Studies on The Chemical Constituents of Drymaria diandra, Dianthus superbus, and Dianthus superbus var. logicalycinus, and the Synthetic` Dianthramide Alkaloid Analogues, and Their Biological Activities

• Main Authors: Pei-Wen Hsieh, 謝珮文
• Other Authors: Yang-Chang Wu
• Format: Others
• Language: zh-TW
• Published: 2005
• Online Access: http://ndltd.ncl.edu.tw/handle/70194536196718378537

博士 === 高雄醫學大學 === 藥學研究所博士班 === 93 === The aim of this dissertation is building up the data including the isolation, structural elucidation, and bioactivities, eg. antiplatelet aggregation, anti-inflammatory, and cytotoxicities of cyclic peptides from three Formosan Caryophyllaceous plants, Drymaria diandra, Dianthus superbus, and Dianthus superbus var. longicalycinus. Fourty compounds were isolated including two alkaloids, drymaritin (DR-15) and 2’-methoxydianthramide B (DS-A12); five flavonoids, torosaflavone A (DR-26), diandraflavone (DR-31), isovitexin (DR-30), isofurcatain (DR-32), and 7-methoxyisofurcatain (DR-33); nine cyclic peptides, diandrine A~ D (DR-22、23、28、29), dianthin C-F (DS-P3~6), and longicalycinin A (DS-P7); two steroids, spinasterol (DR-21) and spinasterol-β-D-glycoside (DR-27); five triterpenoid saponins, dianthoside A, B, G, H (DS-T1, 2, 7, 8), and vaccaroside A (DS-T22); two norsesquiterpenes, 3-oxo-α-ionol (DR-11) and megastigma-4,7-diene-3,9-dione (DR-12), and the other fifteen misllenous compounds, anemonin (DR-9), hexadecanoic acid (DR-10), methyl 5-hydroxy-4-oxopentanoate (DR-13), glycerol-α-lignocerate (DR-14), p-hydroxybenzoic acid (DR-16), p-hydroxybenaldehyde (DR-17), vallinic acid (DR-18), isovanillin (DR-19), 4-methoxy-benzoic aicd methyl ester (DR-20), cis-p-coumarate (DR-24), 3,4-dihydroxybenzoic acid (DR-25), aurantiamide benzoate (DS-O10), 4-(2-hydroxy-ethyl)-2-methoxy-phenol (DS-O11), vanillin (DS-O12), and 3-(4-hydroxy-3-methoxy-phenyl)-propionic acid methyl ester (DS-O13). The structures of them were elucidated and established on the basis of spectoscopic data and chemical derivates. Among them, twelve compounds are new, and twenty-three ones were firstly derived from these plants. Additionally, compound DR-23 exhibited highly slective inhibitory effect on the platelet aggregation induced by collagen; compound DR-31 showed inhibitory activity to neutrophil superoxide generation stimulated by fMLP. Furthermore, drymaritin exhibited anti-HIV effect with an EC50 value of 2.80 µM and a TI value of 20.6 The dianthramide alkaloids and their analogues, which were isolated from the genus Dianthus, were selected as the targets for the further medicinal chemistry study. Seventy-one compounds were synthesized and screened for their cytotoxicity, antiplatelet activity, antiinflammatory, inhibition of neutrophil elastase release, ICAM-1 expression inhibition, and anti-HCoVs activities. On the basis of these screenings, the SARs of these compounds were established or proposed. The mechanisms of the most potent compounds, DS-R14, DS-R15, DS-R16, DS-R21, DS-R31, and DS-R41 are underinvestiged for the pharmacological mechanism to anti-platelet aggregation, inhibition of neutrophil elastase release, and ICAM-1 expression inhibition, respectively.