Characterisation and antimalarial activities of metabolites from leaves of

Anonidium mannii

ByGP Makoni

Supervisor: Prof RW Krause

42nd Annual SACI Conference 2015 KZN

2 December 2015

Malaria: The case

2

Malaria: Drug target area

3

Bioassays• Antimalarial• Cytotoxicity• Microbial

Evaluate• Active secondary

metabolites in Anonidium mannii

Identify

• New drugs• Scaffolds

Add value

• Ethno-medicinal uses

Validate

Objectives of

Research

4

Anonidium mannii• Belongs to the Annonaceae

family and is native to Cameroon.

• Ethno medicinal uses include:

1. Malaria

2. Gonorrhoea

3. Dysentery

4. Cancer

5. Skin inflammation5

MethodologySolvent extraction

1:1 DCM: MeOH

VLCGradient elution

CCActive fractions

AntimalarialCell cytotoxicity &

anticancer

Microbial assays

Bioassay

6

Structure elucidation

2D NMR

1D NMR

MS

FTIR

MP

CHNS

COSY

HSQC HMBC

NOESY

1H NMR

13CNMR

DEPT135Structure

elucidation

77

Results%

via

bilit

y

Cytotoxicity and pLDH comparison

8

pLDH

Cell cytotoxicity

Suggested structures

AM1C yield 1.94% or 0.09% AM2C 1.06% & 0.05%

AM3C 0.33% &0.02%9

HO

OH

12

34

56

7

8109

11

14

13

15

16

1712

18

19 20 22

2421

27

26

25

23

HO

OH

12

34

56

7

8109

11

14

13

15

16

1712

18

19 20 2224

26

27

28

29

30

2325

21

12

34

56

7

89

10

11

1213

14 15

16

1718

1920

21

22

23

24

25

26

29

30

31

27

28

32

33

HO

AM1C 1HNMR

10

HO

OH

12

34

56

7

8109

11

14

13

15

16

1712

18

19 20 2224

26

27

28

29

30

2325

21

AM1C 13CNMR

11

HO

OH

12

34

56

7

8109

11

14

13

15

16

1712

18

19 20 2224

26

27

28

29

30

2325

21

AM1C COSY

12

H20

H20

H21

H21

HO

OH

12

34

56

7

8109

11

14

13

15

16

1712

18

19 20 2224

26

27

28

29

30

2325

21

AM1C HMBC

C9

H7H14

H12 H18

HO

OH

12

34

56

7

8109

11

14

13

15

16

1712

18

19 20 2224

26

27

28

29

30

2325

21

13

Conclusion & comments

• Antimalarial screening has shown that there are metabolites in Anonidium mannii that are active against malaria.

• Work is still in progress to further investigate the cytotoxic fraction for their anti-cancer activities.

• Structural elucidation is still in progress for the other pure metabolites extracted.

• SAR & absolute configuration are still under consideration.

14

Acknowledgements

• My supervisor: Prof. R Krause

• Dr X Siwe Noundou

• Rhodes University Chemistry Dept

• Rhodes Sandisa Imbewu Fund

THANK YOU