二鼠李糖脂5衍生化合物7和鼠李糖脂5以细胞壁为作用靶点的抗菌作用机制

目的 研究新化合物二鼠李糖脂衍生化合物7(DDC7)和鼠李糖脂(C5)抗革兰阳性球菌的作用机制.方法 分离纯化金黄色葡萄球菌ATCC29213细胞壁并用透射电镜观察.依据新化合物对ATCC29213已知的最低抑菌浓度(MIC)结果,用肉汤二倍稀释法,检测新化合物加入不同浓度细胞壁后对ATCC29213的MIC.结果 新化合物DDC7、C5对ATCC29213的MIC为16μg· mL-1.当加入细胞壁浓度≥32 μg·mL-1,可以阻断DDC7、C5分别对ATCC29213的抑菌作用.结论 糖脂新类化合物抗菌作用部位在革兰阳性球菌细胞壁上.     

新糖脂类化合物抗菌活性及其作用机制

目的 利用革兰阳性球菌原型与L型的结构差异,研究新糖脂类化合物抗菌作用部位.方法 用肉汤二倍稀释法,测定糖脂类新化合物对金黄色葡萄菌L型的抗菌活性.结果 在体外,新化合物二鼠李糖脂衍生化合物7和鼠李糖脂cleistrioside-5对甲氧西林耐药和敏感的葡萄球菌、万古霉素耐药和敏感的肠球菌等革兰阳性球菌具有一定抗菌活性;但对革兰阴性杆菌没有抗菌活性,对金黄色葡萄球菌L型亦没有抗菌活性.结论 糖脂类新化合物的作用部位可能为革兰阳性球菌的细胞壁.     

扬子毛茛中的化学成分研究

目的研究扬子毛茛的化学成分.方法应用多种色谱方法和色谱材料进行提取、分离和纯化,用各种现代光谱方法并结合文献对分得的化合物进行结构解析.结果从扬子毛茛的95%乙醇提取物中分到十三个化合物,其中五个为黄酮苷类化合物,分别命名为芹菜素-4'-O-α-L-鼠李糖苷(1),芹菜素-7-O-β-D-葡萄糖苷-4'-O-α-L-鼠李糖苷(2),芹菜素-8-C-α-L-阿拉伯糖苷(3),芹菜素-8-C-β-D-半乳糖苷(4),小麦黄素-7-O-β-D-葡萄糖苷(5);其余八个分别为小麦黄素(6),木犀草素(7),东莨菪内酯(8),秦皮乙素(9),滨蒿内酯(10),阿魏酸(11),原儿茶酸(12)和小毛茛内酯(13).此外还对这些化合物的体外抗癌活性进行了初步的测试.结论化合物1-12为首次从该属植物中分到,化合物13为首次从该种植物中分到,其中化合物1为新的天然产物,化合物2和3首次报道了其碳谱数据.生物活性测试结果表明化合物1对BEL-7407及A549细胞的IC50值分别为43及77μg·mL-1,化合物8和10对KB细胞的IC50分别为78和44μg·mL-1,对HL-60细胞的IC50均为85μg·mL-1.化合物7对所测试的四种肿瘤细胞株均显示一定的细胞毒活性,其对KB,BEL-7407,A549及HL-60细胞的IC50分别为51,55,44和10μg·mL-1.     

达托霉素可有效治疗MRSA和GISA引起的实验性心内膜炎

脂肽类抗生素达托霉素对革兰阳性球菌具有体外活性。该研究评估了达托霉素对临床分离株MRSA277（万古霉素的MIC为2μg／mL）和糖肽类中介金黄色葡萄球菌（6ISA）ATCC700788（万古霉素的MIC为8μg／mL）的体内外活性。时间-杀菌试验证明,在体外,达托霉素对此2菌株均有抗菌活性;     

金钱草中黄酮苷的分离与结构鉴定

目的从金钱草中分离制备标准品.方法用硅胶柱色谱进行分离,通过理化方法及IR,UV,MS,1HNMR,13CNMR,DEPT,HMQC,HMBC等光谱分析确定化合物结构.结果从金钱草中分离得到2个化合物,分别鉴定为鼠李酮酸γ-内酯(I)、山奈酚-3-O-α-L-鼠李糖(1→2)-β-D-木糖苷(II).结论 II为新化合物,命名为金钱草素,I为首次从该属植物中分离得到.     

用小分子化合物使耐药菌对万古霉素重新敏感

病原性肠球菌正在对目前临床使用的抗生素产生耐药性 ,包括对万古霉素 (1)这一作为抗革兰阳性菌感染的最后一线药物。细菌对 1的抗性主要是由于构成细菌细胞壁的肽聚糖的前体的末端发生改变 ,使其不能结合 1而导致细菌耐药。研究发现一些有定向性亲核、亲电基团并与肽聚糖末端手性互补的小分子 ,能有选择性地催化肽聚糖前体缩酚肽(depsipeptide)的裂解。据此设计了一些小分子化合物 ,其中有代表性的是 Spro C5。与 1联合用药的试验表明 ,它能将一株耐 1的肠球菌的最低抑菌浓度从 5 0 0 μg/m l降到 6 2 .5 μg/m l。这种能使耐药菌对 1重新…     

青天葵中鼠李柠檬素在大鼠体内的药代动力学研究

目的 研究青天葵中鼠李柠檬素在大鼠体内的药代动力学特征.方法以甲醇一乙腈-0.2％磷酸水溶液（30∶35∶35）为流动相,血浆样品经10％三氯乙酸沉淀蛋白后,采用高效液相色谱法测定鼠李柠檬素的血药浓度.采用DAS 2.1.1药代动力学软件计算鼠李柠檬素的主要药代动力学参数.结果 鼠李柠檬素质量浓度在0.05～10.00 μg/mL范围内与峰面积线性关系良好（r=0.9993）,回收率为98.1％ ～ 101.1％,日内和日间RSD均小于11％.鼠李柠檬素大鼠体内符合二室模型,主要药代动力学参数峰浓度（Cmax）为（875.37±65.53）μg/L,药物消除半衰期（t1/2β）为（8.993±2.568）h,0 ～24h药时曲线下面积（AUC0-24）为（4929.159±589.652）μg· h/L,0～∞药时曲线下面积（AUC0-x）为（5 945.567±612.985）μg·h/L.结论鼠李柠檬素的药代动力学研究结果为青天葵药材的质量评价奠定了良好基础.     

苯唑西林诱导金黄色葡萄球菌形成L型研究

目的 用苯唑西林(青霉素类抗生素)诱导金黄色葡萄球菌形成L型.方法 用抗生素诱导法(液体法),用高渗培养进行金黄色葡萄球菌L型的诱导,用含药平板法进行细菌L型的筛选及菌落计数.对细菌L型的培养物进行革兰和细胞壁染色;对金黄色葡萄球菌原型及回复型菌进行MIC测定.结果 与结论苯唑西林在50μg·mL-1时,可诱导金黄色葡萄球菌形成L型.     

巴东过路黄酚类化学成分研究

为了研究巴东过路黄的化学成分,采用硅胶、ODS、MCI以及Sephadex LH-20等柱色谱方法从巴东过路黄95%乙醇提取物中分离得到12个酚类成分,根据化合物的波谱数据分别鉴定为槲皮素-3-O-α-L-鼠李糖-3’-O-α-L-鼠李糖苷(1)、杨梅苷(2)、槲皮苷(3)、芦丁(4)、2-hydroxynaringenin-4’-O-glucopyranoside(5)、柚皮素-7-O-葡萄糖苷(6)、芹糖甘草苷(7)、甘草查尔酮B(8)、tetrahydroxymethoxychalcone(9)、对羟基肉桂酸甲酯(10)、2,4,6-trihydroxyacetophenone 2-O-glucopyranoside(11)和vaccihein A(12)。化合物1为新化合物,化合物5、11、12为首次从珍珠菜属植物中分离得到,其余化合物为首次从该植物中分离得到。     

仙人掌中一个新α-吡喃酮成分的分离与结构鉴定

目的　研究仙人掌的化学成分。方法　应用多种柱色谱方法进行分离和纯化 ,NMR和MS等波谱解析化学结构。结果　从仙人掌肉质茎的乙醇提取物中分离出 6个化合物 ,其结构分别鉴定为 :3 O 甲基异鼠李黄素 (1)、4 乙氧基 6 羟甲基 α 吡喃酮 (2 )、正十七醇 (3)、香草酸 (4)、异鼠李黄素 3 O 鼠李糖苷 (5 )和芦丁 (6 )。结论　化合物2为新化合物 ,化合物 1、3、4、5均为首次从本属植物中分离得到 ,化合物 6为本植物首次分离得到。     

Synthesis of some benzimidazole derivatives and their antibacterial and antifungal activities.

A number of new benzimidazole derivatives were synthesized by the reaction of benzimidazole with appropriate alkyl halides. The compounds synthesized were intensified by 1H-NMR, Fourier Transformation Infrared (FT-IR) and micro analysis. All new and related compounds studied in this work were screened for their in vitro antimicrobial activities against the standard strains: Enterococcus faecalis (ATCC 29212), Staphylococcus aureus (ATCC 29213), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853) and the yeasts Candida albicans and Candida tropicalis. Eleven of the compounds were found effective to inhibit the growth of Gram-positive bacteria (E. faecalis and S. aureus) at MIC values between 12.5-400 micrograms/ml. None of the compounds exhibited antimicrobial activity against Gram-negative bacteria (E. coli and P. aeruginosa) at the concentrations studied (6.25-800 micrograms/ml). All compounds (except compound 3) were significantly effective against C. tropicalis with MIC values of 6.25-400 micrograms/ml. Eight of the tested compounds showed an antifungal activity against C. albicans with a range of the MICs between 50 and 400 micrograms/ml.     

应用蒙特卡罗模拟优化肾功能不全患者肠球菌感染时万古霉素的给药方案

目的:根据抗菌药物PK/PD理论,采用蒙特卡罗模拟的手段,对肾功能不全患者万古霉素治疗肠球菌感染的给药方案进行优化。方法:收集已发表的万古霉素的药动学资料和我院万古霉素对粪肠球菌和屎肠球菌的MIC分布数据;设置AUC24h/MIC>400,利用Crystal Ball软件模拟出5 000个患者的PTA和CFR。结果:万古霉素能达到满意抗菌活性的最低剂量:对于肌酐清除率>80 mL.min-1的患者(A组),当MIC=0.5μg.mL-1时,给予万古霉素1 500 mg.d-1;当MIC=1μg.mL-1时,给予万古霉素2 500 mg.d-1。对于肌酐清除率在50～80 mL.min-1的患者,当MIC=0.5μg.mL-1时,给予万古霉素1 000 mg.d-1,当MIC=1μg.mL-1时,给予万古霉素2 000 mg.d-1。对于肌酐清除率在10～50 mL.min-1的患者,只有在MIC=0.5μg.mL-1时给予750 mg.d-1,才能达到满意的抗菌活性。结论:蒙特卡罗模拟法把药动学和药效学结合起来,既考虑了不同个体对药物处置的差异性,又考虑了病原菌耐药性的差异,这样获得的给药方案将更合理,也更能提高临床治疗效果。     

Synthesis and In Vitro Antibacterial Activity of 7‐(3‐Alkoxyimino‐4‐methyl‐4‐methylaminopiperidin‐1‐yl)‐fluoroquinolone Derivatives

A series of novel 7‐(3‐alkoxyimino‐4‐methyl‐4‐methylaminopiperidin‐1‐yl)fluoroquinolone derivatives were designed, synthesized, and characterized by ¹H‐NMR, MS, and HRMS. These fluoroquinolones were evaluated for their in‐vitro antibacterial activity against representative Gram‐positive and Gram‐negative strains. Generally, all of the target compounds have considerable antibacterial activity against the tested forty strains, and exhibit exceptional potency in inhibiting the growth of methicillin‐sensitive Staphylococcus aureus (MSSA) and methicillin‐resistant S. aureus (MRSA) ATCC33591 (MICs: 0.06 to 2 μg/mL). In particular, compounds 14 , 19 , 28 , and 29 are fourfold more potent than ciprofloxacin against MSSA 08‐49. Compounds 23 , 26 , and 27 are twofold more potent than ciprofloxacin against MRSA ATCC33591 and MSSA ATCC29213. In addition, compound 14 exhibits excellent activity (MIC: 0.06 μg/mL) against Acinetobactes calcoaceticus, which is two‐ to 16‐fold more potent than the reference drugs gemifloxacin, levofloxacin, and ciprofloxacin.     

应用蒙特卡罗模拟优化肾功能不全患者MRSA感染时万古霉素的给药方案

目的:根据抗菌药物PK/PD理论,采用蒙特卡罗模拟的手段,对肾功能不全患者万古霉素的给药方案进行优化。方法:收集已发表的万古霉素的药代动力学资料和我院万古霉素对甲氧西林耐药金黄色葡萄球菌(MRSA)的MIC分布数据;设置AUC24 h/MIC>400,利用Crystal Ball软件模拟出5 000例患者的PTA和CFR。并与临床病例进行对照。结果:万古霉素能达到满意抗菌活性的最低剂量:对于肌酐清除率>80 mL.min-1的患者(A组),当MIC=0.5μg.mL-1时,给予万古霉素1 500 mg.d-1;当MIC=1μg.mL-1时,给予万古霉素2 500 mg.d-1;当MIC=2或4μg.mL-1时,即使给予万古霉素4 000 mg.d-1,也不能达到满意的抗菌活性。对于肌酐清除率在50～80 mL.min-1的患者,当MIC=0.5μg.mL-1时,给予万古霉素1 000mg.d-1,当MIC=1μg.mL-1时,给予万古霉素2 000 mg.d-1;当MIC=2或4μg.mL-1时,即使给予万古霉素2 000 mg.d-1,也不能达到满意的抗菌活性。对于肌酐清除率在10～50 mL.min-1的患者,只有在MIC=0.5μg.mL-1时给予750 mg.d-1,才能达到满意的抗菌活性;对于健康志愿者,当MIC=0.5μg.mL-1时,给予万古霉素2 000 mg.d-1,能达到满意的抗菌活性。临床结果与模拟结果基本一致。结论:蒙特卡罗模拟法把药代动力学和药效学结合起来,既考虑了不同个体对药物处置的差异性,又考虑了病原菌耐药性的差异,这样获得的给药方案将更合理,也更能提高临床治疗效果。     

具有手性吡咯烷侧环的噁唑烷酮类化合物的合成及抗菌活性研究

目的 设计合成具有手性吡咯烷侧环的噁唑烷酮类化合物,并考察其体外抗菌活性。方法 以手性脯氨酸和3,4-二氟硝基苯为原料,通过多步反应合成目标化合物;采用微量液体稀释法检测目标化合物的抗菌活性。结果与结论 合成了 8 个新化合物,其结构经 ¹H-NMR、MS 谱确证。体外活性试验表明：由（R）-脯氨酸衍生的化合物7b 对革兰阳性菌[金黄色葡萄球菌、表皮葡萄球菌以及耐甲氧西林金黄色葡萄球菌（MRSA）具有良好的抑制活性,对革兰阴性菌具有较弱的抑制活性。由（S）-脯氨酸衍生的化合物 7a 的抗菌活性明显低于 7b。研究结果表明,吡咯烷侧环的手性因素对抗菌活性具有显著影响。     

Synthesis and evaluation of analgesic/ anti-inflammatory and antimicrobial activities of 3-substituted- 1,2,4-triazole-5-thiones

In this study, the synthesis of a novel series of Mannich bases of 5-mercapto-3-aryl-1,2,4-triazoles is described. The structures attributed to compounds la-5e were elucidated using IR and 1H-NMR spectroscopic techniques besides elemental analysis. The formation of 1-aminomethyl-3-substituted-1,2,4-triazole-5-thiones - not the isomeric 3-substituted-4-aminomethyl-1,2,4-triazole-5-thiones was unambiguously confirmed by X-ray crystallographic analysis of 1c. The compounds were examined for their in vivo anti-inflammatory and analgesic activity in two different bioassays, namely carrageenan-induced hind paw edema and p-benzoquinone-induced abdominal constriction tests in mice, respectively. In addition, the ulcerogenic effects of the compounds were determined. Among the tested derivatives most promising results were obtained for the compounds bearing a nonsubstituted phenyl group at C-3 position of the triazole ring (1a-e). The compounds were also evaluated for their in vitro antimicrobial activity against a series of gram positive bacteria [Staphylococcus aureus (ATCC 29213), Enterococcus faecalis (ATCC 29212)], gram negative bacteria [Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853)] and yeast-like microorganisms [Candida albicans (ATCC 90028), C. krusei (ATCC 6258), C. parapsilosis (ATCC 22019)]. One series of the examined compounds (3a-e) exhibited better antibacterial activity especially against gram positive bacteria than against gram negative bacteria. Compounds 2c, 3b, and 3e were found to be more effective against C. parapsilosis compared with the other derivatives (MIC: 16 microg/mL).     

Antibacterial and antifungal activities of complexes of ruthenium (II).

Twenty ruthenium (II) complexes (1-5) were evaluated for their in vitro antibacterial and antifungal activity against Enterococcus faecalis (ATCC 29212), Staphylococcus aureus (ATCC 29213), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), Candida albicans and Candida tropicalis. Compounds 1d, 1e, 1h, 1i and 1j showed more pronounced antimicrobial activity against Gram-positive bacteria and fungi as compared to the nitrogen donor ruthenium complexes; hydrophobic substituents were significantly more effective. None of the compounds 1-5 exhibited antimicrobial activity against the Gram-negative strains Escherichia coli (ATCC 25922) and Pseudomonas aeruginosa (ATCC 27853) with the concentrations ranging between 12.5 and 800 micrograms/ml.     

3-硝基-2H-色烯衍生物的合成及抗菌活性研究

目的设计并合成一系列3-硝基-2H-色烯衍生物,研究其抗菌活性与构效关系。方法以水杨醛和2-硝基乙醇为原料合成目标化合物,采用肉汤稀释法测定抗菌活性。结果目标化合物结构均经过1HNMR和HRMS确证,3-硝基-2H-色烯衍生物对金黄色葡萄球菌、耐甲氧西林金黄色葡萄球菌具有很好的抑制活性(MIC=4μg·mL-1)。结论 3-硝基-2H-色烯衍生物具有进一步深入研究的价值。     

Synthesis,antibacterial and antifungal activities of electron-rich olefins derived benzimidazole compounds

New benzimidazole derivatives were synthesised by electron-rich olefines (7, 8 and 9) with appropriate reagents. The compounds synthesised were identified by 1H NMR, 13C NMR, FT-IR spectroscopic techniques and elemental analysis. All compounds studied in this work were screened for their in vitro antimicrobial activities against the standard strains: Enterococcus faecalis (ATCC 29212), Staphylococcus aureus (ATCC 29213), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853) and the yeasts Candida albicans and Candida tropicalis. Eleven of the compounds inhibited the growth of gram-positive bacteria (E. faecalis and S. aureus) at MIC values between 50 and 400 microg/ml. None of the compounds exhibit antimicrobial activity against Gram-negative bacteria (E. coli and P. Aeruginosa) at the concentrations studied (6.25-800 microg/ml). Nine of the tested compounds showed an antifungal activity with a range of the MICs between 50 and 400 microg/ml.     

3-羟基-6-O-甲基红霉素-9-肟基衍生物的合成及体外抗菌活性

目的　寻找并合成抗耐药菌活性的3位羟基红霉素衍生物。方法　以红霉素A为原料,经9位酮基肟化,9位肟羟基,2′位羟基和3′位二甲胺基同时苄基化,6位羟基甲基化,水解去3位克拉定糖,氢化还原脱苄基,对甲基苄基或邻氯苄基取代9位肟羟基等6步反应,制得3-羟基-6-O-甲基红霉素-9-肟基衍生物,其结构经¹³CNMR ,FAB MS确证。结果　共制得7个化合物,对其中4个(5 - 8)未见报道的化合物进行了体外抗菌活性测定。结论　5 ,7,8对部分红霉素诱导耐药菌有一定的活性