1 OP
CYTOTOXIC BRUCEOLIDES F R O M- B
.”
JAVANICA
F. A. D a r w i s h , F. J . E v a n s , J . D . P h i l l i p s o n , Department of Pharmacognosy, The S c h o o l of Pharmacy, U n i v e r s i t y of London, 29-39 Rrunswick S q u a r e , London WCIN ;AX
B i t t e r s u b s t a n c e s known a s q u a s s i n o i d s a r e o b t a i n e d f r o m a number of g e n e r a ( e . g . Q u a s s i a ) i n t h e m a i n l y p a n t r o p i c a l f a m i l y Simaroubaceae. The g e n u s B r u c e a , which h a s f o u r species i n A f r i c a and two s p e c i e s i n A s i a (Nooteboom, 7 9 6 2 ) c o n t a i n s a t y p e of q u a s s i n o i d which i s b a s e d on t h e p a r e n t p e n t a c y c l i c a l c o h o l bruceolide. The b r u c e o l i d e s a r e a s e r i e s of e s t e r s w h i c h d i f f e r f r o m e a c h o t h e r by t h e n a t u r e of t h e i r e s t e r i f y i n g a c i d s . A number of b r u c e o l i d e s , i n c l u d i n g b r u c e a n t i n and b r u c e a n t i n o l i s o l a t e d from B. a n t i d y s e n t e r i c a , have s i g n i f i c a n t i n h i b i t o r y a c t i v i t i e s a g a i n s t e x p e r i m e n t a l tumour s y s t e m s s u c h a s t h e i n v i t r o 9-KB s y s t e m and t h e i n v i v o P 388 leukemia (Kupchan e t a 1 1 9 7 3 and 1975).
I n v i e w of t h e w i d e s p r e a d d i s t r i b u t i o n of Brucea s p e c i e s and t h e p o s s i b l e e x i s t e n c e of d i f f e r e n t c h e m i c a l s t r a i n s , & j a v a n i c a ( L . ) M e r r . ( s y n . B. a m a r i s s i m a Desv. e x Gomes, B. s u m a t r a n a Roxb. ) A o b t a i n e d from F i j i h a s been r e - i n v e s t i g a t e F f o r b r u c e o l i d e s . c y t o t o x i c i t y t e s t u s i n g TLX-5 mice lymphoma c e l l s h a s b e e n d e v e l o p e d f o r e v a l u a t i n g p l a n t e x t r a c t s , and h a s b e e n a p p l i e d a s a n a i d t o t h e s e p a r a t i o n of t h e b r u c e o l i d e s ( P h i l l i p s o n and D a r w i s h , 1979). The major b r u c e o l i d e of t h e r o o t s and f r u i t s was i d e n t i f i e d a s b r u c e i n e A ( c h a r a c t e r i z e d b y PMR and MS) and was shown t o have a n I D of 0.031kg I m l i n t h e TLX-5 mouse lymphom 50 test. The n o v e l b r u c e o l i d e , d e h y d r o b r u c e i n e A w a s a l s o i s o l a t e d and i t s s t r u c t u r e , which was deduced f r o m i t s PMR and MS p r o p e r t i e s , was c o n f i r m e d by c o n v e r s i o n of b r u c e i n e A t o d e h y d r o b r u c e i n e A. The n a t u r a l p r o d u c t p r o v e d t o be i d e n t i c a l (TLC, MS) w i t h t h e p r e p a r e d compound. B r u c e a n t i n and b r u c e a n t a r i n , which h a v e n o t p r e v i o u s l y b e e n r e p o r t e d f r o m B. j a v a n i c a , w e r e 31-50 i s o l a t e d t o g e t h e r w i t h b r u c e i n e B , b r u c e i n e C and d e h y d r o b r u c e i n e B which have been p r e v i o u d - y r e p o r t e d from t h i s p l a n t ( Polonsky, 1973)
.
Kupchan, S.M., B r i t t o n , R.W. e t a 1 ( 1 9 7 3 ) J . Org. Chem. 38: 178-1 79 4 0 : 648-654 Kupchan, S.M., B r i t t o n , R.W. e t a 1 ( 1 9 7 5 ) I b i d . Nooteboom, H . P . ( 1 9 6 2 ) F l o r a M a l e s i a n a , S e r i e s I , 6 : 193-226 P h i l l i p s o n , J . D . , D a r w i s h , F . D . ( 1 9 7 9 ) P l a n t a Medica 35: 308-31 5 P o l o n s k y , J . ( 1 9 7 3 ) P r o g r e s s i n t h e C h e m i s t r y of O r g a n i c N a t u r a l Products 30 :I 02-1 50
CYTOTOXIC BRUCEOLIDES F R O M- B
.”
JAVANICA
F. A. D a r w i s h , F. J . E v a n s , J . D . P h i l l i p s o n , Department of Pharmacognosy, The S c h o o l of Pharmacy, U n i v e r s i t y of London, 29-39 Rrunswick S q u a r e , London WCIN ;AX
B i t t e r s u b s t a n c e s known a s q u a s s i n o i d s a r e o b t a i n e d f r o m a number of g e n e r a ( e . g . Q u a s s i a ) i n t h e m a i n l y p a n t r o p i c a l f a m i l y Simaroubaceae. The g e n u s B r u c e a , which h a s f o u r species i n A f r i c a and two s p e c i e s i n A s i a (Nooteboom, 7 9 6 2 ) c o n t a i n s a t y p e of q u a s s i n o i d which i s b a s e d on t h e p a r e n t p e n t a c y c l i c a l c o h o l bruceolide. The b r u c e o l i d e s a r e a s e r i e s of e s t e r s w h i c h d i f f e r f r o m e a c h o t h e r by t h e n a t u r e of t h e i r e s t e r i f y i n g a c i d s . A number of b r u c e o l i d e s , i n c l u d i n g b r u c e a n t i n and b r u c e a n t i n o l i s o l a t e d from B. a n t i d y s e n t e r i c a , have s i g n i f i c a n t i n h i b i t o r y a c t i v i t i e s a g a i n s t e x p e r i m e n t a l tumour s y s t e m s s u c h a s t h e i n v i t r o 9-KB s y s t e m and t h e i n v i v o P 388 leukemia (Kupchan e t a 1 1 9 7 3 and 1975).
I n v i e w of t h e w i d e s p r e a d d i s t r i b u t i o n of Brucea s p e c i e s and t h e p o s s i b l e e x i s t e n c e of d i f f e r e n t c h e m i c a l s t r a i n s , & j a v a n i c a ( L . ) M e r r . ( s y n . B. a m a r i s s i m a Desv. e x Gomes, B. s u m a t r a n a Roxb. ) A o b t a i n e d from F i j i h a s been r e - i n v e s t i g a t e F f o r b r u c e o l i d e s . c y t o t o x i c i t y t e s t u s i n g TLX-5 mice lymphoma c e l l s h a s b e e n d e v e l o p e d f o r e v a l u a t i n g p l a n t e x t r a c t s , and h a s b e e n a p p l i e d a s a n a i d t o t h e s e p a r a t i o n of t h e b r u c e o l i d e s ( P h i l l i p s o n and D a r w i s h , 1979). The major b r u c e o l i d e of t h e r o o t s and f r u i t s was i d e n t i f i e d a s b r u c e i n e A ( c h a r a c t e r i z e d b y PMR and MS) and was shown t o have a n I D of 0.031kg I m l i n t h e TLX-5 mouse lymphom 50 test. The n o v e l b r u c e o l i d e , d e h y d r o b r u c e i n e A w a s a l s o i s o l a t e d and i t s s t r u c t u r e , which was deduced f r o m i t s PMR and MS p r o p e r t i e s , was c o n f i r m e d by c o n v e r s i o n of b r u c e i n e A t o d e h y d r o b r u c e i n e A. The n a t u r a l p r o d u c t p r o v e d t o be i d e n t i c a l (TLC, MS) w i t h t h e p r e p a r e d compound. B r u c e a n t i n and b r u c e a n t a r i n , which h a v e n o t p r e v i o u s l y b e e n r e p o r t e d f r o m B. j a v a n i c a , w e r e 31-50 i s o l a t e d t o g e t h e r w i t h b r u c e i n e B , b r u c e i n e C and d e h y d r o b r u c e i n e B which have been p r e v i o u d - y r e p o r t e d from t h i s p l a n t ( Polonsky, 1973)
.
Kupchan, S.M., B r i t t o n , R.W. e t a 1 ( 1 9 7 3 ) J . Org. Chem. 38: 178-1 79 4 0 : 648-654 Kupchan, S.M., B r i t t o n , R.W. e t a 1 ( 1 9 7 5 ) I b i d . Nooteboom, H . P . ( 1 9 6 2 ) F l o r a M a l e s i a n a , S e r i e s I , 6 : 193-226 P h i l l i p s o n , J . D . , D a r w i s h , F . D . ( 1 9 7 9 ) P l a n t a Medica 35: 308-31 5 P o l o n s k y , J . ( 1 9 7 3 ) P r o g r e s s i n t h e C h e m i s t r y of O r g a n i c N a t u r a l Products 30 :I 02-1 50
