Phytopharmacology Class 7 (Anticancer Plants)

7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)

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Phytopharmacology

Class 7Anticancer Plants

Alejandro Pino


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Cancer

Second leading cause of death in theworld

Larger cells

Rapid division

No useful function

Ability to metastasize


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Cancer

More than 3 million new casesannually


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Cell life cycle


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QUINONES

BENZOQUINONES

NAPHTOQUINONES

ANTHRAQUINONES


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Benzoquinones Naphtoquinone Anthraquinone


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BIOLOGICAL PROPERTIES

BENZOQUINONE:

HYDROQUINONE: DERMATOLOGICAPPLICATION (SKIN DEPIGMENTATION)

NAFTOQUINONES: MICROBICIDE

TOXICITY (CYTOTOXICITY)

ALERGENIC


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CHEMICAL PROPERTIES OF

NAFTOQUINONES

YELLOW PIGMENTS IN PLANTS

DERIVATED FROM THE CARBOHYDRATEMETABOLISM OR THE LIPID METABOLISM

NON POLAR

EXTRACTED WITH CHLOROFORM ORDICHLOROMETHANE

GLYCOSIDIC FORMS ARE EXTRACTEDWITH METHANOL


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LAPACHO (TABEBUIA IMPETIGINOSA or

TABEBUIA AVELLANDEDAE) (Pau dArco)

TREE, 20 m TALL

BIGNONIACEAE FAMILY

DARK BARK (ACTIVE PRINCIPLES)

BIG TUBULAR FLOWERS 4 cm LONG

ORIGINAL FROM SOUTH AMERICA(ARGENTINA AND BRASIL)

NATIVE PEOPLE HAVE BEEN USING THEBARK TO TREAT TUMORAL DISORDERS


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Pau dArco flowers


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CHEMICAL COMPOSITION (BARK)

NAPHTOQUINONES LAPACHOL

LAPACHENOL

ALFA AND BETA LAPACHONA

MENAQUINONA

TABEBUINA

TECTOQUINA

ALKALOIDS

FLAVONOIDS

ANTHRAQUINONES


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PHARMACOLOGY

44% INHIBITORY EFFICACY IN SARCOMAMODELS IN RATS (LAPACHOL)

CANCER CELLS INHIBITED: (PLANT EXTRACTSAND LAPACHOL) in vitro

MELANOMA CELLS

LEUKEMIC CELLS

ACETYL-GLYCOSIDATED LAPACHOL IS MOREEFFECTIVE IN LEUKEMIC CELLS IN VITRO

CYTOTOXIC ACTIVITY (HIGH DOSES)

IMMUNO-STIMULANT ACTIVITY (LOW DOSES)


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CONCLUSIVE STUDIES

LAPACHOL IS NOT STATISTICLYEFFECTIVE IN HUMAN CANCERS (IN VIVO)

THE ACTIVE COMPLEX OF

NAPHTOQUINONES IS MORE ACTIVE INVITRO

MORE TOXICITY AND EFFICACYSCREENINGS ARE REQUIRED


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Rhein (anthraquinone)

Found in Rhubarb

Several hypotheses indicate that ithas anti-cancer properties

Disrupt mitochondria and cellmembranes

Produces impairment of cellmetabolism

Induces apoptosis and necrosis


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Catharanthus roseus (Vinka)

It is a species ofCatharanthus nativeto Madagascar.

It is an evergreenherbaceous plantgrowing to 1 m tall

The flowers are white to dark pink 25 cm diameter with five petal-likelobes

The fruit is a pair offollicles 24 cmlong and 3 mm broad
http://en.wikipedia.org/wiki/Catharanthushttp://en.wikipedia.org/wiki/Madagascarhttp://en.wikipedia.org/wiki/Evergreenhttp://en.wikipedia.org/wiki/Herbaceoushttp://en.wikipedia.org/wiki/Flowerhttp://en.wikipedia.org/wiki/Fruithttp://en.wikipedia.org/wiki/Follicle_(fruit)http://en.wikipedia.org/wiki/Follicle_(fruit)http://en.wikipedia.org/wiki/Fruithttp://en.wikipedia.org/wiki/Flowerhttp://en.wikipedia.org/wiki/Herbaceoushttp://en.wikipedia.org/wiki/Evergreenhttp://en.wikipedia.org/wiki/Madagascarhttp://en.wikipedia.org/wiki/Catharanthus


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Catharanthus roseus
http://upload.wikimedia.org/wikipedia/commons/5/5b/Catharanthus_roseus.jpg


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Catharanthus roseus (Vinka)


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Chemical composition (leaves)

Alkaloids: 0.2 1% total alkaloids Monomers

Reserpine

Catharanthine Ajmalicine

Dimers

Vincristine

Vinblastine

Phenols

Flavonoids


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Vincristine

Vinblastine
http://upload.wikimedia.org/wikipedia/commons/c/ca/Vincristin.svghttp://upload.wikimedia.org/wikipedia/commons/e/e6/Vinblastin.svghttp://upload.wikimedia.org/wikipedia/commons/e/e6/Vinblastin.svghttp://upload.wikimedia.org/wikipedia/commons/c/ca/Vincristin.svg


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Vincristine, vinblastine

Prevent tubulin polymerization

mitotic spindle formation

Cell-cycle specific (M phase)

Used in combinations (POMP)


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Taxus brevifolia (Tejo, Yew)

Conifer tree native to the PacificNorthwest ofNorth America.

It is a small to medium-sized,

growing 10-15 m tall and with atrunk up to 50 cm diameter

It has thin scaly brown bark

The leaves are lanceolate, flat, darkgreen, 1-3 cm long and 2-3 mmbroad, arranged spirally on the stem
http://en.wikipedia.org/wiki/Pinophytahttp://en.wikipedia.org/wiki/Pacific_Northwesthttp://en.wikipedia.org/wiki/Pacific_Northwesthttp://en.wikipedia.org/wiki/North_Americahttp://en.wikipedia.org/wiki/Barkhttp://en.wikipedia.org/wiki/Leafhttp://en.wikipedia.org/wiki/Leafhttp://en.wikipedia.org/wiki/Barkhttp://en.wikipedia.org/wiki/North_Americahttp://en.wikipedia.org/wiki/Pacific_Northwesthttp://en.wikipedia.org/wiki/Pacific_Northwesthttp://en.wikipedia.org/wiki/Pinophyta


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Taxus brevifolia (Tejo)
http://upload.wikimedia.org/wikipedia/commons/8/87/PacificYew_7591.jpg


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Taxus brevifolia tree
http://upload.wikimedia.org/wikipedia/commons/4/48/PacificYew_8544.jpg


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Chemical composition (bark and

needles)

Active complex Taxine constitutedby 11 nitrogenated compounds(terpenes and alkaloids)

Taxol: the most active compound, itis a diterpene-amide


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Extraction and purification of Taxol

(page 279)

Plant material, dried, grinded.

Extraction with methanol

Dry extract by evaporation (crudeextract)

Isolation of taxol by columnchromatography

Mobile phase: Methanol:water (65%Methanol)

Stationary phase: Silica gel RP-C18


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Paclitaxel (Taxol)

Also used in combinations

M phase specific

Stabilizes tubulin polymers=

prevents disassemblyOpposite of Vincristine


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Uncaria tomentosa (Cats claw)

It is a woody vine found in thetropical jungles of South and CentralAmerica, which derives its name

from its claw-shaped thorns

It is a liana

The leaves are elliptic with a smooth

edge, and grow in opposite whorls oftwo
http://en.wikipedia.org/wiki/Lianahttp://en.wikipedia.org/wiki/Leafhttp://en.wikipedia.org/wiki/Whorlhttp://en.wikipedia.org/wiki/Whorlhttp://en.wikipedia.org/wiki/Leafhttp://en.wikipedia.org/wiki/Lianahttp://upload.wikimedia.org/wikipedia/commons/6/62/Thorns_U_tomentosa.jpg


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http://upload.wikimedia.org/wikipedia/commons/6/62/Thorns_U_tomentosa.jpg


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Chemical composition (Bark)

Alkaloids: 0.9% oxindolalkaloids

Rhychnophylline, Iso-rhychnophylline

Mitraphylline, Iso-mitraphylline

Pteropodine, Iso-pteropodine

Uncarine A, Uncarine F

Polyphenols (Proanthocyanidins)

Triterpenoids (Quinovic acidglycosides)


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Pharmacology

Cytotoxicity (anti-cancer)

Induction of apoptosis

Other mechanisms

Anti-inflammatory

Antiviral activity

Immunostimulation Antioxidant properties


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Uncaria tomentosa bark

Mobile phase

Ethyl acetate:Isopropanol:Ammonia(100:2:1)

DetectionDragendorff reagentWith NaNO2

T2 = Rychnophylline Rf 0.35Isorychnophylline Rf 0.75

2 = Uncaria tomentosa barkExtract


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Podophyllum

Podophyllum peltatum

Rhizome and roots


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http://upload.wikimedia.org/wikipedia/commons/e/e7/Koeh-246.jpghttp://upload.wikimedia.org/wikipedia/commons/7/7d/Podophyllum_peltatum.jpg


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Resin podophyllin

Podophyllotoxin

Etoposide: semisynthetic derivativeof podophyllotoxin

Inhibitor of the enzymetopoisomerase II (DNA replication)


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Podophyllotoxin

Etoposide
http://en.wikipedia.org/wiki/File:Etoposide.svghttp://en.wikipedia.org/wiki/File:Podophyllotoxin_acsv.svg


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Soybean (Genistein)

Lower incidence of breast andprostate cancer

Increased latency in animal modelsof cancer

Inhibits proliferation of cancer cellsin vitro


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Pharmacology (Hypotheses)

Inhibition of angiogenesis

Interaction with steroid hormonereceptors

Inhibition of tyrosine kinases

Inhibition of ROS formation

Interaction with topoisomerase


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Cephalotaxus harringtonia

Chinese plant

Bark of the plant

Alkaloids with cytotoxic activity

Homoharringtonine (HHT)

Inhibition of protein synthesis

Inhibits the enzyme peptidyltransferase

Induction of apoptosis


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http://upload.wikimedia.org/wikipedia/commons/8/84/Cephalotaxus_pedunculata_SZ132.pnghttp://en.wikipedia.org/wiki/File:Cephalotaxus_harringtonia_BotGardBln1105WithSeeds.JPG


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Pharmacology

Prolongs life in animals bearingimplanted tumors

Phase II and III clinical trials

Nonlymphoblastic leukemia

Chronic myelogenous leukemia


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Mistletoe (Viscum album)

Lectins

Viscotoxins

Studies in Europe


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Chemopreventive plants

Green tea

Polyphenols (catechins andproanthocyanidins)

Grape seed extract Polyphenols (proanthocyanidins)


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End of presentationThank you!

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Phytopharmacology Class 7 (Anticancer Plants)