A SEMINAR ON ANTICANCER AND

PHARMACOKINETICS STUDY ON
ANDROGRAPHOLIDES
PRESENTED BY : MR. PRAVIN DUKARE 2- SEM M. PHARM (Q.A.T.)
GUIDED BY : DR. V. P. CHOUDHARI H.O.D. OF Q.A.T. DEPARTMENT

- Uncontrolled growth of abnormal cell
- Most serious disease
- Extensive research is done all over the world
structure based drug designing offers
computational approach to identify the potential
leads which can be developed into a drug

Cancer : -
Phases of Cell Cycle
The four phases of the cell cycle.
G1 - the initial growth phase.
S - the phase in which DNA is synthesised.
G2 - the second growth phase in preparation for cell division.
M - mitosis; where the cell divides to produce two daughter
cells that continue the cell cycle.
Cancer is the uncontrolled growth of cells coupled with
malignant behaviour: invasion and metastasis
It is caused by the interaction between genetic susceptibility
and environmental factors.
These factors lead to accumulations of genetic mutations in
oncogenes and tumor supressor genes which gives cancer cells
their malignant characteristics such as uncontrolled growth .

ANTICANCER DRUGS
1. Alkylating agents-
cyclophosphamide+busulphal+chlorambucil
2. Antimetabolites- methotrexate+6-
thioguanine+flourouracil
3. Antibiotics- doxorubiciln+dleomycil+actinomycil
4. Enzymes- L-asparaginase
5. Vinca Alkaloides Vincristine+vinblastine
6. Hormones- glucocorticoids+progestins+estra
mustine
7. Miscellaneous-Hydroyurea+ procarbazine+ cisplatin
8. Monoclonal antibodies

ADVERSE EFFECTS OF ANTICANCER
AGENTS

Bone marrow toxicity
Intestinal epithelium
Hair follicule toxicity
CNS toxicity
Nephrotoxicity
Hepatotoxicity
Skin rashes
Pulmonary toxicity
Cardiac toxicity
Immuno suppression


Andrographolides
Andrographolides is active constituent of plant
andrographis peniculata ( kalmegh )
Family : Acanthaceae
Mainly in south eastern Asia
In India Tamilnadu , karnataka , Maharashtra , orrisa .
It is extremely bitter in taste
Widely used in ayurvedic preparation
It is recommended in charka samhita dating
to 175 B. C. for treatment of Jaundice
Other activity like Liver protection (
Antidote ), anticancer, ant diabetic,anti
malarial
ANDROGRAPHOLIDES
Properties -
Molecular formula : C 20 H 30 O 5
Formula weight : 350. 45
Chemical name : 3alpha ,14 ,15, 18 tetrahydroxy -
5 Beta, 9 Beta H, 10 alpha labda 8 ,12 diene 16
oic acid , gamma lactone
Physiochemical properties:
Melting point : 231c.
Moisture content : By karl fischer method
T max : 223 nm standard value of andrographolides

How to extract from Plant
M.A.E. ( Microwave assisted extraction)

Rapid localized heating of moisture in samples
by microwaves
MAE is process of using Microwaves energy to
heat solvent in contact with sample in order to
partition analytes from the sample matrix into
the sample.
HPLC METHOD for analysis
Weigh about 2.5 gm of andrographis paniculata plant
powder of powder of sample A & B into round
bottom flask added about 50ml methanol and reflux
on water bath for 30 min cool and filter reflux
residue further with methanol till last extract
colorless cool and filter same repeated twice
Preparation of standard solution : By dissolving 10
mg of andragopholides ( 99. 8% ) with 100 ml
methanol give concentration 100 ug/ml.
Cell culture
Human Umbilical vein endothelial cell isolated
from fresh umbilical and veins .
The isolated endothelial cell were culutured in M
199 containing 20% Fetal bovine serum which
heat inactive in 30 ug /ml Endothelial cell growth
supplement 5 u/ ml heaparin and 100 u/ ml
penicillin and 100 ug / ml streptomycin in
humidified atomsphere of 95 % CO 2 at 37c
experiment performed on cell cultures of the third
to sixth passages.
MODE OF ACTION
Androgragrapholides treatment inhibited the in
vitro proliferation of different tumor cell lines it
exerts direct anticancer activity on cancer cell by
cell cycle arrest at G0 / G1 phase through
interaction of cell cycle inhibitory protein P27 and
decrease expression of cyclin dependent kinase 4
It exhibited potent cytotoxic activity against KB (
human epidermal leukemia ) and P 388 (
lymphocytic leukemia ) cell.



Cell diffrentiation in mouse
It inhibit the proliferation of various cell
line including leukemia , breast cancer , lung
cancer, melanoma cells.
PHARMACOKINETICS
It is quickly and compeletly absorbed in the drug
following oral administration 20 mg/ kg. weight in
rats.
Its bioavailabity decreased 4 fold when 10 times
higher dose is used
Large 55% of and is bond to plasma protein and
limited amount can enter the cell
The pharmacokinetics well described by one
compartmental model
Renal excretion is not main route for elimination
It is most like by intensity and dose dependently
metabolised
Oral administration of four tablets ( single therapeutic
dose equivalent to20 mg andrographolides ) to
humans maximum plasma level approximately 393
mg/ ml were reached after 1.5 2 hrs
Using UV diode array detection method Half life &
mean resistance time 6.6 & 10 hrs.
Andrographolides
References -
A novel semi-synthetic andrographolide analogue A5 inhibits tumor
angiogenesis via blocking the VEGFR2-p38/ERK1/2 signal pathway Chenyuan
Gong, Chong Xu, Lili Ji*, Zhengtao Wang The MOE Key Laboratory for
Standardization of Chinese Medicines and The Shanghai Key Laboratory for
Compound Chinese medicines, Institute of Chinese Materia Medica,
Shanghai University of Traditional Chinese Medicine, Shanghai, China.
QUANTITATIVE HPLC ANALYSIS OF ANDROGRAPHOLIDE IN
ANDROGRAPHIS PANICULATA AT TWO DIFFERENT STAGES OF LIFE CYCLE OF
PLANT MEENU SHARMA*, AAKANKSHA SHARMA and SANDEEP TYAGIa
Department of Chemistry, Graphic Era University, DEHRADUN 248001
(Uttarakhand) INDIA aWindlass Biotech, DEHARADUN 248001 (Uttarakhand)
INDIA