PLATELET-AGGREGATION INHIBITOR FROM MURRAYA-EUCHRESTIFOLIA

Twenty-three carbazole alkaloids, murrayafoline-A (1), 3-methyl-carbaz ole (2), murrayanine (3), mukoeic acid (4), murrayazolidine (5), bicyc lomahanimbine (6), murrayamine-A (10), -D (13), -E (14), -F (15), -I ( 16), -J (17), -K (18), -M (7), -N (19), murrayazoline (8), girinimbine (9), mahanimbine (11), (+)-mahanine (12), isomahanine (20), murrafoli ne-A (21), -B (22) and bismurrayafoline-A (23) and a triterpenoid, fri edelin together with p-sitosterol were isolated and characterized from the leaves and root bark of M. euchrestifolia. Their structures were elucidated by spectroscopic analyses and/or direct comparison with aut hentic samples. The isolated carbazole alkaloids 1-12 were subjected t o evaluation for antiplatelet aggregation activity and vasorelaxing ef fect. Most of the isolated carbazole alkaloids showed potent inhibitor y, activity on rabbit platelet aggregation induced by arachidonic acid (100 mu M), collagen (10 mu g/mL) and PAF (2 ng/mL). Only murrayafoli ne-A (1) showed inhibition of tonic contraction induced by K+ (80 mM) + Ca2+ (1.9 mM). Compounds 1, 7 and 12 showed the promotion of the pla telet aggregation or lysis at high dose. In contrast, they also exhibi ted antiplatelet aggregation activity at low concentration. This resul t could continue the philosophy of use in Chinese medicine, in that th e dose variation in a prescription produced different, promotive or in hibitive, effects on therapy. (C) 1998 John Wiley & Sons, Ltd.