胡椒基咪唑盐类化合物的合成及生物活性研究

从胡椒酸出发,通过还原、甲磺酸酯化、偶联和成盐四步反应合成了一系列新型的胡椒基咪唑盐类化合物,其结构经¹HNMR, ¹³CNMR,HRMS以及X射线单晶衍射确定.对合成的新化合物进行了体外抗肿瘤细胞毒活性筛选,结果表明,1-((苯并[d][1,3]二氧杂环戊烯-5-基甲基)-3-(2-萘甲基))-5,6-二甲基-1H-苯并[d]咪唑-3-溴盐(30)具有显著的细胞毒活性,对HL-60、SMMC-7721、A-549、MCF-7和SW-480肿瘤细胞株的活性均优于顺铂(DDP),尤其对HL-60肿瘤细胞株表现出较好的选择性细胞毒活性,其IC₅₀值约为顺铂的7.2倍.进一步研究表明,化合物30具有诱导SMMC-7721细胞株在细胞周期G0/G1期阻滞和细胞凋亡的作用.     

胆木枝叶中一个新的吲哚生物碱类化合物

综合运用多种现代色谱学分离方法对黎药胆木中的化学成分进行了研究,从其枝叶的乙醇提取物中分离得到了4个吲哚生物碱类化合物,采用多种现代波谱技术确定了这些化合物的化学结构,分别鉴定为:nauclofficine(1)、naucleamide A(2)、naucleamide D(3)和latifoliamide A(4).其中化合物1为一个新生物碱,化合物2~4为首次从胆木中分离得到的化合物.化合物1~4的体外细胞毒活性评价结果表明,它们对5种肿瘤细胞株(HL-60、A549、SMMC-7721、MCF-7和SW480)均显示出了较为显著的体外生长抑制活性,细胞毒活性与抗肿瘤阳性对照药顺铂的活性相当.     

毛叶鹰爪花中一个新颖的裂环多氧取代环己烯类化合物

综合运用多种现代色谱学分离方法对毛叶鹰爪花中的化学成分进行了研究,从其枝叶的乙醇提取物中分离得到了3个裂环多氧取代环己烯类化合物,采用多种现代波谱技术确定了这些化合物的化学结构,分别鉴定为artapilosol A(1),microcarpin A(2)和uvarisubol B(3).其中化合物1为一个新化合物,化合物2和3为首次从鹰爪花属植物中分离得到的化合物.化合物1~3的体外细胞毒活性筛选结果表明它们对5种肿瘤细胞株(HL-60,A549,SMMC-7721,MCF-7和SW480)均显示出了较强的体外生长抑制活性,它们的细胞毒活性与抗肿瘤阳性对照药顺铂相当.     

见血封喉根中类黄酮的结构鉴定

从海南产见血封喉[Antiaris toxicaria (Pers.) Lesch.]根的乙醇提取物中分离得到8个黄酮类化合物, 分别鉴定为antiarones K, B, F～I (1～6), (±)-sigmoidin A (7)和2-[2,3-二氢-4-羟基-2-(2-羟基-2-丙基)-5-甲氧基-1H-茚基]-1-(2,4,6-三羟基苯基)乙酮(8). 其中antiarone K (1)为新的异戊烯基二氢黄酮. 运用现代波谱技术, 包括二维核磁共振谱和高分辨质谱, 对上述化合物的结构进行了确证. 以上化合物经滤纸片法进行抗菌活性测试, 结果表明化合物1和3均具有抗金黄色葡萄球菌活性, 化合物3还具有抗耐甲氧西林金黄色葡萄球菌(MRSA)活性; 经MTT法进行细胞毒活性测试, 结果表明化合物1和6～8对慢性髓原白血病细胞(K562)、人胃癌细胞(SGC-7901)和人肝癌细胞(SMMC-7721)的增殖显示了生长抑制活性.     

异叶三宝木枝叶中一个新的Stemodane型二萜类化合物

综合运用硅胶柱色谱、反相硅胶柱色谱、Sephadex LH-20凝胶柱色谱以及制备型高效液相色谱等色谱分离技术对大戟科三宝木属植物异叶三宝木Trigonostemon heterophyllus枝叶中的化学成分进行了系统研究,从其枝叶的85%乙醇提取物中分离得到了8个二萜类化合物.采用多种波谱鉴定技术确定了这些化合物的化学结构.其中一个化合物为新的罕见的stemodane型二萜类化合物,七个化合物为首次从三宝木属植物中分离得到的化合物.所有化合物的体外细胞毒活性评价结果表明,它们对五种肿瘤细胞株(HL-60、A549、SMMC-7721、MCF-7和SW480)均显示出了较为显著的体外生长抑制活性,它们的细胞毒活性与抗肿瘤阳性对照药顺铂的活性相当.     

疣孢菌NS0172产生的邻二烷基取代芳香酸

从疣孢菌NS0172的发酵产物中分离得到2个新的邻二烷基取代芳香酸类化合物1和2.通过一维和二维NMR数据解析及高分辨质谱分析确定了化合物1和2的化学结构.利用噻唑蓝(MTT)比色法测定了化合物1和2的细胞毒活性,结果显示化合物1对人肝癌细胞SMMC-7721具有一定的细胞毒性(IC507.74μmol·L^-1).利用滤纸片法测定了化合物1和2的抗细菌和抗真菌活性,结果显示两者在40μg/disc条件下均无抗菌活性.这是首次报道疣孢菌代谢产生邻二烷基取代芳香酸类化合物,为后续开展相关生物合成机制研究奠定了基础.     

海洋放线菌Streptomyces sp.124092中的细胞毒活性成分

对海洋放线菌Streptomyces sp.发酵液的提取物进行柱层析分离, 得到5个化合物. 经MS, NMR, 1H-1H COSY, HSQC和HMBC等数据鉴定, 其结构分别为3-氨基-丙酸对甲苯酯(1)、6-Amino-3-(4-hydroxybenzyl)-1,4-diazonane-2,5-dione(2)、正丁基-α-D-吡喃甘露糖苷(3)、大豆苷元(4)和1H-3-吲哚甲酸(5). 其中化合物1和2为新化合物, 细胞毒活性测试结果表明, 化合物1~4对人肝癌细胞(SMMC-7721)具有不同程度的生长抑制活性.     

新型18β-甘草次酸氨基二硫代甲酸酯衍生物的合成及抗癌活性研究

以18β-甘草次酸为原料首先经简单酰胺化反应方便地得到18β-甘草次酸哌嗪,再与二硫化碳、碳酸钾以及不同结构卤代烃"一锅煮"法快速、高效地合成了10种含氨基二硫代甲酸酯结构的新型甘草次酸酰胺类衍生物,通过IR,1H NMR,13C NMR和HR-MS对所有新化合物进行了结构确证;并以四甲基偶氮唑盐比色法(MTT)法评价了该类化合物对人肝癌细胞株SMMC-7721的细胞毒活性.初步生物活性研究结果表明,该类化合物具有明显的抑制人肝癌细胞增殖、诱导其凋亡的细胞毒活性,给药72 h,半抑制浓度IC50最优值仅为14.42μg/mL.     

肟醚噻二唑硫醚化合物的合成及其抗肿瘤活性

将2-巯基-5-取代基-1,3,4-噻二唑经与β-氯苯丙酮取代、盐酸羟胺肟化和氯甲基噁二唑醚化,合成了6种3-(5-取代基-1,3,4-噻二唑-2-硫代基)-1-苯基丙酮-O-(5-苯基-1,3,4-噁二唑-2-甲基)肟醚化合物(4a~4f),用1H NMR、IR、MS和元素分析表征了其结构。 用MTT法测试了6种目标化合物对人黑色素瘤细胞株B16、人白血病细胞株HL60和人肝癌细胞株SMMC-7721的体外细胞毒活性。 测试结果表明,部分化合物对3种癌细胞具有潜在的体外生长抑制活性。     

牛筋果茎中一个新的异戊烯基异黄酮类化合物

综合运用硅胶柱色谱、ODS柱色谱、SephadexLH-20凝胶柱色谱以及制备型高效液相色谱(HPLC)等色谱分离手段,对苦木科牛筋果属植物牛筋果Harrisoniaperforata茎中的化学成分进行了研究,从其茎的95%乙醇提取物中分离得到了8个异戊烯基异黄酮类化合物,采用多种波谱鉴定方法确定了这些分离得到化合物的化学结构,其中化合物1为1个新的异戊烯基异黄酮类化合物,化合物2～8为从牛筋果属植物中分离得到的化合物.化合物1～8体外抑制肿瘤细胞生长的活性评价结果表明,它们对五种肿瘤细胞株(HL-60、A549、SMMC-7721、MCF-7和SW480)均具有较为显著的体外生长抑制活性,抑制肿瘤细胞生长的活性的IC₅₀范围为(0.38±0.03)～(31.68±0.21)μmol/L,抑制肿瘤细胞生长的活性与抗肿瘤阳性对照药顺铂的抑制活性相当.     

Flavonoid glycosides from Chromolaena odorata leaves and their in vitro cytotoxic activity

Two new flavonoid glycosides, (1, 2), and eleven known compounds, (3-13), were isolated from from a 70% EtOH extract of the leaves of Chromolaena odorata (Asteraceae). Their structures were elucidated by 1D and 2D NMR spectroscopic interpretation as well as by chemical studies. The newly isolated compounds were tested in vitro for their cytotoxic activities against the LLC and HL-60 cancer cell lines. Compound 1 showed cytotoxicity against LLC and HL-60 cancer cell lines with IC(50) values of 28.2 and 11.6 μM, respectively. Compound 2 exhibited significant cytotoxic activity in the inhibition of HL-60 cancer cell lines with IC(50) value of 10.8 μM.     

A new isoflavanone from the trunk of Horsfieldia pandurifolia

A new isoflavanone, 2,2′-epoxy-4′-methoxy-3,7-dihydroxyisoflavanone (1), and a new natural coumaranone, 2-hyroxy-2-(4′-methoxybenzyl)-6-methoxy-3-coumaranone (2), along with 26 known compounds, were first isolated from the trunk of Horsfieldia pandurifolia. Their structures were elucidated by the means of spectroscopic analysis. Compound 1 was assessed for its cytotoxicity against five human tumour lines (HL-60, SMMC-7721, A-549, MCF-7 and SW-480), and the result showed that it has no activity.     

长链醇和胺修饰的芳香氮芥衍生物的合成及生理活性

为了研究不同取代基对苯甲酸氮芥抗肿瘤活性的影响,以对氨基苯甲酸为起始原料,设计合成了6个新化合物,目标产物结构经元素分析、1H NMR和MS等确证.采用MTT法对白血病细胞HL-60、白血病细胞K562和肝癌细胞SMMC-7721进行了体外的抗肿瘤活性筛选.活性测试结果表明这些长链醇和胺修饰苯甲酸氮芥后,目标产物的抗肿瘤活性未得到提高,均弱于参照药物美法伦.     

Triterpenoids and diterpenoids from Viburnum chingii

Two new oleanane triterpenoids (1-2) and one new vibsane-type diterpenoid (3), together with 7 known compounds (4-10), were isolated from the leaves of Viburnum chingii. The structures of compounds 1-3 were elucidated by means of spectroscopic methods including extensive 1D- and 2D-NMR technique. Cytotoxicity of compounds 1-10 were tested against HL-60, SMMC-7721, A-549, SK-BR-3, and PANC-1 cell lines. Compound 3 showed significant cytotoxicity against HL-60, SK-BR-3, and PANC-1 cell lines.     

麦斛细胞毒活性成分研究

利用硅胶、聚酰胺柱层析等分离方法, 从麦斛全草的乙醚萃取物中分离得到4个化合物, 经化学方法和光谱分析(UV, IR, NMR, MS)鉴定为3,4,7-三羟基-2-甲氧基菲(1), 2,5-二羟基-4-甲氧基菲(2), eugenitin (3)和2,5-二羟基-4-甲氧基-9,10-二氢菲(4), 其中1为新化合物. 采用MTT法分别测得化合物1和2对体外培养的人急性髓性白血病细胞和人肝癌细胞增殖的抑制活性, 并分别考察了增敏剂葛根素对化合物1和2增殖活性的协同作用.     

Chemical constituents of Lycoris albiflora and their cytotoxic activities

An alcoholic extract of Lycoris albiflora (Amaryllidaceae) showed potent cytotoxic activity against HL-60 cells with an IC50 value of 1.7 microg/mL. Phytochemical examination of the extract resulted in the isolation of 15 alkaloids, including two phenanthridine-type alkaloids (1, 2), one benzylphenethylamine-type alkaloid (3), two crinane-type alkaloids (4, 5), one pyrrolophenanthridine-type alkaloid (6), six lycorenan-type alkaloids (7-12), and three galanthamine-type alkaloids (13-15), together with three neolignans (16-18), two flavans (19, 20), and two acetophenone derivatives (21, 22). Compound 3 (hostasinine A) has not been isolated from Amaryllidaceae plants, and 1, 2, 4, 5, 7-9, 11, 12 and 14-22 are the first isolation and identification from L. albiflora. The phenanthridine-type alkaloids (1, 2), as well as the alkaloids (3-5), exhibited potent cytotoxic activities against not only HL-60 cells but also HSC-2 cells, thus leading to the conclusion that these alkaloids are mainly responsible for the cytotoxicity of the L. albiflora extract. Compound 1 (lycoricidinol), with the most potent cytotoxic activities, induced apoptosis in both HL-60 cells and HSC-2 cells. It is notable that 1 induced transient autophagy and morphological changes in mitochondria in the early stages of the apoptotic cell death process in HSC-2 cells.     

两类氮芥衍生物的合成及其生理活性研究

设计合成了3个苯胺氮芥和6个萘酰亚胺-氮芥衍生物,产物结构均经1H NMR,13C NMR,ESI-MS和元素分析确认.使用MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]法测试了9个化合物对HL-60,K562和SMMC-7721三种...     

A new 12,17-cyclo-labdane diterpenoid from the twigs of Dacrycarpus imbricatus

A new 12,17-cyclo-labdane diterpenoid, podoimbricatin C (1), along with 15 known compounds was isolated from the twigs of Dacrycarpus imbricatus. Their structures were elucidated by means of extensive spectroscopic analysis. Compound 1 is the second example of the unusual 12,17-cyclo-labdane diterpenoids. It showed no inhibitory effects against five human tumour lines (HL-60, SMMC-7721, A-549, MCF-7 and SW-480).     

Cytotoxic ent-kaurane diterpenoids from Isodon henryi

Five new ent-kaurane diterpenoids, isodonhenrins A-E (1-5), together with thirteen known ones were isolated from the aerial parts of Isodon henryi. Their structures were identified by means of extensive spectroscopic analysis, and the absolute configurations of 1 were determined by single-crystal X-ray diffraction. Most of the diterpenoids were evaluated for their cytotoxicity against HL-60, SMMC-7721, A-549, MCF-7, and SW480 cell lines. Compound 17 showed significant inhibitory effects on five cell lines, and compounds 6, 9, 10, 11, 12 and 16 exhibited selective activity.