Cytotoxic Mannopyranosides of Indole Alkaloids from Zanthoxylum nitidum

Three new mannopyranosides of indole alkaloids, methyl 7‐(β‐D ‐mannopyranosyloxy)‐1H‐indole‐2‐carboxylate ( 1 ), methyl 7‐[(3‐O‐acetyl‐β‐D ‐mannopyranosyl)oxy]‐1H‐indole‐2‐carboxylate ( 2 ), and 2‐methyl‐1H‐indol‐7‐yl β‐D ‐mannopyranoside ( 3 ), were isolated from an EtOH extract of the roots of Zanthoxylum nitidum. Their structures were identified as new compounds on the basis of the spectroscopic analyses. Bioactivity evaluation revealed that these alkaloids possess significant cytotoxicities against all the tested tumor cell lines with IC₅₀ values of less than 30 μM .     

Benzophenanthridine alkaloids from Zanthoxylum nitidum (Roxb.) DC, and their analgesic and anti-inflammatory activities

Seven benzophenanthridine alkaloids, 1-7, were isolated from the roots of Zanthoxylum nitidum. Among them, two novel alkaloids, named (R)-8-[(R)-1-hydroxyethyl]dihydrochelerythrine (1) and 8-methoxynorchelerythrine (2), were structurally identified as new compounds on the basis of the spectroscopic analysis. Bioactivity evaluation showed that nitidine (3), dihydrochelerythrine (4), oxyavicine (5), 8-methoxychelerythrine (6), and 8-hydroxydihydrochelerythrine (7) exhibit comparable analgesic and anti-inflammatory effects as hydrocortisone.     

超声波提取两面针中的总碱

在提取两面针总碱时,超声提取法与回流提取法相比较,具有省时、节能、提出率高的等优点。     

Alkaloids from the roots of Zanthoxylum nitidum and their antiviral and antifungal effects

Five alkaloids, 5,6-dihydro-6-methoxynitidine (1), dictamnine (2), gamma-fagarine (3), skimmianine (4), and 5-methoxydictamnine (5), were isolated from the roots of Zanthoxylum nitidum. Their structures and configurations were elucidated by spectroscopic methods and X-ray analysis. Compounds 1, 4, and 5 showed in vitro antiviral effect against hepatitis B virus, and compounds 2, 3, and 5 demonstrated marked antimitotic and antifungal activity.     

两面针化学成分、药理活性及抗肿瘤机制研究进展

本文主要结合近几年的国内外研究报道,综述了中国传统中草药-两面针的化学成分、药理活性及临床疗效等方面的研究进展;并结合作者所在课题组的研究成果,重点介绍了两面针生物碱及其金属配合物的抗肿瘤活性研究。     

两面针中新棒状花椒酰胺提取工艺的研究

本研究通过正交试验设计,对两面针中具有镇痛、抗炎和止血活性的新棒状花椒酰胺提取的不同溶剂、不同的提取时间和不同的提取温度用工业上常用的回流提取方法,进行了最佳工艺条件的选择。发现不同的提取条件,两面针的提取液中活性成分新棒状花椒酰胺的含量差别很大。在75％的乙醇、75℃温度、时间3h的条件下,两面针的提取液中新棒状花椒酰胺的含量最高,为0．76％;在水为溶剂、50℃温度、时间1h的条件下的条件下,两面针的提取液中新棒状花椒酰胺的含量最低,为0．00070％。     

正交设计和动态过程优化两面针超声提取工艺

以总生物碱提取率为指标,先用正交试验优化两面针的超声提取工艺,再动态过程精选提取工艺。最佳工艺条件为:复合酶预处理后,以体积分数60%乙醇(盐酸5 g/L)超声(250 W)提取3次,第1次以10倍量溶剂提取15 min,第2次以4倍量溶剂提取12 min,第3次以3倍量溶剂提取9 min,总生物碱提取率87.80%。该工艺高效、节能、省时,为工业生产奠定了实验基础。     

毛两面针挥发油化学成分

利用气相色谱-质谱联用技术对广西柳州地区大瑶山的毛两面针挥发油化学成分进行了研究,共鉴定出20种成分,占挥发油成分的45.72%。其中主要成分为倍半萜。     

Cytotoxic alkaloids from the bulbs of Fritillaria hupehensis

Phytochemical investigation of the bulbs of Fritillaria hupehensis resulted in the isolation and structural elucidation of four new steroidal penta- and hexacyclic veratraman- and cevan-based alkaloids, respectively, compounds 1-4. They were obtained together with the known constituents ebeinine (5) and zhebeinine (6), which were isolated for the first time from this plant. The structures of the new isolates were established by spectroscopic and mass-spectrometric analyses, in combination with chemical methods. All compounds were assayed for their cytotoxic effects towards HeLa and HepG2 cell lines. Compounds 1 and 2 showed significant inhibitory effects against both types of tumor cells, with IC(50) values in the range 2.52-0.23 microM, similar as those for 5-fluorouracil used as positive control.     

两面针提取物(S-O)对小鼠镇痛、抗炎和止血作用的研究

本研究对两面针根的提取物S-O进行了镇痛、止血和抗炎药理实验,每种作用选用两种实验方法来评价。镇痛作用采用热板法和扭体法。热板法实验显示,S-O在150mg/kg剂量时,小鼠痛阈值明显提高（P〈0．01）;扭体法实验显示,S-O在150mg/kg剂量为时,对冰醋酸致痛的小鼠扭体反应次数减少了70．96％（P〈0．01）。抗炎实验采用二甲苯致小鼠耳廓肿胀法及腹腔染料渗出法。二甲苯致炎剂实验表明,S-O在150mg/kg剂量时,对二甲苯所致小鼠耳廓肿胀有明显抑制作用,抑制率为63．45％（P〈0．01）;冰醋酸所致的腹腔毛细血管通透性实验中,S-O在150mg/kg和75mg/kg两个剂量组时,对小鼠的抗炎效果分别为52．94％（P〈0．01）和52．00％（P〈0．01）。止血实验采用毛细玻璃管法和载玻片法。毛细玻璃管实验表明S-O在150mg/kg和75mg/kg两个剂量时,凝血时间明显缩短（P〈0．01）;载玻片实验表明S-O在150mg/kg剂量时,凝血时间明显缩短（P〈0．01）。总之,两面针中提取物S-O对小鼠具有显著的镇痛、止血和抗炎作用。     

两面针提取物(S0)对小鼠镇痛、抗炎和止血作用的研究(英文)

本研究对两面针根的提取物S0进行了镇痛、止血和抗炎药理实验,每种作用选用两种实验方法来评价。镇痛作用采用热板法和扭体法。热板法实验显示,S0在150mg/kg剂量时,小鼠痛阈值明显提高(P<0.01);扭体法实验显示,S0在150mg/kg剂量为时,对冰醋酸致痛的小鼠扭体反应次数减少了70.96%(P<0.01)。抗炎实验采用二甲苯致小鼠耳廓肿胀法及腹腔染料渗出法。二甲苯致炎剂实验表明,S0在150mg/kg剂量时,对二甲苯所致小鼠耳廓肿胀有明显抑制作用,抑制率为63.45%(P<0.01);冰醋酸所致的腹腔毛细血管通透性实验中,S0在150mg/kg和75mg/kg两个剂量组时,对小鼠的抗炎效果分别为52.94%(P<0.01)和52.00%(P<0.01)。止血实验采用毛细玻璃管法和载玻片法。毛细玻璃管实验表明S0在150mg/kg和75mg/kg两个剂量时,凝血时间明显缩短(P<0.01);载玻片实验表明S0在150mg/kg剂量时,凝血时间明显缩短(P<0.01)。总之,两面针中提取物S0对小鼠具有显著的镇痛、止血和抗炎作用。     

Chemical Constituents of Crinum asiaticum L. var. sinicum Baker and Their Cytotoxic Activities

A phytochemical investigation of the bulbs of Crinum asiaticum L. var. sinicum Baker resulted in the isolation of two new alkaloids, asiaticumines A and B ( 1 and 2 , resp.), together with 21 known compounds, including nine alkaloids, four amides, five phenolic compounds, and three flavonoids. All 23 compounds were isolated for the first time from Crinum asiaticum L. var. sinicum Baker . Their structures were elucidated by spectroscopic methods. In addition, ten alkaloids, 1 – 10 , were evaluated for their cytotoxic activities against human tumor cell lines A549, LOVO, HL‐60, and 6T‐CEM. Compounds 3, 4 , and 7 – 10 selectively showed remarkable inhibition against one or more of the tested cell lines.     

毛两面针挥发油化学成分及其生物活性

研究了毛两面针挥发油抑菌作用。抗菌实验结果表明,水蒸馏法提取的挥发油对金黄色葡萄球菌、白色念珠菌有明显的抑菌作用,乙醚提取的挥发油原液对金黄色葡萄球菌、大肠杆菌、绿脓杆菌、白色念珠菌有明显的抑菌作用。采用GC/MS分析了水蒸汽所得挥发油的化学成分,鉴定了20种物质,其中,主要成分是倍半萜。(-)-spathulenol、-γelemene和germacrene D等已被报道有抑菌作用的成分含量分别为12.53%、1.75%和1.44%。     

Melanogenesis‐Inhibitory and Cytotoxic Activities of Diarylheptanoids from Acer nikoense Bark and Their Derivatives

Nine cyclic diarylheptanoids, 1 – 9 , including two new compounds, i.e., 9‐oxoacerogenin A ( 8 ) and 9‐O‐β‐D ‐glucopyranosylacerogenin K ( 9 ), along with three acyclic diarylheptanoids, 10 – 12 , and four phenolic compounds, 13 – 16 , were isolated from a MeOH extract of the bark of Acer nikoense (Aceraceae). Acid hydrolysis of 9 yielded acerogenin K ( 17 ) and D ‐glucose. Two of the cyclic diarylheptanoids, acerogenin A ( 1 ) and (R)‐acerogenin B ( 5 ), were converted to their ether and ester derivatives, 18 – 24 and 27 – 33 , respectively, and to the dehydrated derivatives, 25, 26, 34 , and 35 . Upon evaluation of compounds 1 – 16 and 18 – 35 for their inhibitory activities against melanogenesis in B16 melanoma cells, induced with α‐melanocyte‐stimulating hormone (α‐MSH), eight natural glycosides, i.e., six diarylheptanoid glycosides, 2 – 4, 6, 9 , and 12 , and two phenolic glycosides, 15 and 16 , exhibited inhibitory activities with 24–61% reduction of melanin content at 100 μM concentration with no or almost no toxicity to the cells (88–106% of cell viability at 100 μM ). In addition, when compounds 1 – 16 and 18 – 35 were evaluated for cytotoxic activity against human cancer cell lines, two natural acyclic diarylheptanoids, 10 and 11 , ten ether and ester derivatives, 18 – 22 and 27 – 31 , and two dehydrated derivatives, 34 and 35 , exhibited potent cytotoxicities against HL60 human leukemia cell line (IC₅₀ 8.1–19.3 μM ), and five compounds, 10, 11, 20, 29 , and 30 , against CRL1579 human melanoma cell line (IC₅₀ 10.1–18.4 μM ).     

两面针药材挥发油的GC-MS分析

采用气相色谱-质谱（GC-MS）联用方法对广西产两面针药材的挥发油成分进行分析,共分离出80余个组份,通过质谱数据库检索和图谱分析,并参考相应的保留时间确定了其中的58个组分,总相对含量占挥发油的91．4％。其中含量最大的是斯杷土烯醇（55．21％）,其次有异斯杷土烯醇（6．35％）、异香树素环氧化物（3．88％）、2-十三烷酮（3．28％）和α-香附酮（2．14％）等。     

Cytotoxic acridone and indoloquinazoline alkaloids from Zanthoxylum poggei

Two new alkaloids, poggeicridone (1) and 2-methoxy-7,8- dehydroruteacarpine (6), together with nine known compounds, were isolated from the dichloromethane (DCM) extract of the bark of Zanthoxylum poggei (Engl.) P. G. Waterman. The structures of all compounds were determined by comprehensive spectroscopic analyses (1D and 2D NMR and EI- and ESI⿿MS). Compounds 5-9 exhibited strong suppressive effects on the phagocytosis response upon activation with serum opsonized zymosan in the in vitro oxidative burst studies using whole blood. The IC₅₀ values were in the range of 12.0⿿25.9 μM. These compounds displayed a moderate level of cytotoxic activity against the human Caucasian prostate adenocarcinoma cell line PC-3, with IC₅₀ values of 15.8 and 22.1 μM (the IC₅₀ value of the positive control standard doxorubicin was IC₅₀ 0.9 μM). All isolated compounds were also tested against plant pathogenic bacteria, fungi and oomycetes using the paper disk agar diffusion assay, resulting in no significant activities (MICs > 1 mg/mL).     

Secondary metabolites from the root wood of Zanthoxylum wutaiense and their antitubercular activity

Bioassay‐guided fractionation of the root wood of Zanthoxylum wutaiense led to the isolation of five new compounds, wutaipyranol A ( 1 ), 8‐methoxywutaipyranol A ( 2 ), demethoxywutaiensal ( 3 ), demethoxywutaiensol ( 4 ), and dihydrodemethoxywutaiensol ( 5 ), together with six known compounds. Their structures were elucidated by 1D‐ and 2D‐NMR, as well as MS analyses. Among the isolates, wutaipyranol A ( 1 ), 8‐methoxywutaipyranol A ( 2 ), and demethoxywutaiensal ( 3 ) exhibited antitubercular activities against Mycobacterium tuberculosis H₃₇Rv in vitro, with MIC values of 52.4, 55.6, and 45.8 μg/ml, respectively.     

In vitro Leishmanicidal and Cytotoxic Activities of the Glycoalkaloids from Solanum lycocarpum (Solanaceae) Fruits

Leishmaniasis is an infection caused by a protozoan parasite of the genus Leishmania and is the second most prevalent parasitic protozoal disease after malaria in the world. We report the in vitro leishmanicidal activity on promastigote forms of Leishmania amazonensis and cytotoxicity, using LLCMK₂ cells, of the glycoalkaloids from the fruits of Solanum lycocarpum, determined by colorimetric methods. The alkaloidic extract was obtained by acid‐base extraction; solamargine and solasonine were isolated by silica‐gel chromatography, followed by reversed‐phase HPLC final purification. The alkaloidic extract, solamargine, solasonine, as well as the equimolar mixture of the glycoalkaloids solamargine and solasonine displayed leishmanicidal activity against promastigote forms of L. amazonensis, whereas the aglycone solasodine was inactive. After 24 and 72 h of incubation, most of the samples showed lower cytotoxicities (IC₅₀ 6.5 to 124 μM ) as compared to leishmanicidal activity (IC₅₀ 1.1 to 23.6 μM ). The equimolar mixture solamargine/solasonine was the most active with an IC₅₀ value of 1.1 μM , after 72 h. Likewise, solamargine was the most active after 24 h with an IC₅₀ value of 14.4 μM , both in comparison with the positive control amphotericin B.     

Melanogenesis‐Inhibitory and Cytotoxic Activities of Limonoids,Alkaloids, and Phenolic Compounds from Phellodendron amurense Bark

Four limonoids, 1  –  4 , five alkaloids, 5  –  9 , and four phenolic compounds, 10  –  13 , were isolated from a MeOH extract of the bark of Phellodendron amurense (Rutaceae). Among these, compound 13 was new, and its structure was established as rel‐(1R,2R,3R)‐5‐hydroxy‐3‐(4‐hydroxy‐3‐methoxyphenyl)‐6‐methoxy‐1‐(methoxycarbonylmethyl)indane‐2‐carboxylic acid methyl ester (γ‐di(methyl ferulate)) based on the spectrometric analysis. Upon evaluation of compounds 1  –  13 against the melanogenesis in the B16 melanoma cells induced with α‐melanocyte‐stimulating hormone (α‐MSH), four compounds, limonin ( 1 ), noroxyhydrastinine ( 6 ), haplopine ( 7 ), and 4‐methoxy‐1‐methylquinolin‐2(1H)‐one ( 8 ), exhibited potent melanogenesis‐inhibitory activities with almost no toxicity to the cells. Western blot analysis revealed that compound 6 inhibited melanogenesis, at least in part, by inhibiting the expression of protein levels of tyrosinase, TRP‐1, and TRP‐2 in α‐MSH‐stimulated B16 melanoma cells. In addition, when compounds 1  –  13 were evaluated for their cytotoxic activities against leukemia (HL60), lung (A549), duodenum (AZ521), and breast (SK‐BR‐3) cancer cell lines, five compounds, berberine ( 5 ), 8 , canthin‐6‐one ( 9 ), α‐di‐(methyl ferulate) ( 12 ), and 13 , exhibited cytotoxicities against one or more cancer cell lines with IC₅₀ values in the range of 2.6 – 90.0 μm . In particular, compound 5 exhibited strong cytotoxicity against AZ521 (IC₅₀ 2.6 μm ) which was superior to that of the reference cisplatin (IC₅₀ 9.5 μm ).     

Biological Evaluation of Secondary Metabolites from the Root of Machilus obovatifolia

Bioassay‐guided fractionation of the root of Machilus obovatifolia led to the isolation of four new lignans, epihenricine B ( 1 ), threo‐(7′R,8′R) and threo‐(7′S,8′S)‐methylmachilusol D ( 2 and 3 ), and isofragransol A ( 4 ), along with 23 known compounds. The compounds were obtained as isomeric mixtures (i.e., 2 / 3 and 4 / 20 , resp.). The structures were elucidated by spectral analyses. Among the isolates, 1 , licarin A ( 12 ), guaiacin ( 14 ), (±)‐syringaresinol ( 21 ), and (?)‐epicatechin ( 23 ) showed ABTS (=2,2′‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonic acid) cation radical‐scavenging activity, with SC₅₀ values of 11.7±0.5, 12.3±1.1, 11.0±0.1, 10.6±0.3, and 9.5±0.2 μM in 20 min, respectively. In addition, kachirachirol B ( 17 ) showed cytotoxicity against the NCI‐H460 cell line with an IC₅₀ value of 3.1 μg/ml.