new antiplasmodial alkaloids from stephania rotunda lour. () sothavireak bory 1, sok siya bun 2,...

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New antiplasmodial alkaloids from Stephania rotunda Lour. (កកកកកកកកកក) Sothavireak BORY 1 , Sok Siya BUN 2 , Béatrice BAGHDIKIAN 2 , Valérie MAHIOU 2 , Nadine AZAS 2 , Hot BUN 2 , Evelyne OLLIVIER 2 . 1 Faculty of Pharmacy, University of Health Sciences-Cambodia. 2 UMR-MD3, Faculty of Pharmacy, Aix-Marseille University, France Symposium on Biodiversity and Health 17-18 November 2014

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Page 1: New antiplasmodial alkaloids from Stephania rotunda Lour. () Sothavireak BORY 1, Sok Siya BUN 2, Béatrice BAGHDIKIAN 2, Valérie MAHIOU 2, Nadine AZAS 2,

New antiplasmodial alkaloids from

Stephania rotunda Lour. (កុ�មារពេ�ជ្រ�)

Sothavireak BORY1, Sok Siya BUN2, Béatrice BAGHDIKIAN2,

Valérie MAHIOU2, Nadine AZAS2, Hot BUN2, Evelyne OLLIVIER2.

1 Faculty of Pharmacy, University of Health Sciences-Cambodia.

2 UMR-MD3, Faculty of Pharmacy, Aix-Marseille University, France

Symposium on Biodiversity and Health

17-18 November 2014

Page 2: New antiplasmodial alkaloids from Stephania rotunda Lour. () Sothavireak BORY 1, Sok Siya BUN 2, Béatrice BAGHDIKIAN 2, Valérie MAHIOU 2, Nadine AZAS 2,

2

INTRODUCTION

30 medicinal plants

suspected of

antiplasmodial activity

Symposium on Biodiversity and Health

17-18 November 2014

Page 3: New antiplasmodial alkaloids from Stephania rotunda Lour. () Sothavireak BORY 1, Sok Siya BUN 2, Béatrice BAGHDIKIAN 2, Valérie MAHIOU 2, Nadine AZAS 2,

3

INTRODUCTION

Stephania rotunda Lour.

ពេកុ�មារពេ�ជ្រ�

Extract of tuber:

IC50 < 5 µg/mL

Stephania rotunda presents the most interesting antiplasmodial activity.

Symposium on Biodiversity and Health

17-18 November 2014

Page 4: New antiplasmodial alkaloids from Stephania rotunda Lour. () Sothavireak BORY 1, Sok Siya BUN 2, Béatrice BAGHDIKIAN 2, Valérie MAHIOU 2, Nadine AZAS 2,

4

OBJECTIVES

Isolation and identification of the unknown alkaloids observed

on HPLC chromatograms for the different extracts,

Evaluation of the antiplasmodial activity of alkaloids from the

extracts of Stephania rotunda.

min0 5 10 15 20 25 30 35

mAU

0

25

50

75

100

125

150

175

DAD1 A, Sig=282,4 Ref=360,100 (STEPH\080109000001.D)

8.7

58

11

.48

4

15

.39

7

17

.38

5

24

.71

2

28

.21

4

31

.07

6

36

.53

0

min0 5 10 15 20 25 30 35

mAU

0

10

20

30

40

50

DAD1 A, Sig=282,4 Ref=360,100 (STEPH\080110000000.D)

2.5

86

4.7

46

8.0

89

10

.16

0

13

.09

6

15

.70

2

17

.31

8

20

.06

4

24

.76

5 28

.30

5

Symposium on Biodiversity and Health

17-18 November 2014

Page 5: New antiplasmodial alkaloids from Stephania rotunda Lour. () Sothavireak BORY 1, Sok Siya BUN 2, Béatrice BAGHDIKIAN 2, Valérie MAHIOU 2, Nadine AZAS 2,

5

MATERIALS AND METHODS Plant material

Intrumentation

HPLC FC MS NMR

Phytochemistry:

Antiplasmodial activity: W2 Strain of Plasmodium falciparum

- IC50

- SI

Plants preparation

Herbarium specimens

Plants powder

Symposium on Biodiversity and Health

17-18 November 2014

Page 6: New antiplasmodial alkaloids from Stephania rotunda Lour. () Sothavireak BORY 1, Sok Siya BUN 2, Béatrice BAGHDIKIAN 2, Valérie MAHIOU 2, Nadine AZAS 2,

RESULTS & DISCUSSION

6

Phytochimical study: HPLC, MS, 1D and 2D NMR

N

OCH3

OCH3

O

O

O NCH3

HCH3

H

ONH3CO

H3CO

OCH3

OCH3

N

H3CO

H3CO

OCH3

OCH3

Cepharanthine

Xylopinine Tetrahydropalmatine

min0 5 10 15 20 25 30 35

mAU

0

10

20

30

40

50

DAD1 A, Sig=282,4 Ref=360,100 (STEPH\080110000000.D)

2.5

86

4.7

46

8.0

89

10

.16

0

13

.09

6

15

.70

2

17

.31

8

20

.06

4

24

.76

5

28

.30

5

NCH3

O

O

Roemerine

N+

H3CO

H3CO

OCH3

OCH3

Pseudopalmatine

Palmatine

Symposium on Biodiversity and Health

17-18 November 2014

Page 7: New antiplasmodial alkaloids from Stephania rotunda Lour. () Sothavireak BORY 1, Sok Siya BUN 2, Béatrice BAGHDIKIAN 2, Valérie MAHIOU 2, Nadine AZAS 2,

7

RESULTS & DISCUSSION

Phytochimical study: HPLC, MS, 1D and 2D NMR

NCH3

O

O

OCH3

H3CO

NCH3

O

O

OCH3

Stephanine

min0 5 10 15 20 25 30 35

mAU

0

25

50

75

100

125

150

175

DAD1 A, Sig=282,4 Ref=360,100 (STEPH\080109000001.D)

8.7

58

11

.48

4

15

.39

7

17

.38

5

24

.71

2

28

.21

4

31

.07

6

36

.53

0

Vireakine

Symposium on Biodiversity and Health

17-18 November 2014

Page 8: New antiplasmodial alkaloids from Stephania rotunda Lour. () Sothavireak BORY 1, Sok Siya BUN 2, Béatrice BAGHDIKIAN 2, Valérie MAHIOU 2, Nadine AZAS 2,

RESULTS & DISCUSSION

In vitro antiplasmodial activity

8Symposium on Biodiversity and Health

17-18 November 2014

Page 9: New antiplasmodial alkaloids from Stephania rotunda Lour. () Sothavireak BORY 1, Sok Siya BUN 2, Béatrice BAGHDIKIAN 2, Valérie MAHIOU 2, Nadine AZAS 2,

RESULTS & DISCUSSION

9Symposium on Biodiversity and Health

17-18 November 2014

C X T P CHL ART

C Additive Additive Synergism Additive

X Additive Synergism

T Additive Synergie Additive Additive Additive

P Additive Antagonism Additive

CHL Synergie Additive Antagonism

ART Additive Additive Additive

X : xylopinine, C : cepharanthine, T : tetrahydropalmatine, P: palmatine,

CHL: chloroquine, ART: artesunate.

In vitro antiplasmodial activity: Isobologram study

Page 10: New antiplasmodial alkaloids from Stephania rotunda Lour. () Sothavireak BORY 1, Sok Siya BUN 2, Béatrice BAGHDIKIAN 2, Valérie MAHIOU 2, Nadine AZAS 2,

CONCLUSION

10

8 major alkaloids have been isolated and identified,

Vireakine is identified as a new compound,

Pseudopalmatine, stephanine and vireakine are described for the first time in the plant.

Phytochemical study:

Pseudopalmatine, cepharanthine, stephanine and vireakine are the most active compounds,

Isobologram: 2 synergistic effects and 1 antagonistic effect,

In vitro antiplasmodial activity:

This results justify the use of Stephania rotunda as

traditional medicine for the treatment of malaria.

Select the most promising drug-candidates for further

investigations.

Symposium on Biodiversity and Health

17-18 November 2014

Page 11: New antiplasmodial alkaloids from Stephania rotunda Lour. () Sothavireak BORY 1, Sok Siya BUN 2, Béatrice BAGHDIKIAN 2, Valérie MAHIOU 2, Nadine AZAS 2,

11

2010

2012

2013

2014

2014

2010

Symposium on Biodiversity and Health

17-18 November 2014

Page 12: New antiplasmodial alkaloids from Stephania rotunda Lour. () Sothavireak BORY 1, Sok Siya BUN 2, Béatrice BAGHDIKIAN 2, Valérie MAHIOU 2, Nadine AZAS 2,

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THANK YOU FOR YOUR ATTENTION

Symposium on Biodiversity and Health

17-18 November 2014