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。     

土壤真菌07-11号菌株中的酚酸性成分

以稻瘟霉 (Pyriculariaoryzae)分生孢子及菌丝形态变化为指标 ,对从云南土壤中分离得到0 7 1 1真菌的发酵产物中活性成分追踪分离 ,从其乙酸乙酯层浸膏中得到 3个酚酸性成分 ,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 甲基异苯并呋喃酮 (Ⅱ )及 2 甲酰基 3 ,5 二羟基 4 甲基苯甲酸 (Ⅲ ) ,它们对稻瘟霉分生孢子及菌丝体都有一定抑制作用     

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。     

海洋真菌09-1-1-1次级代谢产物的研究

目的从海洋真菌的代谢产物中寻找新的具有抗真菌活性的化合物。方法以稻瘟霉生物模型筛选海洋真菌,获得编号09-1-1-1的活性菌株,从其发酵液中分离活性代谢产物。结果从发酵液中分离到2个化合物,鉴定其结构为3a,12c-二氢-8-羟基-6-甲氧基-7H-呋喃[3′,2′∶4,5]呋喃[2,3-c]呫吨-7-酮(Ⅰ,sterig-matocystin)和1,3,6,8-四羟基-2-(1-羟己基)-9,10-蒽二酮(Ⅱ,averantin)。结论稻瘟霉生物模型用于筛选海洋真菌活性代谢产物成本低、快速又方便。化合物Ⅱ对109稻瘟霉菌丝的生长最小抑制浓度为1.6μg.mL-1。     

北极真菌Nectria sp.B-13中酚醛倍半萜烯类化合物的研究

摘要：目的 对北极真菌 Nectria sp. B-13 中的酚醛倍半萜烯类化合物进行结构鉴定及生物学活性研究。方法 采用硅胶柱层析、Sephadex LH-20凝胶柱层析、高效液相色谱等分离手段对极地真菌Nectria sp. B-13发酵液的乙酸乙酯萃取部位进行了系统的分离,利用1H-和13C-NMR、LC-MS等现代波谱解析手段,结合文献对照,鉴定化合物结构;采用MTT法和微量稀释法测试了化合物的细胞毒活性和抗稻瘟霉作用。结果 从提取物中分离得到6个化合物,其中4个为酚醛倍半萜烯类化合物,分别为dechlorodeacetylchloronectrin（1）,LL-Z-1272 ε acid（2）,8''-hydroxyascochlorin（3）和LL-Z 1272 β（4）,以及邻苯二甲酸丁酯异丁酯（5）和邻苯二甲酸二丁酯（6）。活性测试的结果表明,化合物2对5种肿瘤细胞株均有一定程度的生长抑制作用,其IC50值的范围在48.67~92.18 μM之间;同时,化合物2还可抑制稻瘟霉的生长,MIC值为18.2 μg/mL。结论 化合物1和化合物2为首次从微生物次级代谢产物中获得的化合物,为新天然产物。化合物2有一定的细胞毒活性和抗稻瘟霉作用。     

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     

耐酸青霉菌Penicillium purpurogenum OUCMDZ-019的次级代谢产物研究

目的 对耐酸产紫青霉OUCMDZ-019的次级代谢产物进行化学成分和生物活性研究,发现潜力结构资源。方法 对菌株进行规模发酵得到粗提物,利用常压柱层析、凝胶分子筛以及半制备高效液相等方法进行次级代谢产物的分离纯化;利用现代波谱学方法(核磁共振1D NMR、2D NMR、圆二色谱ECD、旋光等)对化合物进行结构鉴定,并评价其抗病毒生物活性。结果 分离鉴定得到4个单体化合物,(-)-Mitorubrinol (1)、6″-Hydroxy-(R)-mitorubrinic acid (2)、(-)-Mitorubrinic acid (3)、Purpurquinone D (4)。结论 从耐酸真菌产紫青霉OUCMDZ-019的次级代谢产物中分离鉴定得到了化合物1~4,均属于嗜氮酮类化合物,研究获得规模量产化合物3,为后续药物的结构衍生打下基础。     

产黄青霉Penicillium chrysogenum S-3-25人工海水培养基发酵次级代谢产物研究

目的 阐明南极深海来源真菌产黄青霉Penicillium chrysogenum S-3-25人工海水培养基的发酵次级代谢产物及其活性。方法 利用各种色谱技术分离纯化次级代谢产物,根据理化和波谱数据（核磁共振、质谱技术和Marfey分析）鉴定化合物结构,采用3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide（MTT）法评价细胞毒活性。结果 从真菌S-3-25人工海水培养基发酵产物中分离鉴定了8个单体化合物：2-[[(2S)-2-amino-1-oxopropyl] amino] benzoic acid (1),methyl 2-[[(2S)-2-amino-1-oxopropyl] amino] benzoate (2),2-[[(2S)-2-hydroxy-1-oxopropyl] amino] benzamide (3),3-(p-hydroxyphenyl)-N-methylpropionamide (4),4-hydroxycinnamamide (5),cyclo-(L-Pro-L-Tyr) (6),脑苷脂A (7) 及脑苷脂B (8)。细胞毒活性测试结果表明化合物1~8在50 μM作用浓度下对三种受试细胞（人乳腺癌MCF-7,人肺癌A549以及小鼠小胶质BV2细胞）的抑制率均低于50%。结论 从极地深海来源真菌产黄青霉S-3-25人工海水培养基发酵产物中分离得到8个单体化合物,其中化合物1和2为新天然产物,未见有文献数据的报道。化合物1~8均未呈现较强的细胞毒活性。     

黑团孢霉次生代谢产物化学成分研究

摘要：目的:研究黑团孢霉次生代谢产物的化学成分。方法:采用硅胶柱色谱法、凝胶柱色谱法、半制备高效液相色谱法等分离方法和技术对黑团孢霉次生代谢产物的化学成分进行分离纯化,使用核磁数据分析鉴定化合物的结构。结果:从黑团孢霉次生代谢产物中分离得到4个化合物,分别鉴定为dankasterone B（1）、cyathiserone（2）、herbarulide（3）、demethylincisterol A2（4）。结论:化合物1～4均为首次从黑团孢霉中分离得到。     

Urinary tract infection in geriatric patients

Elderly patients with urinary tract infection (UTI) are believed less likely to be cured by antimicrobial therapy than younger patients. The reasons for this poorer outcome have not yet been clarified. We have investigated the effect of antimicrobial therapy in elderly patients with complicated UTI. Four-hundred and eighty patients, 244 men and 236 women, who had complicated UTI (266 symptomatic and 236 asymptomatic) and were 20–79 years of age, were treated with one of three different drugs; one was a newer quinolone and two were oral cephems. Multivariate logistic regression analysis of treatment outcome revealed that the clinical response was significantly related to general underlying diseases and diseases of the urinary tract, but not to age, symptomatic or asymptomatic UTI, or infection site such as the kidney or bladder. We concluded that the clinical effectiveness of an antimicrobial agent was not directly related to age, and that urological examination for underlying diseases and control of them is quite important for effective treatment and control of complicated UTIs, especially in elderly patients.     

2，3-二氢喹啉-4（1H）-酮缩氨基脲类化合物的设计、合成及抗真菌活性研究

目的合成一系列二氯-2,3-二氢喹啉4（1H）-酮缩氨基脲类化合物并测定其体外抗真菌活性。方法以二氯苯胺和丙烯酸为起始原料,经加成、环合制得中间体5,7-二氯-2,3-二氢喹啉-4（1H）-酮和6,8-二氯-2,3-二氨喹啉-4（1H）-酮;中间体与各种胪-取代的氨基脲缩合得到目标化合物;采用二倍浓度稀释法测试各目标化合物的体外抗真菌活性,实验选用9种临床上常见的致病真菌为测试菌株,以氟康唑为阳性对照药。结果与结论合成的24个化合物均未见文献报道,其结构经。H-NMR、Ms谱确证;活性测试结果表明,多个目标化合物对测试真菌表现出较好的体外抑菌活性。     

Pharmacokinetics and tissue distribution of 3-((5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl)methyl)benzamide; a novel ALK5 inhibitor and a potential anti-fibrosis drug

The authors investigated the pharmacokinetics and metabolism of 3-((5-(6-methylpyridin-2-yl)-4-(quinoxalin-6-yl)-1H-imidazol-2-yl)methyl)benzamide (IN-1130), a novel ALK5 inhibitor, which suppresses renal and hepatic fibrosis, and also exerts anti-metastatic effects on breast cancer-bearing MMTV-cNeu mice model. Plasma half-lives of orally administered IN-1130 were 62.6 min in mice, 76.6?±?10.6 min in dogs, 156.1?±?19.3 min in rats, and 159.9?±?59.9 min in monkeys. IN-1130 showed a high apparent permeability coefficient (P_app) of (45.0?±?2.3)?×?10^?6 cm s^?1 in in vitro permeability tests in a Caco-2 cell monolayer model. The bioavailability of orally administered IN-1130 was 84.9% in dogs and 34.4% in monkeys (oral dose, 5.5 mg kg^?1), 11.4% in rats and 8.95% in mice (oral dose, 50.3 mg kg^?1), respectively. Orally given IN-1130 was readily distributed into liver, kidneys and lungs. The major metabolite of IN-1130 (M1) was detected in the systemic circulation of rat and mouse and was purified and tentatively identified as 3-((4-(3-hydroxyquinoxaline-6-yl)-5-(6-methylpyridine-2-yl)-1H-imidazol-2-yl)methyl)benzamide or 3-((4-(2-hydroxyquinoxalin-6-yl)-5-(6-methylpyridine-2-yl)-1H-imidazol-2-yl)methyl)benzamide. The highest levels of M1 were found in liver. The results of this study suggest that IN-1130 has the potential to serve as an effective oral anti-fibrotic drug.     

Evidence that 2-phenylpyrazolo[4,3-c]-quinolin-3(5H)-one antagonises pharmacological, electrophysiological and biochemical effects of diazepam in rats

The effects of the acute administration of 2-phenylpyrazolo[4,3-c]quinolin-3(5H)-one on diazepam-induced behaviour and electrophysiological activity were studied in rat. The compound, in doses of 5-10 mg/kg (i.p.), which per se did not induce alterations in spontaneous locomotor activity, antagonised the sedative effect induced by 5-10 mg/kg (i.p.) of diazepam. The injection of diazepam in rats, induced a profound reduction in the first negative wave of the recording of the visual evoked potential used as a sensitive electrophysiological test, in vivo. 2-Phenylpyrazolo[4,3-c]quinolin-3(5H)-one (10 mg/kg, i.p.) caused a recovery of the amplitude of the first negative wave within a few minutes. This result was confirmed by the finding that 2-phenylpyrazolo[4,3-c]quinolin-3(5H)-one, injected acutely in rats, pretreated with diazepam exhibited the capacity to antagonise the binding of [3H]diazepam determined in vitro on synaptic membrane preparations from cortex. The comparison of the pattern of the visual-evoked potential, recorded after the injection of 2-phenylpyrazolo[4,3-c]quinolin-3(5H)-one (50 mg/kg) with the patterns recorded after the injection of ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-imidazolo(1,5a) (1,4)benzodiazepine-3-carboxylate (50 mg/kg) and ethyl-beta-carboline-3-carboxylate and 1-methyl-beta-carboline demonstrated that 2-phenylpyrazolo[4,3-c]quinolin-3(5H)-one is devoid of intrinsic activity.     

抗肿瘤药物2，3－二乙酰氧基－5－烷氧羰基－1－（3′，5′－二酮－N（4′）－取代哌嗪甲基）苯的合成研究（Ⅲ）

在寻找新型抗肿瘤药物过程中，作者设计并合成了十四个３．５－哌嗪二酮类化合物。经过对肿瘤细胞Ｐ３８８体外试验结果表明，化合物（Ⅲ１，Ⅲ５，Ⅲ７）活性较高，其他化合物也只有一定的生物活性．（Ⅲ１：剂量：１γ／ｍＬ，抑制率：５０％：Ⅲ５：剂量：１γ／ｍＬ，抑制率：７３％；Ⅲ７：剂量：１γ／ｍＬ，抑制率：７２％）     

Enantioselective synthesis of tri-deuterated (–)-geosmin to be used as internal standard in quantitation assays

For the accurate and sensitive quantitation of the off-flavor compound geosmin, particularly in complex matrices, a stable isotopologue as internal standard is highly advantageous. In this work, we present a versatile synthetic strategy leading from (4aR)-1,4a-dimethyl-4,4a,5,6,7,8-hexahydronaphthalen-2(3H)-one to tri-deuterated (–)-geosmin ((4S,4aS,8aR)-4,8a-dimethyl(3,3,4-²H₃)octahydronaphthalen-4a(2H)-ol). The starting material was readily accessible from inexpensive 2-methylcyclohexan-1-one using previously published procedures.     

A novel sulphur glycoside from the seeds of Descurainia sophia (L.)

A new sulphur glycoside, named descurainoside (1), and the known compound sinapic acid (2) have been isolated from the seeds of Descurainia sophia (L.) Webb ex Prantl. The structure of 1 has been identified as (1R,6S,8R,9S,10S)-9,10-dihydroxy-4-[(4-hydroxy-3,5-dimethoxyphenyl)methylene]-8-(hydroxymethyl)-2,7-dioxa-5-thiabicyclo[4.4.0]decan-3-one by means of physico-chemical properties and spectroscopic methods (1D and 2D NMR, HRMS, ESI-MS).     

A novel sulphur glycoside from the seeds of Descurainia sophia (L.)

A new sulphur glycoside, named descurainoside (1), and the known compound sinapic acid (2) have been isolated from the seeds of Descurainia sophia (L.) Webb ex Prantl. The structure of 1 has been identified as (1R,6S,8R,9S,10S)-9,10-dihydroxy-4-[(4-hydroxy-3,5-dimethoxyphenyl)methylene]-8-(hydroxymethyl)-2,7-dioxa-5-thiabicyclo[4.4.0]decan-3-one by means of physico-chemical properties and spectroscopic methods (1D and 2D NMR, HRMS, ESI-MS).     

2′,4′-二氯苯基哒嗪衍生物的抗小鼠癫痫作用

本文对2′,4′-二氯苯基哒嗪衍生物对几种实验性癫痫模型的对抗作用进行了研究,其中化合物Ⅰ和Ⅱ对最大电休克发作实验(MEST),戊四唑(Met)印防己毒素发作和荷包牡丹碱发作等四种实验性癫痫模型均有很强的对抗作用,强于苯妥英钠,苯巴比妥和卡马西平,但也显示中枢抑制作用,预防指数不高,化合物Ⅲ和Ⅳ对这四种动物惊厥模型亦有较强的对抗作用,均大大强于丙戊酸钠和乙琥胺,其中化合物Ⅲ的中枢神经系统毒性较低,抗MEST的预防指数高达23.4.     

（1S,4S）—2—甲基—2,5—二氮杂二环[2.2.1]庚烷的合成

以反－４－羟－Ｌ－脯氨酸为原料,以硼氢化锌还原羧基,以二甲基甲酰胺代替吡啶在室温下进行羟基磺酰化,在甲胺水－甲苯溶液中取代环合,共经５步合成（１Ｓ,４Ｓ）－２,５－二氮杂二环「２．２．１」庚烷,５步总收率３７％。