7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
1/59
Phytopharmacology
Class 7Anticancer Plants
Alejandro Pino
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
2/59
Cancer
Second leading cause of death in theworld
Larger cells
Rapid division
No useful function
Ability to metastasize
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
3/59
Cancer
More than 3 million new casesannually
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
4/59
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
5/59
Cell life cycle
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
6/59
QUINONES
BENZOQUINONES
NAPHTOQUINONES
ANTHRAQUINONES
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
7/59
Benzoquinones Naphtoquinone Anthraquinone
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
8/59
BIOLOGICAL PROPERTIES
BENZOQUINONE:
HYDROQUINONE: DERMATOLOGICAPPLICATION (SKIN DEPIGMENTATION)
NAFTOQUINONES: MICROBICIDE
TOXICITY (CYTOTOXICITY)
ALERGENIC
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
9/59
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
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
10/59
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
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
11/59
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
12/59
Pau dArco flowers
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
13/59
CHEMICAL COMPOSITION (BARK)
NAPHTOQUINONES LAPACHOL
LAPACHENOL
ALFA AND BETA LAPACHONA
MENAQUINONA
TABEBUINA
TECTOQUINA
ALKALOIDS
FLAVONOIDS
ANTHRAQUINONES
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
14/59
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
15/59
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)
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
16/59
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
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
17/59
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
18/59
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
19/59
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
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
20/59
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
21/59
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/Catharanthus7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
22/59
Catharanthus roseus
http://upload.wikimedia.org/wikipedia/commons/5/5b/Catharanthus_roseus.jpg7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
23/59
Catharanthus roseus (Vinka)
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
24/59
Chemical composition (leaves)
Alkaloids: 0.2 1% total alkaloids Monomers
Reserpine
Catharanthine Ajmalicine
Dimers
Vincristine
Vinblastine
Phenols
Flavonoids
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
25/59
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.svg7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
26/59
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
27/59
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
28/59
Vincristine, vinblastine
Prevent tubulin polymerization
mitotic spindle formation
Cell-cycle specific (M phase)
Used in combinations (POMP)
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
29/59
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/Pinophyta7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
30/59
Taxus brevifolia (Tejo)
http://upload.wikimedia.org/wikipedia/commons/8/87/PacificYew_7591.jpg7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
31/59
Taxus brevifolia tree
http://upload.wikimedia.org/wikipedia/commons/4/48/PacificYew_8544.jpg7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
32/59
Chemical composition (bark and
needles)
Active complex Taxine constitutedby 11 nitrogenated compounds(terpenes and alkaloids)
Taxol: the most active compound, itis a diterpene-amide
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
33/59
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
34/59
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
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
35/59
Paclitaxel (Taxol)
Also used in combinations
M phase specific
Stabilizes tubulin polymers=
prevents disassemblyOpposite of Vincristine
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
36/59
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
37/59
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.jpg7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
38/59
http://upload.wikimedia.org/wikipedia/commons/6/62/Thorns_U_tomentosa.jpg7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
39/59
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
40/59
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)
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
41/59
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
42/59
Pharmacology
Cytotoxicity (anti-cancer)
Induction of apoptosis
Other mechanisms
Anti-inflammatory
Antiviral activity
Immunostimulation Antioxidant properties
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
43/59
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
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
44/59
Podophyllum
Podophyllum peltatum
Rhizome and roots
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
45/59
http://upload.wikimedia.org/wikipedia/commons/e/e7/Koeh-246.jpghttp://upload.wikimedia.org/wikipedia/commons/7/7d/Podophyllum_peltatum.jpg7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
46/59
Resin podophyllin
Podophyllotoxin
Etoposide: semisynthetic derivativeof podophyllotoxin
Inhibitor of the enzymetopoisomerase II (DNA replication)
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
47/59
Podophyllotoxin
Etoposide
http://en.wikipedia.org/wiki/File:Etoposide.svghttp://en.wikipedia.org/wiki/File:Podophyllotoxin_acsv.svg7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
48/59
Soybean (Genistein)
Lower incidence of breast andprostate cancer
Increased latency in animal modelsof cancer
Inhibits proliferation of cancer cellsin vitro
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
49/59
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
50/59
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
51/59
Pharmacology (Hypotheses)
Inhibition of angiogenesis
Interaction with steroid hormonereceptors
Inhibition of tyrosine kinases
Inhibition of ROS formation
Interaction with topoisomerase
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
52/59
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
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
53/59
http://upload.wikimedia.org/wikipedia/commons/8/84/Cephalotaxus_pedunculata_SZ132.pnghttp://en.wikipedia.org/wiki/File:Cephalotaxus_harringtonia_BotGardBln1105WithSeeds.JPG7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
54/59
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
55/59
Pharmacology
Prolongs life in animals bearingimplanted tumors
Phase II and III clinical trials
Nonlymphoblastic leukemia
Chronic myelogenous leukemia
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
56/59
Mistletoe (Viscum album)
Lectins
Viscotoxins
Studies in Europe
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
57/59
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
58/59
Chemopreventive plants
Green tea
Polyphenols (catechins andproanthocyanidins)
Grape seed extract Polyphenols (proanthocyanidins)
7/30/2019 Phytopharmacology Class 7 (Anticancer Plants)
59/59
End of presentationThank you!