Selective antileishmania activity of 13,28‐epoxy‐oleanane and related triterpene saponins from the plant families Myrsinaceae,Primulaceae, Aceraceae and Icacinaceae

Maesa saponins with the 13,28‐epoxy‐oleanane triterpene core skeleton were described recently to possess strong and selective in vitro and in vivo antileishmania activity. In the absence of direct chemical derivatization possibilities, a structure‐based literature search was carried out to explore a structure‐activity relationship. Crude alcohol extracts from several plant species of Myrsinaceae, Primulaceae, Aceraceae and Icacinaceae were evaluated for in vitro activity against Leishmania infantum intracellular amastigotes and cytotoxicity on MRC‐5_SV2 cells, while the saponin content was evaluated qualitatively by TLC. A clear correlation was found between the presence of close analogue 13,28‐epoxy‐oleanane triterpene saponins and potent and selective antileishmania activity. This was most striking in Maesa species, except for M. macrosepala. Interesting activities were also found in extracts that did not exactly match the TLC characteristics of the Maesa saponin references, as was the case for Ardisia angusta, A. amherstiana, A. caudata, A. gigantifolia, A. roseiflora, Myrsine affinis, Acer brevipes and A. laurinum var. petelotii. This study indicates that the 13,28‐epoxy‐oleanane triterpene moiety is essential for selective antileishmania potential and that several other plant species could still be explored for antileishmania drug discovery. Copyright © 2009 John Wiley & Sons, Ltd.     

齐墩果烷三萜类化合物的抗肿瘤活性及机制研究进展

齐墩果烷三萜类化合物具有广泛的生物活性,其中包括抗肿瘤活性。近年来的研究显示,该类化合物对肿瘤细胞的促凋亡作用与肿瘤细胞线粒体途径的激活密切相关。介绍了齐墩果烷三萜类化合物的抗肿瘤活性,以及该类化合物激活肿瘤细胞凋亡线粒体途径的机制,为进一步探究该类化合物的作用机制及相关药物研发提供参考。     

藏药亚吉玛(长梗金腰)醋酸乙酯部位的化学成分研究

目的研究藏药亚吉玛(长梗金腰Chrysosplenium axillare)醋酸乙酯部位的化学成分。方法采用HP-20大孔吸附树脂、Sephadex LH-20凝胶等柱色谱以及制备高效液相技术进行化学成分分离,采用NMR和HR-ESI-MS等光谱方法进行化合物结构鉴定。结果分离得到17个高度氧化的黄酮醇衍生物及4个三萜类化合物,其结构分别鉴定为5,6,4’-三羟基-3,7,3’-三甲氧基黄酮-6-O-β-D-葡萄糖苷(1)、5,6,3’-三羟基-3,7,4’-三甲氧基黄酮-6-O-β-D-葡萄糖苷(2)、chrysosplenoside H(3)、5-O-demethylapulein (4)、5,3’-二羟基-3,6,7,4’-四甲氧基黄酮(5)、5,2’-二羟基-3,7,4’,5’-四甲氧基黄酮(6)、chrysosplenol C (7)、5,2’,5’-三羟基-3,7,4’-三甲氧基黄酮(8)、axillarin (9)、brickellin (10)、槲皮素(11)、芦丁(12)、isorientin (13)、chrysosplenosideE (14)、槲皮素3-O-β-...     

基于UFLC-Q-TOF/MS技术的八月札化学成分研究

目的 采用快速液相与四极杆飞行时间串联质谱（UFLC-Q-TOF/MS）联用技术分析鉴定八月札Akebiae Fructus的化学成分。方法 采用Acquity UPLC BEH C₁₈（100 mm×2.1 mm,1.7 μm）色谱柱,以0.1%甲酸-乙腈和0.1%甲酸-水为流动相进行快速梯度洗脱,体积流量0.3 mL/min,柱温40 ℃,进样量1 μL。质谱定性采用电喷雾离子源（ESI）的飞行时间质谱,负离子模式下采集数据,全扫描的质量扫描范围m/z 100～1 500。结果 依据质谱裂解规律,从八月札的甲醇提取物中共鉴定出25个三萜类成分,并对另外9个未知成分进行了结构推测。结论 UFLC-Q-TOF/MS方法能够快速、准确、全面地鉴定八月札中的多种成分,为八月札的进一步提取分离和药理作用机制研究提供依据。     

玉蕊醇型三萜的结构特征、波谱规律及药理活性研究进展

玉蕊醇型三萜是在多科植物中广泛存在的具有多羟基取代的齐墩果烷型三萜类成分。由于多羟基基团的存在,在植物次生代谢过程中,导致这类成分广泛存在不同种类酰基和糖的取代,使得玉蕊醇型三萜类化合物具有多种生物活性。玉蕊醇型三萜具有显著的抗肿瘤及改善学习记忆等作用,其在治疗肿瘤及老年退行性疾病如阿尔茨海默病方面具有极大的开发应用前景。结合文献对玉蕊醇型三萜的结构特征、波谱规律和药理活性等方面进行详细的总结,为这类化学成分的开发及应用提供重要的基础。     

天然五环三萜及其衍生物抗心脑血管疾病的研究进展

心脑血管疾病是我国成年人群首要致死病因,且发病率呈上升和年轻化趋势,运用中药治疗心脑血管疾病十分必要。天然产物是治疗心脑血管药物的重要来源。三萜类化合物是植物体内重要的次生代谢产物,具有广泛的生物活性,其中五环三萜类表现出明显的抗炎、抗肿瘤、抗病毒等药理作用。近年来,越来越多的研究集中在五环三萜类化合物抗心脑血管疾病领域,对其结构进行衍生化从而提升活性、改善药性的研究也越发深入。通过查阅国内外五环三萜类化合物及其衍生物近10年的文献专利报道,综述了齐墩果烷、乌苏烷、羽扇豆烷、木栓烷4种类型五环三萜类化合物及其衍生物抗心脑血管疾病的研究进展,为治疗心脑血管疾病药物的研发提供依据和参考。     

Oleanane derivatives for pharmaceutical use: a patent review (2000-2016)

Introduction: Oleanolic acid has been considered a good start molecule for synthetic exploitation. Thus hundreds of oleanane triterpenoids have been synthesized and patented.

Also many oleanane saponins have been patented for their biological activities and possible pharmaceutical use.

Areas covered: Patents reporting the biological activities of oleanane derivatives and saponins with oleanane-type aglycones were examined. Among the synthesized oleanane derivatives, the most promising seem to be 2-cyano-3,12-dioxoolean-1,9(11)-dien-28-oic acid derivatives which interfere with many pathways involved in inflammation, oxidative stress and cell proliferation. Regarding oleanane-type saponins, several patents claiming their antiproliferative activity or their possible use as adjuvants in vaccines, were reported.

Expert opinion: Despite the great number of synthesized oleanane triterpenoids, only CDDO-Me entered clinical development as a possible drug for the treatment of chronic kidney disease (CKD) but a phase 3 clinical trial was terminated due to heart-related adverse effects. Further phase 2 clinical trials of CDDO-Me are in progress for the treatment of CKD and PAH (pulmonary arterial hypertension) patients without heart-related risk factors. Additional investigations leading to compounds with an improved activity/toxicity profile along with well-designed preclinical and clinical trials are needed. Regarding oleanane-type saponins, the real perspective seems to be as adjuvants in vaccines.     

黔产细锥香茶菜中化学成分的研究

目的研究黔产细锥香茶菜Isodon coetsa的化学成分。方法采用硅胶、凝胶柱色谱、制备型HPLC等方法进行分离纯化,通过理化性质、光谱数据结合参考文献鉴定化合物结构。结果从细锥香茶菜95%甲醇提取物中分离得到了19个化合物,分别鉴定为β-谷甾醇(1)、豆甾醇(2)、β-胡萝卜苷(3)、亚麻酸甲酯(4)、油酸-1,3-甘油二酯(5)、熊果酸(6)、齐墩果酸(7)、3β-羟基-乌索-20-烯-28-酸(8)、白桦脂酸(9)、苦参黄素(10)、山楂酸(11)、2α羟基-熊果酸(12)、2α,3α-二羟基-12-烯-28-乌苏酸(13)、2α,3α,24-三羟基-12-烯-28-齐墩果酸(14)、2α,3α,24-三羟基-12-烯-28-熊果酸(15)、芒柄花素(16)、大黄素(17)、尿嘧啶(18)、蔗糖(19)。结论化合物2、4、5、9、11、13~19均为首次从该植物中分离得到,化合物11、17、19为首次从香茶菜属植物中分离得到。     

人参皂苷生物合成相关的尿苷二磷酸依赖的糖基转移酶研究进展

人参皂苷是一类具有丰富药理活性的重要天然产物,常见的类型包括达玛烷型（protopanaxadiol type,PPD-type/proto-panaxatriol type,PPT-type）、齐墩果烷型（oleanane type,OA-type）和奥克悌隆型（ocotillol type,OCT-type）,可广泛应用于医药、农业和工业生产等领域。尿苷二磷酸（Uridine diphosphate,UDP）依赖的糖基转移酶（UDP-glycosyltransferases,UGTs）是催化人参皂苷生成的关键酶,对人参皂苷结构的形成及药理作用的发挥具有重要意义。综述了人参皂苷的分布、结构多样性和生物合成途径,并基于几种常见人参皂苷类型重点阐述了与糖基化反应相关的UGTs,以期为人参皂苷生物合成相关研究提供参考。