Anticancer Activity And pharmacokinetics study of androgopholides

8/12/2019 Anticancer Activity And pharmacokinetics study of androgopholides

1/21

A

SEMINAR ON

Anticancer Activity And pharmacokinetics

study of androgopholides

PRESENTED BY: GUIDED BY:Mr Pravin Dukare Dr V P Choudhari

(M. Pharm Sem - II) HOD

Department of Deparment of Quality

Quality Assurance Assurance Techniques

MAEERS

Maharashtra Institute Of Pharmacy1


2/21

- 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 : -


3/21

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 .


4/21

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


5/21

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


6/21

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


7/21

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


8/21

ANDROGRAPHOLIDES


9/21

Properties -

Molecular formula : C 20 H 30 O 5 Formula weight : 350. 45

Chemical name : 3alpha ,14 ,15, 18tetrahydroxy -

5 Beta, 9 Beta H, 10 alpha

labda

8 ,12 diene

16oic acid , gamma lactone

Physiochemical properties:

Melting point : 231c. Moisture content : By karl fischer method

T max : 223 nm standard value of andrographolides


10/21

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 intothe sample.


11/21


12/21

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.


13/21


14/21

Cell diffrentiation in mouse It inhibit the proliferation of various cell

line including leukemia , breast cancer , lung

cancer, melanoma cells.


15/21

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


16/21

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.


17/21

Andrographolides


18/21

ReferencesI. In-Silico Analysis of Andrographolide against Cancer

R. Sharmila, K. M. Subburathinam, S. Aishwarya, A. Anita Margret1. Department of Biotechnology and Bioinformatics, Bishop Heber College,

Tiruchirappalli-620017, Tamil Nadu, India

2. P.G. and Research Department of Zoology, Rajah Sarfoji College, Thanjavur-

613005, Tamil Nadu, India.

II. Journal of Pharmacognosy and Phytochemistry Vol. 2 No. 1 2013

Optimization of Microwave Assisted Extraction of Andrographolide from

Andrographis paniculata and its Comparison with Refluxation Extraction

Method

Manvitha Mohan, Salma Khanam, B.G. Shivananda

1. Department of Pharmacognosy, East West College of Pharmacy, Bangalore 91,

India.

2. Department of Pharmacognosy, Al-Ameen college of Pharmacy, Bangalore-27,

India


19/21

III. 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

Windlass Biotech, DEHARADUN248001 (Uttarakhand)

INDIA(Received : 15.10.2011; Accepted : 08.11.2011)

IV. A novel semi-synthetic andrographolide analogue A5 inhibits tumorangiogenesis 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 ChineseMedicine, Shanghai, China.


20/21


21/21

Documents

Anticancer Activity And pharmacokinetics study of androgopholides