Studies on the Chemical Constituents and their Biological

• Main Authors: Chen, Jih-Jung, 陳日榮
• Other Authors: Chen Ih-Sheng
• Format: Others
• Language: zh-TW
• Published: 1997
• Online Access: http://ndltd.ncl.edu.tw/handle/16430938200568733839

博士 === 高雄醫學院 === 藥學研究所 === 85 === As a series of studies on the chemical constituents and biological activities of Formosan plants, the trunk bark of Hernandia nymphaeifolia (Presl) Kubitzki collected in Green Island was investigated. Seventy-four compounds including thirty-two natural new compounds have been isolated. These new compounds were twenty-four aporphine alkaloids, 7-formyldehydroovigerine (77), 7-formyldehydronornantenine (78), 7-formyldehydrohernangerine (79), sonodione (80), demethylsonodione (81), norsonodione (82), oxohernagine (83), oxohernangerine (84), hernanymphine (85), nymphaedonine (86), oxo-O-methylbulbocapnine (87), N-hydroxyovigerine (88), N- hydroxyhernangerine (89), N-formylovigerine (90), N- formylhernangerine (91), N-formyldehydroovigerine (92), N-(N- methylcarbamoyl)-O-methylbulbocapnine (93), dehydrohernandaline (94), oxohernandaline (95), 4-methoxyoxohernandaline (96), ovigeridimerine (97), oviisocorydine (98), ovihernangerine (99) and (+)-laetine (100); three lignans, (-)-6''-hydroxyyatein (101), (-)-hernone (102) and (-)-nymphone (103); one phthalimide alkaloid, 5,6-dimethoxy-N-methylphthalimide (104); one isoquinoline alkaloid, 7-hydroxy-6-methoxy-1-methylisoquinoline (105); one bis-benzylisoquinoline alkaloid, (+)-vateamine-2''-b- N-oxide (106); one dimeric benzylisoquinoline-benzaldehyde alkaloid, (+)-nymphaedaline (107) and one dialdehyde, hernandial (108). In addition, twenty known compounds were first isolated from Hernandia genus and they were four aporphine alkaloids, atheroline (109), magnoflorine (110), corytuberine (111) and N- formylnornantenine (112); one proaporphine alkaloid, (-)-glaziovine (113); four isoquinolone alkaloids, corydaldine (114), N-methylcorydaldine (115), thalifoline (116) and northalifoline (117); one isoquinoline alkaloid, backebergine (118); six steroids, b-sitostenone (119), stigmasta-4,22-dien-3- one (120), 3b-hydroxy-stigmast-5-en-7-one (121), 3b- hydroxystigmasta-5,22-dien-7-one (122), 6a-hydroxystigmast-4- en-3-one (123) and 6a-hydroxystigmasta-4,22-dien-3-one (124); one acetophenone, 3,6-dihydroxy-2-methoxy-4-methylacetophenone (125); two cyclohex-2-en-1-ones, blumenol A (126) and (+)-dehydrovomifoliol (127); and one benzaldehyde, isovanillin (128). Twenty-two known compounds which had been isolated from Hernandia genus including (-)-desoxypodophyllotoxin (1), thalicarpine (3), ovigerine (5), hernangerine (6), reticuline (7), N-methylhernangerine (8), hernovine (9), N-methylovigerine (10), isocorydine (11), laurotetanine (12), N-methyl-6,7- dimethoxyisoquinolone (13), hernandaline (14), N- methyllaurotetanine (18), hernandonine (20), epiaschantin (23), epimagnolin (24), isoboldine (36), N-methylhernovine (49), (+)-malekulatine (52), (-)-yatein (54), epiyangambin (55) and (-)-5''-methoxypodorhizol (57) were again isolated from H. nymphaeifolia. The structures of these compounds were elucidated by spectral analyses or chemical methods. Bioactivity-guided fractionation and chromatography led to the isolation of many active constituents with antiplatelet, vasorelaxing, cytotoxic or antioxidant effect, respectively. Seventeen compounds (1, 3, 5~8, 12, 14, 23, 24, 52, 54, 55, 83, 102, 106, 128) showed significant inhibitory activities on platelet aggregation induced by arachidonic acid, collagen or PAF; among them, (+)-malekulatine (52) [IC50 = 24.8 mM, against AA], (+)-vateamine-2''-b-N-oxide (106) [IC50 = 21.1 mM, against collagn], (+)-epiaschantin (23) [IC50 = 5.9 mM, against PAF], (+)-epimagnolin (24) [IC50 = 7.5 mM, against PAF] and (+)-epiyangambin (55) [IC50 = 6.7 mM, against PAF] were the potentest compounds. Sixteen compounds (3, 5, 6, 8, 12, 14, 18, 23, 24, 52, 54, 83, 84, 103, 106, 116) showed effective inhibitory activities on contraction of vascular smooth muscles by high K+ (80 mM) or norepinephrine (3 mM); among them, ovigerine (5) [IC50 = 12 mM, against K+], N-methyllaurotetanine (18) [IC50 = 16.4 mM, against NE (phasic)] and hernandaline (14) [IC50 = 19.8 mM, against NE (tonic)] showed the potentest vasorelaxing actions. On the other hand, thirteen compounds [1, 5, 10, 20, 54, 81, 85, 86, 92, 96, (mixture of 119 & 120) and 127] showed significant cytotoxic activities (ED50 values < 1 mg/ml) against P-388, KB16, A549 and HT-29 cell lines, in vitro; among them, (-)-desoxypodophyllotoxin (1) [ED50 < 0.003 mM, against 4 cell lines], hernandonine (20) [ED50 < 0.003 mM, against P-388] and (-)-yatein (54) [ED50 < 0.013 mM, against 4 cell lines] showed the strongest cytotoxicities. In addition, eight compounds (6, 7, 8, 9, 12, 52, 83 and 106) showed effective antioxidant activities in scavenging stable free radical, diphenyl-picryl-hydrazyl (DPPH); among them, reticuline (7) [IC0.200 = 2.1 mM], (+)-malekulatine (52) [IC0.200 = 3 mM] and (+)-vateamine-2''-b-N-oxide (106) [IC0.200 = 3 mM] were the potentest antioxidants.