海洋放线菌Streptomyces sp.（No.30701）次生代谢产物研究

目的 研究一株海洋放线菌Streptomyces sp.（No.30701）的化学成分。方法 采用硅胶开放柱色谱、Sephadex LH-20凝胶柱色谱以及高效液相色谱等分离手段进行化合物的分离、纯化;利用理化性质和波谱学分析对单体化合物进行结构鉴定。结果 从海洋放线菌Streptomyces sp.（No.30701）发酵物中分离得到9个环二肽类化合物,分别鉴定为环(L-脯-L-缬)二肽（1）、环(D-脯-L-缬)二肽（2）、环(L-脯-L-亮)二肽（3）、环(4-羟基-脯-亮)二肽（4）、环(L-脯-L-异亮)二肽（5）、环(L-脯-L-酪)二肽（6）、环(L-亮-L-缬)二肽（7）、环(D-苯丙-甘)二肽（8）、环(L-苯丙-L-缬)二肽（9）。结论 以上化合物均为海洋放线菌常见的次生代谢产物,但化合物2、8含有天然界中不多见的D型氨基酸,并且化合物2是从链霉菌属放线菌中首次分离得到。     

海洋源放线菌Streptomyces sp. 223中二酮哌嗪类成分的研究

目的对采集自烟台逛荡河入海口沉积物的1株放线菌Streptomyces sp.223进行次级代谢产物及活性研究。方法采用硅胶柱层析、Sephadex LH-20凝胶层析、薄层层析以及HPLC等方法对放线菌Streptomyces sp.223发酵产物进行分离纯化,通过波谱数据分析及文献比较对化合物进行结构鉴定,并用MTT法初步评价其细胞毒活性。结果从该菌的发酵产物中分离到了7个二酮哌嗪类化合物,分别鉴定为（3S）-（1,4）-二甲基-3-异丙基-（2,5）二酮哌嗪（1）,环-（L-脯-L-苯丙）二肽（2）,环（L-脯-L-酪）二肽（3）,环（L-4-OH-脯-L-亮）二肽（4）,环（L-苯丙-甘）二肽（5）,环（L-4-OH-脯-L-苯丙）二肽（6）和环-（L-脯-L-缬）二肽（7）。结论化合物1作为1种天然产物为首次从海洋微生物中分离得到,且具有显著的细胞毒活性,对Hela细胞的半抑制浓度IC₅₀=18.7μmol·L^-1。     

海洋来源放线菌Demequina litorisediminis SCSIO 53428的化学成分研究

目的对南海深海沉积物来源的放线菌Demequina litorisediminis SCSIO 53428的发酵物化学成分进行研究。方法利用各种色谱技术,包括硅胶柱色谱、ODS反相柱色谱、Sephadex LH-20凝胶色谱、高效液相色谱等分离手段对放线菌Demequina litorisediminis发酵物的乙酸乙酯提取物进行分离纯化,通过波谱学数据分析并结合文献比较鉴定了化合物的结构。结果分离得到13个化合物,其结构分别为:环(L-酪-L-脯)二肽(1)、环(L-苯丙-L-脯)二肽(2)、环(L-缬-L-脯)二肽(3)、环(L-亮-L-脯)二肽(4)、环(反式-4-羟基-L-脯-L-亮)二肽(5)、环(甘-L-脯)二肽(6)、环(L-丙-L-脯)二肽(7)、环(缬-酪)二肽(8)、环(异亮-脯)二肽(9)、对羟基苯甲醛(10)、苯甲酸(11)、N-(2-羟基苯基)-乙酰胺(12)、2-乙酰氨基苯甲酸(13)。结论对海洋来源放线菌Demequina litorisediminis SCSIO53428的化学成分做了初步研究,化合物1～13均为首次从该属放线菌中分离得到。     

红树林真菌草酸青霉(092007)的环二肽类成分

目的研究海南文昌红树林真菌草酸青霉(Penicillium oxalicum)的代谢产物,寻找新的抗肿瘤活性化合物。方法利用硅胶、Sephadex LH-20、ODS柱色谱及制备型高效液相色谱等方法进行分离,通过化合物的理化性质及各种波谱技术鉴定它们的结构,采用MTT法评价化合物体外细胞毒活性。结果从真菌菌丝体的丙酮提取物中分离得到6个环二肽类化合物,鉴定其结构分别为:环(苯丙-异亮)二肽[cyclo-(Phe-Ile)](1)、环(苯丙-缬)二肽[cyclo-(Phe-Val)](2)、环(异亮-亮)二肽[cyclo-(Ile-Leu)](3)、环(缬-缬)二肽[cyclo-(Val-Val)](4)、环(脯-缬)二肽[cyclo-(Pro-Val)](5)、环(脯-甘)二肽[cyclo-(Pro-Gly)](6)。体外活性表明:化合物1、3和5在50μg.mL-1下对肝癌细胞HepG-Ⅱ的抑制率分别为31%、32%、17%,对前列腺癌细胞LNCaP抑制率分别为50%、43%、53%。结论这些化合物均为首次从该属真菌的代谢产物中分离得到,其中化合物2、3和5具有一定的细胞毒活性。     

海洋放线菌Micromonospora sp.(No.69)抗MRSA活性成分研究

目的对一株小单孢菌属放线菌Micromonospora sp.(No.69)的抗耐甲氧西林金黄色葡萄球菌(MRSA)活性成分进行研究。方法采用活性追踪分离的方法,通过硅胶开放柱色谱、Sephadex LH 20柱色谱、ODS开放柱色谱、反相高效液相色谱等手段对Micromonospora sp.(No.69)发酵液的甲醇提取物进行分离和纯化,利用ESI-MS、~1H-NMR、~(13)C-NMR等波谱技术对单体化合物进行结构鉴定。结果从Micromonosporasp.(No.69)发酵液的甲醇提取物中分离得到8个化合物,分别鉴定为:环(L-缬-L-脯)二肽(1)、环(L-异亮-L-脯)二肽(2)、环(L-亮-L-脯)二肽(3)、环(甘-L-脯)二肽(4)、环(苏-L-脯)二肽(5)、环(L-丙-L-脯)二肽(6)、环(L-酪-L-脯)二肽(7)、环(L-苯丙-L-脯)二肽(8)。抗MRSA活性测试结果表明化合物1和2对MRSA具有抑制作用,IC_(50)分别为3.2 mmol·L~(-1)和6.5 mmol·L~(-1)。结论以上化合物均为首次从该属菌株中分离得到,其中化合物1和2显示出抗MRSA活性。     

蝙蝠蛾拟青霉菌丝体中环二肽类化合物的分离与鉴定

目的研究蝙蝠蛾拟青霉菌丝体中环二肽类化合物的化学成分。方法采用硅胶柱色谱、制备型HPLC等色谱方法,对蝙蝠蛾拟青霉菌丝体的甲醇浸提物的正丁醇萃取物进行分离纯化,并根据理化性质及波谱数据鉴定分离得到化合物的结构。结果分离得到8个环二肽类化合物,经鉴定分别为环(脯-缬)二肽[cyclo(Pro-Val)](1)、环(脯-苯丙)二肽[cyclo(Pro-Phe)](2)、环(脯-异亮)二肽[cyclo(Pro-Ile)](3)、环(脯-亮)二肽[cyclo(Pro-Leu)](4)、环(亮-缬)二肽[cyclo(Leu-Val)](5)、环(苯丙-缬)二肽[cyclo(Val-Phe)](6)、环(丙-缬)二肽[cyclo(Val-Ala)](7)、环(丙-苯丙)二肽[cyclo(Ala-Phe)](8)。结论化合物1-8为首次从瓶梗青霉属植物中分离得到。     

海洋放线菌Micromonospora sp.(M2DG17)细胞毒活性成分研究

目的对海洋放线菌Micromonospora sp.(M2DG17)中的活性次生代谢产物进行研究。方法在活性追踪分离思路的指导下,综合利用硅胶开放柱色谱、ODS中低压柱色谱、Sephadex LH-20凝胶柱色谱以及高效液相色谱等分离技术进行化合物的分离、纯化;利用化合物理化性质和波谱学分析对单体化合物进行结构鉴定,并对其进行活性评价。结果从海洋放线菌Micromonospora sp.(M2DG17)发酵物中分离得到了7个化合物,分别鉴定为3-羟甲基-β-卡巴林(3-hydroxymethyl-β-carboline,1)、3-甲基-β-卡巴林(3-methyl-β-carbo-line,2)、β-卡巴林(β-carboline,3)、环(L-脯-L-苯丙)二肽[Cyclo-(L-Pro-L-Phe),4]、环(L-脯-L-缬)二肽[Cyclo-(L-Pro-L-Val),5]、环(L-脯-L-亮)二肽[Cyclo-(L-Pro-L-Leu),6]以及环(L-脯-L-异亮)二肽[Cyclo-(L-Pro-L-Ile),7],并对单体化合物进行了HCT116细胞生长抑制活性测试。结论化合物1~4、6为首次从该菌中分离得到,化合物2显示出弱的HCT116细胞生长抑制活性(IC50为65.0μmol.L-1)。     

海洋放线菌11014中抗肿瘤活性成分的研究Ⅰ.环二肽

为研究具有抗肿瘤活性的海洋放线菌11014发酵物中的活性成分，采用活性追踪的方法．经溶剂萃取、硅胶柱层析及制备HPLC等分离得到13个环二肽，通过理化性质及波谱学分析，分别确定为环（亮氨酸-丙氨酸）．环（亮氨酸-甘氨酸），环（异亮氨酸-丙氮酸），环（缬氮酸-丙氮酸）．环（丙氨酸-苯丙氮酸），环（苯丙氮酸-甘氮酸）．环（酪氮酸-甘氮酸），环（脯氮酸-酪氮酸），环（脯氨酸-苯丙氨酸），环（4-羟基-脯氮酸-苯丙氮酸）．环（4-羟基-脯氮酸-亮氨酸）．环（脯氮酸-缬氨酸），环（脯氮酸-亮氨酸）。首次以磺酰罗丹明法对这些化合物的抗肿瘤活性进行了测试，化合物环（4-羟基-脯氨酸-苯丙氨酸）具有较明显的抗肿瘤活性（5μg／ml浓度抑制率为48．3％）。     

五味子的环二肽及其合成

目的：研究五味子中的环肽成分。方法：用薄层色谱,硅胶及反向RP-18硅胶柱层析色谱和谱学方法。结果：分离到3个天然的环二肽及由3个环二肽组成的一个混合物并鉴定为环(亮-脯)(1),环(苯丙-脯)(2)和环(苯丙-亮)(3),环(苯丙-缬)(4),环(苯丙-异亮)(5),环(苯丙-苯丙)(6),另外,合成了14个环二肽类似物。结论：首次从五味子科植物北五味子中分离到环肽。环二肽2,6～8,14～20,经活性筛选表明,2,16及18有轻微的钙拮抗效应,19及20显示出增强高钾所致收缩效应。其它环二肽及它们的活性筛选工作正在进行中。     

海洋细菌NJ6-3-1次级代谢产物化学成分的分离与鉴定

目的研究海洋细菌NJ6-3-1次级代谢产物,以期得到有活性的先导化合物。方法采用硅胶柱色谱、凝胶柱色谱、HPLC等方法进行分离纯化,通过理化性质和波谱手段分析确定化合物的结构。结果从海洋细菌NJ6-3-1的乙酸乙酯萃取物中分离得到15个化合物,分别为环(色-脯)二肽(cyclo(Trp-Pro),1)、环(甘-脯)二肽(cyclo(Gly-Pro),2)、环(甘-苯丙)二肽(cyclo(Gly-Phe),3)、环(丙-苯丙)二肽(cylo(Ala-Phe),4)、环(酪-苯丙)二肽(cyclo(Tyr-Phe),5)、环(酪-脯)二肽(cy-clo(Tyr-Pro),6)、环(4-羟基-脯氨酸-苯丙氨酸)(cyclo(4-hydroxyl-Pro-Phe),7)、环(4-羟基-脯氨酸-亮氨酸)(cyclo(4-hydroxyl-Pro-Leu),8)、环(酪-亮)二肽(cyclo(Tyr-Leu),9)、环(丙-亮)二肽(cyclo(Ala-Leu),10)、环(甘-亮)二肽(cyclo(Gly-Leu),11)、环(丙-缬)二肽(cyclo(Ala-Val),12)、异光黄素(isolumichrome,13)、胸腺嘧啶(thymine,14)、尿嘧啶(uracil,15)。结论化合物1~15均为首次从海洋细菌NJ6-3-1次级代谢物中分离得到。     

Effect of abietane diterpenes from Plectranthus grandidentatus on the growth of human cancer cell lines

Five known abietane diterpenes, fatty acid esters of 7alpha-acyloxy-6beta-hydroxyroyleanone (1), grandidone A (2), 7alpha-acetoxy-6beta-hydroxyroyleanone (3), 6beta,7alpha-dihydroxyroyleanone (4), and coleon U (5), isolated from Plectranthus grandidentatus Gürke, were evaluated for their in vitro antiproliferative activity against five human cancer cell lines MCF-7, NCI-H460, SF-268, TK-10, and UACC-62. Coleon U (5) exhibited the strongest effect among all the assayed compounds. The abietane 3 revealed also a strong inhibitory effect while diterpenes 2 and 4 inhibited only slightly the growth of all cancer cell lines.     

Three new jatrophane-type diterpenes from Euphorbia pubescens

Three new macrocyclic jatrophane diterpene polyesters, named pubescenes A ( 1), B ( 2), and C ( 3), and the known compounds indole-3-aldehyde and scopoletin have been isolated and characterised from the whole dried plant of Euphorbia pubescens. The structures of the new compounds were established by spectroscopic means including 2D-NMR techniques such as COSY, HMQC, HMBC and NOESY experiments. Compounds 1 - 3 were evaluated for their in vitro effect on the growth of three human cancer cell lines MCF-7 (breast), NCI-H460 (lung) and SF-268 (CNS) as well as for their capacity to interfere with the proliferation of human peripheral blood lymphocytes. They exhibited a moderate growth inhibitory effect on the cancer cell line NCI-H460. No effect was observed on the mitogenic response of human lymphocytes to PHA.     

Euphopubescenol and euphopubescene, two new jatrophane polyesters, and lathyrane-type diterpenes from Euphorbia pubescens

The structures of euphopubescenol and euphopubescene, two new macrocyclic jatrophane diterpene polyesters, isolated from the whole dried plant of Euphorbia pubescens, were established as 5alpha,8alpha,15beta-triacetoxy-3alpha-benzoyloxy -4alpha-hydroxy -9,14-dioxo-13beta H-jatropha-6(17),11 E-diene ( 1) and 3beta,7beta,8beta,9alpha,14alpha,15beta-hexaacetoxy-2beta H-jatropha-5 E,11 E-diene ( 2) by 1D- and 2D-NMR (COSY, HMQC, HMBC and NOESY), IR, EI-MS and EI-FTICR-MS. Two known lathyrane derivatives, jolkinol A ( 3) and jolkinol A ( 4), whose (13)C-NMR spectra were assigned, were also isolated. Compounds 1 - 3 have been evaluated for their ability to inhibit the in vitro growth of three human tumour cell lines representing different tumour types, MCF-7 (breast adenocarcinoma), NCI-H460 (non-small cell lung cancer) and SF-268 (CNS cancer). They inhibited both MCF-7 and NCI-H460 cell lines, with GI50 values ranging between 40.9 microM and 95.3 microM, but were found to be ineffective as growth inhibitors of the SF-268 cell line.     

Antimycins A10 approximately A16, seven new antimycin antibiotics produced by Streptomyces spp. SPA-10191 and SPA-8893

Seven new antimycin antibiotics, named antimycins A10, A11, A12, A13, A14, A15 and A16, were isolated from the fermentation broth of strains of Streptomyces spp. SPA-10191 and SPA-8893, along with known antimycins A1, A2, A3 and A4. The structures of the new antimycins were determined by spectral analyses, including 2D NMR techniques. These compounds exhibited antifungal activity against Candida utilis.     

Antitumor and antileishmanial evaluation of novel heterocycles derived from quinazoline scaffold: a molecular modeling approach

Novel thiazole, pyrimidine and benzylidene derivatives derived from quinazoline scaffold have been synthesized. The antitumor evaluation of the newly synthesized products against three cancer cell lines namely breast adenocarcinoma (MCF-7), non-small cell lung cancer (NCI-H460), and CNS cancer (SF-268) showed that the benzylidene–quinazoline derivative 12a showed remarkable activity against all three cell lines. The thiazolo-quinazoline derivative 10 showed greater activity than the control against breast adenocarcinoma (MCF-7) with a concentration of 0.01 μM. Moreover, the antileishmanial activity of the newly synthesized products tested on Leishmania donovani amastigotes showed that compounds 4, 14, and 18 had very promising activity.     

Cytotoxic trichothecene macrolides from the endophyte fungus Myrothecium roridum

A new cytotoxic roridin-type trichothecene macrolide named epiroridin acid (1) and two known compounds epiroridin E (2) and mytoxin B (3) were isolated from the liquid culture of Myrothecium roridum A553, which was isolated from the medicinal plant Pogostemon cablin. The structure of the new macrolide (1) was elucidated by extensive spectroscopic measurements (UV, IR, MS, and 1D and 2D NMR) analyses. All isolated compounds (1–3) were evaluated for their cytotoxic activities against SF-268, MCF-7, NCI-H460, and HepG-2 tumor cell lines. The new compound (1) exhibited well cytotoxicity against the four selected tumor cell lines.     

海洋青霉属真菌菌株XGH2321抑菌活性代谢产物的分离与鉴定

目的从青霉属真菌XGH2321的发酵液中分离抑菌活性次级代谢产物。方法发酵液经乙酸乙酯萃取、正相硅胶柱层析、C18柱制备色谱分离获得单体,并对化合物进行结构鉴定及活性测试。结果从菌株XGH2321的乙酸乙酯提取物中分离得到3个己酮烯类化合物及1个酯类化合物,根据化合物的光谱特征(ESI-MS、1H-NMR和13C-NMR)和理化性质分别鉴定为sorbicillin(1),2’,3’-dihydrosorbicillin(2),2,3-Dihydro-7-hydroxy-6,8-dimethyl-2-[(E)-prop-l-enyl]chromen-4-one(3)和dibutylphthalate(4),其中化合物3和4对耐甲氧西林金黄色葡萄球菌(MRSA)的生长具有明显的抑菌活性,化合物1、2、3对白色念珠菌(Candida albicans)的生长具有明显的抑菌活性,化合物1和2对烟曲霉(Aspergillus fumigatus)对的生长具有明显的抑菌活性。结论化合物2和3的抗MRSA作用,化合物1和3的抗白色念珠菌作用及化合物1、2和3的抗烟曲霉作用属首次报道。     

Cytotoxicities of xanthones and cinnamate esters from Hypericum hookerianum

5-Hydroxy-2-methoxyxanthone (1), 2-hydroxy-3-methoxyxanthone (2), trans-kielcorin (3), 4-hydroxy-3-methoxyphenyl ferulate (4) and 3beta-O-caffeoylbetulinic acid (5) were isolated from Hypericum hookerianum. Compounds 1-5 were tested against the growth of three human tumor cell lines, MCF-7, NCI-H460 and SF-268. Compounds 4 and 5 exhibited significant inhibitory activity effects against all three; GI50 values for 4 were 15.1 +/- 1.6, 18.7 +/- 2.3 and 15.9 +/- 2.7 and for 5 12.2 +/- 2.4, 19.6 +/- 2.3 and 24.3 +/- 2.5. Compound 3 was less active with GI50 values of 55.1 +/- 2.3, 49.7 +/- 3.0 and 40.5 +/- 1.5, while 1 and 2 exhibited only weak effects. Compounds 4 and 5 were moderately effective in influencing the mitogenic response to human lymphocytes to hemoagglutinin, with IC values of 26.1 +/- 3.6 and 40.8 +/- 4.9, respectively.     

1-{2-[(4-取代苯基)甲氧基]-2-(取代苯基)乙基}-1H-氮唑类化合物的合成及抗真菌活性

根据氮唑类抗真菌化合物的构效关系和作用机理,设计合成了29个1-{2-[(4-取代苯基)甲氧基]-2-(取代苯基)乙基}-1H-氮唑类化合物,其中九个为首次报道。初步体外抑菌试验结果表明,大多数目标化合物对八种试验菌株都有不同程度的抗真菌活性。化合物14对白念珠菌的活性与克霉唑及益康唑相当,对其它七种试验菌株的活性明显强于克霉唑及益康唑。化合物4,12对白念珠菌活性差,对其它七种试验菌株的活性也强于克霉唑和益康唑。化合物5,6和23除对白念珠菌外,对其它七种试验菌株,也有较强活性。     

1-{2-[(4-取代苯基)甲氧基]-2-(取代苯基)乙基}-1H-氮唑类化合物的合成及抗真菌活性

根据氮唑类抗真菌化合物的构效关系和作用机理,设计合成了29个1-{2-[(4-取代苯基)甲氧基]-2-(取代苯基)乙基}-1H-氮唑类化合物,其中九个为首次报道。初步体外抑菌试验结果表明,大多数目标化合物对八种试验菌株都有不同程度的抗真菌活性。化合物14对白念珠菌的活性与克霉唑及益康唑相当,对其它七种试验菌株的活性明显强于克霉唑及益康唑。化合物4,12对白念珠菌活性差,对其它七种试验菌株的活性也强于克霉唑和益康唑。化合物5,6和23除对白念珠菌外,对其它七种试验菌株,也有较强活性。