptamine and are classified into different groups based on their biosynthetic pathway.

12. Biogenetic precursor of all indole alkaloids is the amino acid tryptophan. Indole alkaloids are a class of alkaloids containing a structural moiety of indole; many indole alkaloids also include isoprene groups and are thus called terpene indole or secologanin tryptamine alkaloids. Indole alkaloids are distinguished depending on their biosynthesis.

13. The two types of indole alkaloids are isoprenoids and non-isoprenoids. Non-isoprenoid indole alkaloids derivatives are the biogenic amines tryptamine and 5-hydroxytryptamine (serotonin). Isoprenoid indole alkaloids: Isoprenoid indole alkaloids include residues of tryptophan or tryptamine and isoprenoid building blocks derived from the dimethylallyl pyrophosphate and isopentenyl pyrophosphate.

14. Biological activities of indole alkaloids. Indole alkaloids are often characterized by their potent biological activities, These are relevant to the field of medicine, including anticancer, antibacterial, antiviral, antimalarial, antifungal, anti-inflammatory, antidepressant, analgesic, hypotensive, anticholinesterase, antiplatelet, antidiarrheal, spasmolytic, antileishmanial, lipid-lowering, antimycobacterial, and antidiabetic activities etc.

15. chemical constituents/Chemistry Vinca is rich in indole alkaloids  particularly vincristine and vinblastine . About 150 alkaloids reported. Coupling of indole alkaloids such as catharanthine (indole) and vindoline ( dihydroindoline or indoline ) produces the ‘‘binary vinca alkaloids’’ also called bisindoles . Bisindole alkaloids: They are produced in living organisms through dimerization of monomeric indole bases. It contain conplex indole alkaloids. Contain nontryptophan derived part supplied by mevalonic acid (C10 geraniol)

16. Other alkaloids Ajmalicine (Hypotensive) Serpentine (Hypotensive) lochnerine Tetrahydroalstonine Best known oncolytic agents: vincristine (leurocristine) vinblastine (vinca leukoblastine) Vinleurosine or leurosine Vinrosidine or leurosidine

17. Semi synthetic alkaloids Vindisine (anti leukemic for children) Vinorelbine (newer orally active drug) Monomeric alkaloids (indole): Catharanthine Lochnerine Monomeric alkaloids (indoline): Vincoline vindolinine

18. Chemical constituents: 1. Indole and indoline alkaloids: (i) Ajmalicine (ii) Lochnerine (iii) Serpentine and 2. Tetrahydroalstonine: (i) Dimeric Indole bases of monoterpene type (ii) Vinblastine (iii) Vincristine.

19. Antidiabetic Activity: Vindogentianine , Vindoline , vindolidine , vindolicine , and vindolinine represent four new indole type alkaloids isolated from leaves of vinca.

20. chemical Tests all general tests for alkaloids

21. Adulterants/Allied drugs/ Substitutes Other Catharanthus species such as   C. longifolius ,   C. trichophyllus  and   C. lanceus  are known to contain vindoline type alkaloids.

22. Uses Vinca is useful in the herbal treatment of lymphomas. Vinblastine is used for the treatment of Hodgkin’s disease and non-Hodgkin’s lymphomas, given by i.v. Route, available as vinblastine sulphate. vincristine is used principally in the treatment of acute lymphocytic leukaemia, available as vincristine sulphate, given by i.v. route. Vincristine is superior than vinblastine but more neurotoxin.

23. Uses: Antineoplastic (antimitotic= Cytostatic = anticancer antitumor), act by arresting mitosis at metaphase or by inhibiting amino acid metabolism. In the treatment of Hodgkin’s disease. In the treatment of leukaemia in children, lung cancer, cervical and breast cancer. Vinca is also used in hypertension.

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