微紫青霉中的化学成分研究

目的：研究微紫青霉代谢产物对稻瘟霉分生孢子和菌丝体的生长抑制作用。方法：通过理化性质和光谱数据的分析鉴定结构，利用稻瘟霉模型测试活性。结果与结论：从微紫青霉代谢产物中分离得到了4个化合物，分别鉴定为3-(1-甲基乙基)-6-(1-甲基丙基)-2，5-哌嗪二酮（Ⅰ）、（3S，8аS）-3-甲基-1，2，3，4，6，7，8，8а-八氢吡咯骈[1，2а]-吡嗪-1，4-二酮（Ⅱ）、二十二烷酸（Ⅲ）、2-甲酰基-3，5-二羟基-4-甲基苯甲酸（Ⅳ）。上述4个化合物均对稻瘟霉分生孢子和菌丝体的生长有一定的抑制作用。     

云南土壤真菌07—11号菌株中的活性成分

从云南土壤真菌07－11发酵液乙酸乙酯层浸膏中得到5个活性成分,经光谱数据分析和理化鉴别,分别鉴定为邻羟基苯甲酸（Ⅰ）、4,6－二羟基－5－甲基－1（3H）异苯骈呋喃酮（Ⅱ）、2－甲酰基－3,5－二羟基－4－甲基苯甲酸（Ⅲ）、N－（4－羟基－2－甲氧苯基）乙酰胺（Ⅳ）以及麦角甾－7,22－二烯－3,6－二酮（Ⅴ）,它们对稻瘟霉分生孢子及菌丝体都有一定抑制作用。其中化合物Ⅳ为首次分离得到的天然产物,其谱学数据也是首次报道。     

海洋细菌Bacillus sp.发酵液中的化学成分

目的 研究海洋细菌Bncillus sp．发酵液中的化学成分，研究其成分对稻瘟霉的抑制作用，为从海洋微生物代谢产物中寻找新型抗肿瘤、抗真菌活性物质奠定基础。方法 利用各种色谱技术进行分离，根据光谱数据鉴定结构。结果 从中分离得到4个成分，分别鉴定为吡咯并[1，2α]哌嗪-3，6-二酮(I)、尿素(Ⅱ)、苯乙酸(Ⅲ)、3-甲基-2，5-哌嗪二酮(Ⅳ)。结论 化合物I、Ⅲ、Ⅳ对稻瘟霉分生孢子或菌丝体有一定的抑制作用；化合物I、Ⅳ为首次从本属菌种发酵液中分离得到。     

海洋细菌Bacillus sp.发酵液中化学成分的研究

目的：研究海洋细菌Bacillus sp．菌株发酵液的化学成分．研究其成分对稻瘟霉的抑制情况．为从海洋微生物代谢产物中寻找新型抗肿瘤、抗真菌活性物质奠定基础。方法：利用各种色谱层析技术进行分离．根据光谱数据鉴定其结构。结果：从中分离得到8个成分．分别鉴定为吡咯并哌嗪2，5-二酮(Ⅰ)、3-异丁基-吡咯并哌嗪2，5-二酮(Ⅱ)、3-甲基-哌嗪-2，5-二酮(Ⅲ)、胸腺嘧啶(Ⅳ)、尿嘧啶(Ⅴ)、曲酸(Ⅵ)、丁四醇(Ⅶ)、苯丙氨酸(Ⅷ)。结论：其中化合物Ⅰ，Ⅱ，Ⅲ对稻瘟霉分生孢子或菌丝体有一定抑制作用；化合物Ⅵ为首次从本属菌中分离得到。     

产紫青霉中的活性成分

从陕西省采集的土样中分离得到产紫青霉 (Penicillium purpurogenumStoll) ,从其发酵液乙酸乙酯萃取物中分离得到两个化合物 ,经过光谱数据的分析鉴定为 :3 (1′ 羧基乙烯氧基 )苯甲酸和间羟基苯甲酸 ,并利用稻瘟霉 (Pyriculariaoryzae)菌丝体形态变化作为活性指标 ,测定了它们的活性     

红葱抗稻瘟霉活性成分研究

目的阐明红葱抗稻瘟霉活性的物质基础.方法利用稻瘟霉筛选体系对红葱的60%(φ)乙醇提取物及其氯仿、正丁醇和水的萃取部分进行活性筛选,并对活性部位的化学成分进行分离鉴定.结果与结论从活性部位中分离得到10个化合物,通过理化性质和波谱数据鉴定它们的结构分别为:异红葱甲素(1)、异红葱乙素(2)、红葱乙素(3)、β-谷甾醇(4)、8-羟基-3,4-二甲氧基-1-甲基-蒽醌-2-羧酸甲酯(5)、4-羟基红葱乙素(6)、hongconin(7)、4,8-二羟基-3-甲氧基-1-甲基-蒽醌-2-羧酸甲酯(8)、dihydro-eleutherinol(9)、1,3,6-三羟基-8-甲基蒽醌(10).其中,9和10为首次从该属植物中分得.化合物2、3、5、6、7、9、10具有较好的诱导稻瘟霉菌丝变形的活性,它们的最小变形浓度(minimummorphologicaldeformationconcentrate,MMDC)分别为30、30、170、130、55、60、150μmol·L-1.用MTT法测定10个化合物的抗肿瘤活性,发现化合物2、3、5、6、7、9有较强的抑制人类红白血病细胞株K562细胞生长的活性,它们的IC50值分别为33、49、266、35、174、154μmol·L-1.     

抗稻瘟霉活性化合物A73的结构鉴定

以稻瘟霉分生孢子生长形态异常或抑制为指标，从土壤真菌中筛选新抗真菌、抗肿瘤活性物质的过程中，得到活性菌株１３１〔１〕．通过对其次级代谢产物进行活性跟踪分离，得到活性化合物３，４二氢９，１０二羟基７甲氧基３甲基１Ｈ萘并〔２，３ｃ〕吡...     

太平洋侧花海葵中的化学成分(Ⅱ)

目的:研究太平洋侧花海葵的活性成分。方法:采用稻瘟霉模型生物活性追踪方法,应用多种色谱技术进行分离,理化性质和波谱数据鉴定其结构。结果:分离并鉴定了 5个化合物,5α,8α-过氧麦角甾-6,22-二烯-3β-醇(Ⅰ),对羟基苯甲醛(Ⅱ),N-甲基吡啶-2-羧酸盐(Ⅲ),脲基甲酸乙酯(Ⅳ),牛磺酸(Ⅴ),其中化合物和对稻瘟霉的最小菌丝变形浓度分别为0.46mmol·L~(-1)和1.9mmol·L~(-1)。结论:5个化合物均为首次从该种海葵中获得,化合物和具有诱导稻瘟霉菌丝变形活性。     

葫芦茶化学成分的研究

目的研究葫芦茶的化学成分。方法采用柱色谱技术对葫芦茶提取物进行分离纯化,采用波谱技术结合化学方法进行结构鉴定。结果与结论从葫芦茶中分离得到了8个化合物,分别鉴定为3,4-二氢-4-(4'-羟基苯基)-5,7-二羟基香豆素(1)、二氢槲皮素(2)、顺式对羟基肉桂酸(3)、反式对羟基肉桂酸(4)、原儿茶酸乙酯(5)、4-羟基-3,5-二甲氧基苯甲酸(6)、4-羟基-3-甲氧基苯甲酸(7)、对羟基苯甲酸(8)。结论化合物1~4均为首次从该植物中分离得到。     

山楂叶中芳香族化合物的分离和鉴定

目的研究阐明山楂(Crataegus pinnatifida Bge.)叶的化学成分。方法运用硅胶柱色谱、Sephadex LH-20柱色谱、ODS柱色谱、制备HPLC等分离手段进行化学成分的分离纯化,根据理化性质和波谱数据鉴定其结构。结果从山楂叶体积分数为80%乙醇提取物中分离得到13个芳香族化合物,分别鉴定为3-乙氧基-4-羟基苯甲酸(1)、3,4-二甲氧基苯丙醛(2)、对乙氧基苯甲酸(3)、对甲基苯甲酸(4)、对羟基苯甲酸(5)、3-甲氧基-4-甲基苯甲酸(6)、对甲氧基苯丙酸(7)、对甲氧基苯丙醛(8)、反式对乙氧基桂皮酸(9)、1-(3,4,5-三甲氧基苯基)乙烷-1’S,2’-二醇(10)、3-甲氧基对羟基苯甲醛(11)、对羟基苯甲醛(12)、6-羟基苯甲酸苄酯-2-O-β-D-葡萄糖苷(13)。结论化合物1、2为新天然产物,3～13为首次从山楂属植物中分离得到。     

The synthesis of potential anticancer drugs related to mitoxantrone

ABSTRACT In an attempt at a rational design for anticancer drugs, two new potential anticancer compounds related to mitoxantrone were prepared. Compounds 4. 1.4-dihydroxy-6-aminoethyl-9.10-anthracenedione was synthesized in 6 steps starting with 4-methyl-phthalic acid, and compound 5, 2(4-aminobutyl)-l 4-dihvdroxv-9,10-anthracenedione was synthesized in 5 steps from N-3-bromopropylphthalimide.     

翼核果中两个微量新化合物及其生物活性

从翼核果的茎中分离得到两个微量新化合物，分别为１，６ 二羟基 ３ 甲基口山酮 ８ 羧基 １ Ｏ β Ｄ 吡喃葡萄糖苷（Ⅰ）及１，６ 二羟基 ３ 甲基口山酮 ８ 羧基 １ Ｏ β Ｄ 吡喃葡萄糖基（１→６） β Ｄ 吡喃葡萄糖苷（Ⅱ）；命名为翼核口山酮苷及翼核口山酮二糖苷．测定了这两个化合物对人慢性髓样白血病细胞Ｋ５６２的抑制生长作用．     

HIV-1蛋白酶解聚型抑制剂的计算机辅助分子设计

目的：探索性研究和设计HIV-1蛋白酶新型抑制剂—解聚型抑制剂。方法：计算机辅助药物设计的分子对接方法。结果：设计的一系列拟肽分子既可阻挠HIV-1 PR二聚体的组装,又可抑制酶的活性。其中,PP30可作为候选先导物。结论：解聚型抑制剂有望抑制突变的HIV-1 PR。     

翼核果中的新化合物

从翼核果的根茎中分离得到一个新化合物，用ＵＶ，ＩＲ，ＭＳ，１Ｈ－ＮＭＲ，１３Ｃ－ＮＭＲ，ＨＭＢＣ，ＤＥＰＴ及１３Ｃ－１ＨＣＯＳＹ光谱进行了测定，鉴定其结构为１，６－二羟基－３－甲基口山酮－８－羧酸－１－Ｏ－β－Ｄ－葡萄糖苷，命名为翼核口山酮苷．     

Effect of bile acids on the binding of drugs and dyes to human albumin

Chenodeoxycholic, cholic, deoxycholic and taurodeoxycholic acids were found to inhibit the binding of 2-(4'-hydroxybenzeneazo)benzoic acid, methyl orange, sulphadimethoxine and warfarin to human albumin. In addition, glycodeoxycholic acid inhibited the binding of sulphadimethoxine and warfarin. In contrast, these bile acids did not inhibit the binding of phenylbutazone. The extent of displacement was in the rank order of: dihydroxy acids (chenodeoxycholic and deoxycholic) greater than trihydroxy acid (cholic) greater than conjugates (glycodeoxycholic and taurodeoxycholic). Thus the introduction of polar groups into the steroid nucleus of bile acids reduces their effectiveness as binding inhibitors. Displacement was usually accompanied by a decrease in the apparent association constant which suggests that the mechanism of displacement may be competitive.     

Metabolism of a novel CCK-B antagonist in rat,dog and human liver microsomes

1. The in vitro metabolism of a novel CCK-B antagonist ((+)-N-[1-adamantane-1- methyl)-2,4-dioxo-5-phenyl-2,3,4,5-tetrahydro-1H-1,5-benzodiazepin-3-yl]N′-phenylurea; GV150013X) was investigated using rat, dog and human liver microsomes. 2. Four monohydroxy and four dihydroxy metabolites of GV150013X in rat and man were identified by comparison with authentic standards using HPLC and mass spectrometry. 3. The dihydroxy metabolite M1 was not detected in dog liver microsomes mixtures. 4. The formation of dihydroxylated metabolites proceeds via monohydroxylated metabolites M5 and M8 and not directly from GV150013X. 5. A monohydroxy metabolite M5 was the major metabolite in rat and dog, with M5 and dihydroxy metabolites M2 and M3 major metabolites in man.     

益智仁的化学成分研究

目的研究益智仁的化学成分。方法用硅胶柱、Sephadex LH-20、高效液相色谱法进行分离纯化,依据理化性质和光谱数据鉴定化合物结构。结果从益智仁的95%乙醇提取物中分离鉴定了10个化合物,分别为:7-表-香科酮(1)、11S-nootkatone-11,12-diol(2)、4S-isoprophy-6-methyl-1-tetralone(3)、香草酸(vanillic acid,4)、3,5-二羟基-4-甲氧基苯甲酸(3,5-dihydroxy-4-methoxybenzoic acid,5)、益智酮甲(yakuchinone A,6)、杨芽黄素(tectochrysin,7)、良姜素(izalpinia,8)、β-谷甾醇(β-sitosterol,9)和胡萝卜苷(daucosterol,10)。结论化合物1⁵为首次从益智仁中分离得到。     

Identification of CYP isozymes involved in benzbromarone metabolism in human liver microsomes

Benzbromarone (BBR) is metabolized to 1′‐hydroxy BBR and 6‐hydroxy BBR in the liver. 6‐Hydroxy BBR is further metabolized to 5,6‐dihydroxy BBR. The aim of this study was to identify the CYP isozymes involved in the metabolism of BBR to 1′‐hydroxy BBR and 6‐hydroxy BBR and in the metabolism of 6‐hydroxy BBR to 5,6‐dihydroxy BBR in human liver microsomes. Among 11 recombinant P450 isozymes examined, CYP3A4 showed the highest formation rate of 1′‐hydroxy BBR. The formation rate of 1′‐hydroxy BBR significantly correlated with testosterone 6β‐hydroxylation activity in a panel of 12 human liver microsomes. The formation of 1′‐hydroxy BBR was completely inhibited by ketoconazole in pooled human liver microsomes. On the other hand, the highest formation rate of 6‐hydroxy BBR was found in recombinant CYP2C9. The highest correlation was observed between the formation rate of 6‐hydroxy BBR and diclofenac 4′‐hydroxylation activity in 12 human liver microsomes. The formation of 6‐hydroxy BBR was inhibited by tienilic acid in pooled human liver microsomes. The formation of 5,6‐dihydroxy BBR from 6‐hydroxy BBR was catalysed by recombinant CYP2C9 and CYP1A2. The formation rate of 5,6‐dihydroxy BBR was significantly correlated with diclofenac 4′‐hydroxylation activity and phenacetin O‐deethylation activity in 12 human liver microsomes. The formation of 5,6‐dihydroxy BBR was inhibited with either tienilic acid or α‐naphthoflavone in human liver microsomes. These results suggest that (i) the formation of 1′‐hydroxy BBR and 6‐hydroxy BBR is mainly catalysed by CYP3A4 and CYP2C9, respectively, and (ii) the formation of 5,6‐dihydroxy BBR is catalysed by CYP2C9 and CYP1A2 in human liver microsomes. Copyright © 2012 John Wiley & Sons, Ltd.     

In Vitro Study of Isoflavones and Isoflavans as Potent Inhibitors of Human 12‐ and 15‐Lipoxygenases

In this study, we have investigated 16 isoflavone and isoflavan derivatives as potential inhibitors of human lipoxygenase (platelet 12‐lipoxygenase, reticulocyte 15‐lipoxygenase‐1, and epithelial 15‐lipoxygenase‐2). The flavonoid baicalein, a known lipoxygenase inhibitor, was used as positive control. Four compounds, 6,7‐dihydroxy‐3′‐chloroisoflavone ( 1c ), 7‐hydroxy‐8‐methyl‐4′‐chloroisoflavan ( 5a ), 7,8‐dihydroxy‐4′‐methylisoflavan ( 5b ), and 7,8‐dihydroxy‐3′‐methylisoflavan ( 5c ), were effective inhibitors of 12‐lipoxygenases and 15‐lipoxygenase‐1 with IC₅₀'s <10 μm , while 6,7‐dihydroxy‐4′‐nitroisoflavone ( 1b ) was a selective inhibitor of 12‐lipoxygenases. Docking studies, antioxidant assays, and kinetic measurements were carried out for the three best inhibitors ( 1b , 5b , 5c ). The results showed that a catechol group in ring A is critical for the antioxidant properties of these compounds, and probably essential for their inhibitory activity. Kinetic assays showed that compounds 1b , 5b , and 5c are competitive inhibitors with K_i values in the range of 0.3–3 μm .     

New oxymesterone metabolites in human by gas chromatography‐tandem mass spectrometry and their application for doping control

Oxymesterone (17α‐methyl‐4, 17β‐dihydroxy‐androst‐4‐ene‐3‐one) is one of the anabolic androgenic steroids (AAS) banned by the World Anti‐Doping Agency (WADA). The biotransformation of oxymesterone is performed in vitro by human heptocytes and human urinary metabolic profiles are investigated after single dose of 20 mg to two adult males as well. Cell cultures and urine samples were hydrolyzed by β‐glucuronidase, extracted, and reacted with N‐Methyl‐N‐trimethylsilyltrifluoroacetamide (MSTFA), ammonium iodide (NH₄I), and dithioerythritol. After derivatization, a gas chromatography triple quadruple tandem mass spectrometry (GC‐MS/MS) using full scan and MS/MS modes was applied. The total ion chromatographs of the blank and the positive samples are compared, and 7 new metabolites were found. In addition to the well‐known 17‐epioxymesterone, oxymesterone is metabolized by 4‐ene‐reduction, 3‐keto‐reduction, 11β‐hydroxylation, and 16ξ‐hydroxylation. Based on the behavior of the MS/MS results of product ion and precursor ion modes, a GC‐MS/MS method has been developed monitoring these metabolites. The structures of metabolite 2 and 4 are tentatively identified as 17α‐methyl‐3β, 17β‐dihydroxy‐5α‐androstane‐4‐one and 17α‐methyl‐3α, 4ξ, 17β‐trihydroxy‐5α‐androstane, respectively. Detection of oxymesterone using new metabolites M2 and M4 can extend the detection window up to 4 days since the parent steroid was not detectable. Copyright © 2015 John Wiley & Sons, Ltd.