a seminar on anticancer and pharmacokinetics study on andrographolides

8/12/2019 A SEMINAR ON ANTICANCER AND PHARMACOKINETICS STUDY ON ANDROGRAPHOLIDES

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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


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- Uncontrolled growth of abnormal cell

- Most serious disease

- Extensive research is done all over the worldstructure based drug designing offers

computational approach to identify the potential

leads which can be developed into a drug

Cancer : -


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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 daughtercells 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 susceptibilityand 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 .


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ANTICANCER DRUGS1. Alkylating agents-

cyclophosphamide+busulphal+chlorambucil2. Antimetabolites- methotrexate+6-

thioguanine+flourouracil

3. Antibiotics- doxorubiciln+dleomycil+actinomycil4. Enzymes- L-asparaginase

5. Vinca AlkaloidesVincristine+vinblastine

6. Hormones- glucocorticoids+progestins+estramustine

7. Miscellaneous-Hydroyurea+ procarbazine+ cisplatin

8. Monoclonal antibodies


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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


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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


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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


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ANDROGRAPHOLIDES


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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 refluxresidue further with methanol till last extract

colorless cool and filter same repeated twice

Preparation of standard solution : By dissolving 10mg of andragopholides ( 99. 8% ) with 100 ml

methanol give concentration 100 ug/ml.


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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 inhumidified atomsphere of 95 % CO 2 at 37c

experiment performed on cell cultures of the third

to sixth passages.


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MODE OF ACTION

Androgragrapholides treatment inhibited the in

vitro proliferation of different tumor cell lines it

exerts direct anticancer activity on cancer cell bycell 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.


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Cell diffrentiation in mouse It inhibit the proliferation of various cell

line including leukemia , breast cancer , lung

cancer, melanoma cells.


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PHARMACOKINETICS

It is quickly and compeletly absorbed in the drugfollowing 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 onecompartmental model


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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 UVdiode array detection method Half life &

mean resistance time 6.6 & 10 hrs.


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Andrographolides


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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, DEHARADUN248001 (Uttarakhand)

INDIA

a seminar on anticancer and pharmacokinetics study on andrographolides

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