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。     

泰能的体外抗菌活性试验

目的:考察泰能(亚胺培南/西司他丁)的体外抗茵活性.方法:采用琼脂二倍稀释法测定泰能和其他3种药物对136株临床分离茵的体外抗茵活性.结果:泰能对金黄色葡萄球茵、绿脓杆菌、大肠杆菌、肺炎克雷伯氏茵、表皮葡萄球菌、β-溶血性链球菌、阴沟肠杆菌和微球菌的抗茵活性优于海舒必、他唑西林和头孢他啶,对肺炎球菌的抗茵活性较海舒必和头孢他啶弱.结论:泰能对本试验中所有的受试菌有较强的抗茵活性.     

116株铜绿假单胞茵的耐药性分析

目的 分析铜绿假单胞茵耐药机制及现状,指导临床合理应用抗茵药物.方法 用K-B纸片扩散法对116株铜绿假单胞茵做13种抗菌药物的敏感试验,并对70铜绿假单胞茵进行了超广谱β-内酰胺酶(ESBLs)的测定.结果 对13种抗菌药物的敏感试验显示,铜绿假单胞菌对β-内酰胺类抗生素显示较高耐药,对氨基苷类、喹诺酮类等也有不同程度的耐药,而碳青霉烯类有很高的抗茵活性.结论 铜绿假单胞菌对临床常用的抗茵药物呈高耐和多重耐药,其耐药机制为β-内酰胺酶的产生(ESBLs、AmpC酶),环丙沙星、左氧氟沙星、头孢吡肟等可作为治疗其感染的首选用药,亚胺培南可作为二线用药,治疗其混合感染及其高耐菌株.     

常见革兰氏阴性菌耐药性动态变化特征及分析

目的 分析本地区2003年1月～2006年6月期间最常见革兰氏阴性茵(大肠埃希茵、肺炎克雷伯菌、铜绿假单胞菌和鲍曼不动杆菌)耐药性的变化,为指导临床合理使用抗菌素提供可靠依据.方法 应用回顾性调查分析方法对我院该期间临床标本分离的大肠埃希菌、肺炎克雷伯菌、铜绿假单胞菌和鲍曼不动杆菌的药敏试验进行对比统计分析.结果 近4年来,该4种细菌对常用抗菌药物的耐药率总体呈上升趋势.大肠埃希茵对头孢呋辛、头孢他啶、头孢噻肟、头孢吡肟耐药率变化显著,对大肠埃希茵保持较强抗茵活性而耐药率＜30%的抗菌药物有阿莫西林-克拉维酸、哌拉西林-三唑巴坦、亚胺培南、美诺培南、阿米卡星;肺炎克雷伯茵对哌拉西林、替卡西林-克拉维酸、头孢他啶、头孢噻肟、头孢呋辛、环丙沙星耐药率变化显著,对肺炎克雷伯菌保持较强抗菌活性而耐药率＜30%的抗菌药物有阿莫西林-克拉维酸、哌拉西林-三唑巴坦、亚胺培南、美诺培南、阿米卡星、奈替米星、妥布霉素;铜绿假单胞菌对妥布霉素、阿米卡星、庆大霉素、环丙沙星耐药率变化显著,对铜绿假单胞菌保持较强抗菌活性而耐药率＜30%的抗菌药物有替卡西林-克拉维酸、哌拉西林-三唑巴坦、头孢他啶、亚胺培南、美诺培南、阿米卡星、庆大霉素、妥布霉素、环丙沙星、多粘菌素E;对鲍曼不动杆菌保持较强抗茵活性而耐药率＜30%的抗茵药物有哌拉西林-三唑巴坦、头孢他啶、亚胺培南、美诺培南、阿米卡星.结论 本地区大肠埃希菌、肺炎克雷伯茵、铜绿假单胞菌和鲍曼不动杆菌对常用抗菌药物耐药率高,多重耐药现象严重,根据药敏结果选择抗菌药物,可有效控制和减缓细茵耐药性的增长.     

浒苔共生真菌HT-2次生代谢产物的研究

目的探究浒苔共生真菌——蜡叶散囊菌(Eurotium herbariorum)HT-2的次生代谢产物及其抗菌活性。方法菌株规模发酵,有机溶剂萃取,采用硅胶柱色谱、凝胶柱色谱及HPLC等方法对发酵产物进行分离、纯化,运用紫外、红外、核磁共振等手段鉴定化合物的结构;采用二倍稀释法评价化合物的抑菌活性。结果从浒苔共生真菌E.herbariorum HT-2的发酵产物中分离鉴定了10个化合物:preechinulin(1)、cyclo-(L-Trp-D-Val)(2)、(+)-neoechinulin A(3)、neoechinulin B(4)、crypotechinulin C(5)、cyclo-(L-Trp-L-Ala)(6)、variecolorin H(7)、2-(E-1-庚烯基)-3,6-二羟基-5-(3-甲基-2-丁烯基)苯甲醛(8)、2-(E,E-3,5-庚二烯基)-3,6-二羟基-5-(3-甲基-2-丁烯基)苯甲醛(9)和2-(E,E-1,3-庚二烯基)-3,6-二羟基-5-(3-甲基-2-丁烯基)苯甲醛(10)。化合物2、4和8分别对产气杆菌Enterobacter aerogenes、大肠杆菌Escherichia coli、枯草芽孢杆菌Ba-cillus subtilis具有弱的抗菌活性。结论浒苔共生真菌HT-2菌株能代谢产生具有抑菌活性的化合物。     

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。     

头孢美唑联合加替沙星对33株产超广谱β-内酰胺酶细菌的联合药敏研究

目的:评价头孢美唑与加替沙星对33株临床分离的产超广谱β-内酰胺酶(ESBL)细菌的联合抗茵效应.方法:采用棋盘法设计,微量肉汤稀释法测定.测定不同浓度组合的两种抗茵药物对33株ESBL茵(其中20株大肠埃希茵,13株肺炎克雷伯茵)的最低抑茵浓度,并计算FIC指数.结果:头孢美唑与加替沙星联合应用后对大肠埃希茵和肺炎克雷伯茵的浓度累积抑茵百分率曲线均比单独应用明显左移.FIC指数结果表明:头孢美唑与加替沙星联合应用后对大肠埃希茵60%为协同作用,40%为相加作用,没有无关作用,没有拮抗作用;对肺炎克雷伯茵53.85%为协同作用,38.46%为相加作用,7.69%无关作用,无拮抗作用.结论:对多种抗生素耐药的ESBL茵对加替沙星耐药率较高,对头孢美唑较稳定.两种抗茵药联合应用后MIC明显降低,抗茵作用明显加强.     

邵逸夫医院抗菌药物使用情况调查

目的:调查邵逸夫医院抗茵药物的使用情况,学习该院的抗菌药物监管机制,了解管理效果.方法:对该院2004年12月16日的门诊处方及2004年12月第二周的出院病历进行抽查分析,利用信息库调查了2004年全年西药和抗茵药物的使用金额及历年抗菌药物占药品的使用比例.结果:该院抗茵药物占全年西药总额的19.58%,门诊处方中抗菌药物的使用以口服为主,病区60份病例中以二代头孢和喹诺酮类药物使用量最大,细菌耐药性调查发现常见病原菌的耐药率较高.结论:临床医生应根据院内感染科提供的病原茵耐药率情况来筛选抗茵药,建立一整套抗茵药物合理使用的监管机制,能够控制并降低抗茵药物的使用率.     

1-乙基-6-氟-1,4-二氢-4-氧代-7-(4-芳酰硫代氨甲酰基-1-哌嗪基)-3-喹啉羧酸的合成及抗菌作用

1-乙基-6-氟-1,4-二氢-4-氧代-7-(1-哌嗪基)-3-喹啉羧酸(氟哌酸,norfloxacin),因有抗菌谱广、抗菌活性强等优点而引起人们广泛的兴趣,但尚有排泄快、生物利用度低等缺点。鉴于众多芳酰基硫脲衍生物有抗真菌、抗病毒和抗细菌等广谱生物活性,设想将芳     

我院2004-2006年住院患者抗菌药物应用分析

目的 评价医院住院患者抗茵药物的应用现状.方法 对2004-2006年住院患者抗茵药物的品种及用药频度等数据进行回顾性分析.结果 青霉素类,喹诺酮类和第3代头孢类品种数稳居前三,各大类抗茵药物中国家基本药物所占比率均较高,抗茵药物品种相对固定,变化不大.结论 医院各大类抗茵药物的应用基本合理,3年间消耗量在前10位的抗茵药物品种相对固定,可能导致细茵对某些使用量大的药物产生耐药性.     

白刺链霉菌15-4-2中的抗MRSA活性成分研究

目的研究白刺链霉菌(Streptomyces albospinus)15-4-2发酵液中的抗耐甲氧西林金葡菌(MRSA)活性成分。方法通过活性跟踪,采用柱层析等方法对白刺链霉菌15-4-2的次生代谢产物进行分离纯化。采用光谱分析对活性成分进行结构解析。结果分离鉴定了7个化合物,其结构分别为N-(2-羟基-1-(4-甲氧基苯基)乙基)乙酰胺(1)、2-(4-甲氧基苯基)-2-(丙胺基)乙醇(2)、cytoxazone(3)、对羟基苯甲酸(4)、(2S,3R)-3-羟基-2-甲基丁酸(5)、对甲基苯酚(6)和1,4-二甲氧基苯(7)。结论抗菌活性测试结果表明化合物1、3、4、5和6具有抗耐甲氧西林金黄色葡萄球菌(MRSA)活性。其中,1、3、4和5的抗耐甲氧西林金黄色葡萄球菌活性为首次报道。     

Studies on condensed-heterocyclic azolium cephalosporins. I. Synthesis and antibacterial activity of 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)- alkoxyiminoacetamido]-3-(imidazo[1,2-a]pyridinium-1-yl)methyl-3- cephem-4-carboxylates.

In our study of the structure-activity relationships of cephalosporins bearing quaternary ammonium groups at the 3 position, we postulated that delocalization of the azolium positive charge would lead to an expanded antibacterial spectrum and increased activity. Since quaternization of condensed-heterocyclic compounds such as imidazo[1,2-a]pyridine gives positive charge delocalization, 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-alkoxyiminoacetamido] cephalosporin derivatives (1-53) bearing various (imidazo[1,2-a]pyridinium-1-yl)methyl moieties at the 3 position were prepared and their antibacterial activity was determined. As expected, these cephalosporins exhibited potent activity against both Gram-positive and Gram-negative bacteria including Pseudomonas aeruginosa. These results imply that imidazo[1,2-a]pyridine is a quite useful substituent for improving antibacterial activity and spectrum. The structure-activity studies revealed that a favorable substituent on the imidazo[1,2-a]pyridine is the cyano radical at the 6 position of the ring, and ethoxyimino or 1-carboxy-1-methylethoxyimino groups are suitable for the alkoxyimino substituent. Among the cephalosporins tested, 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)- ethoxyiminoacetamido]-3-(6-cyanoimidazo[1,2-a]pyridinium -1-yl)methyl-3-cephem-4-carboxylate (45) and 7 beta-[2-(2-aminothiazol-4-yl)-2(Z)-(1- carboxy-1-methylethoxyiminoacetamido]-3-(6-cyanoimidazo[1,2- a] pyridinium-1-yl)methyl-3-cephem-4-carboxylate (49) showed good antibacterial activity.     

Recent progresses on AI-2 bacterial quorum sensing inhibitors

Quorum sensing (QS) is a communication procedure that predominates gene expression in response to cell density and fluctuations in the neighboring environment as a result of discerning molecules termed autoinducers (AIs). It has been embroiled that QS can govern bacterial behaviors such as the secretion of virulence factors, biofilm formation, bioluminescence production, conjugation, sporulation and swarming motility. Autoinducer 2 (AI-2), a QS signaling molecule brought up to be involved in interspecies communication, exists in both gram-negative and -positive bacteria. Therefore, novel approaches to interrupt AI-2 quorum sensing are being recognized as next generation antimicrobials. In the present review article, we summarized recent progresses on AI-2 bacterial quorum sensing inhibitors and discussed their potential as the antibacterial agents.     

Design and synthesis of 2-hydroxyl-4-methoxyl-3-(3-methylbut-2-en-1-yl)-6-(4-phenylbenzoylamino)benzoic acid derivatives as antibacterial agents based on cajaninstilbene acid scaffold hopping

The prevalence of multidrug resistance among clinically significant bacterial pathogens underlines a critical need for the development of new classes of antibacterial agents with novel structural scaffolds. Cajaninstilbene acid (CSA), which is isolated from pigeonpea leaves, has shown potent antibacterial activity. In this study, a series of 2-hydroxyl-4-methoxyl-3-(3-methylbut-2-en-1-yl)-6-(4-phenylbenzoylamino)benzoic acid derivatives derived from CSA were designed and synthesized, and their antibacterial activities were evaluated. Several synthesized compounds exhibit better antibacterial activity than CSA against Staphylococcus aureus, Staphylococcus epidermidis, and two strains of methicillin-resistant S. aureus. Meanwhile, the results of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide assays illustrate the good selectivity between bacteria and normal cells of the most active compounds 6u and 6v . Furthermore, well combinations with bacterial RNA polymerase of 6u arising from docking study imply the possible mechanism of antibacterial activity of these synthetic compounds.     

Synthesis and biological activities of some 1,3-benzoxazol-2(3H)-one derivatives as anti-quorum sensing agents

Antibiotics are commonly used to treat microbial infections. Due to misuse or large-scale use of antibiotics, many pathogens have gained resistance which makes antibiotic treatments ineffective. The discovery that many bacteria use quorum sensing (QS) to regulate their virulence factor and pathogenicity production makes the QS system an attractive target for antimicrobial therapy. A series of 1,3-benzoxazol-2(3H)-one derivatives were designed and synthesized as QS inhibitors (QSIs) and tested for their QS inhibitory activities. In vitro quorum sensing inhibitor screen (QSIS) assay indicated that the 1,3-benzoxazol-2(3H)-one (compound 1), 5-chloro-1,3-benzoxazol-2(3H)-one (compound 6), 6-methyl-1,3-benzoxazol-2(3H)-one (compound 11), and 5-methyl-1,3-benzoxazol-2(3H)-one (compound 16), inhibit QS system in quorum sensing selector (QSIS)1 strain. These 4 QSIs also significantly reduced elastase production, biofilm formation and swarming motility of Pseudomonas aeruginosa PA01 strain. These results suggest that compound 1, 6, 11 and 16 may provide a starting point for the design and development of new anti-pathogenic drugs that restrict virulence of P. aeruginosa and possibly other clinically important human pathogens. In addition, these QSI molecules could potentially be used in combination with conventional antibiotics to increase the efficiency of disease control and to extend the life span of established antimicrobials.     

5-氨基-6,8-二氟-1-(5-氟-2-吡啶基)-7-(3-甲基-1-哌嗪基)-1,4-二氢-4-氧代喹啉-3-羧酸及其类似物的合成及其抗菌作用

目的设计合成1-位为5-氟-2-吡啶基的吡酮酸衍生物,并对其抗菌活性进行初步评价.方法以2,3,4,5-四氟-6-硝基苯甲酰基乙酸乙酯和2,4,5-三氟-3-甲氧基苯甲酰基乙酸乙酯为原料,经多步反应合成8个5-氨基-6,8-二氟-1-(5-氟-2-吡啶基)-7-(3-甲基-1-哌嗪基)-1,4-二氢-4-氧代喹啉-3-羧酸及其类似物.结果共合成15个新化合物,经¹HNMR和MS确证其结构,其中8个(8-15)为目标物.结论8个目标物对金黄色葡萄球菌-16、大肠埃希氏菌-26和铜绿假单孢菌-17的体外活性均低于环丙沙星.     

A 4-(o-methoxyphenyl)-2-aminothiazole: an anti-quorum sensing compound

The 4-(o-methoxyphenyl)-2 aminothiazole was synthesized by reacting o-methoxyacetophenone, iodine, and thiourea; and characterized by spectral UV–Visible, Infra-Red (IR), H¹ nuclear magnetic resonance, C¹³NMR, gas chromatography-mass spectroscopy, and thermal analyses. From the thermo gravimetric-differential thermal analysis curve, various kinetic parameters like order of reaction (n), energy of activation (E), pre-exponential factor (Z), entropy of activation (ΔS), and free energy change (G) have been calculated using Coats–Redfern, MacCallum–Tanner, and Horowitz–Metzger methods. The compound was evaluated for antibacterial activity against Bacillus subtilis 2063 and Escherichia coli 2931, and its mechanism of action was studied by fluorescence microscopy and scanning electron microscopy. A novel functional application of MPAT, a quorum sensing mediated inhibition of biofilm was studied in Pseudomonas aeruginosa, which is hitherto un-attempted.     

7-(吡啶-N-氧-2-巯基)-1-(2-氟乙基)-6,8-二氟-1,4-二氢-4-氧喹啉-3-羧酸的合成及抗菌活性

目的;根据喹诺酮类抗菌药和抗菌防腐剂２－巯基吡啶－Ｎ－氧化物的抗菌作用原理设计,合成化合物７－（吡啶－Ｎ－氧－２－巯基）－１－（２－氟乙基）－６,８－二氟－１,４－二氢－４－氧喹啉－３－羧酸,对其抗菌活性进行了研究。方法;合成此化合物,并研究其体外抗菌活性。     

3-(4-哌嗪-1-苯基)-6-取代-s-三唑并［3,4-b］［1,3,4］噻二唑盐酸盐的合成及抗菌活性

为了研究水溶性稠杂环化合物的合成方法及抗菌活性，本研究采用3-(4-氯苯基)-6-取代-s-三唑并［3,4-b］［1,3,4］噻二唑(2a～n)在相转移催化剂TBAI作用下与哌嗪发生亲核取代，再与盐酸成盐制备了3-(4-哌嗪-1-苯基)-6-取代-s-三唑［3,4-b］［1,3,4］噻二唑盐酸盐(3a～n)。用试管二倍稀释法研究了新化合物的体外抗菌活性。结果表明，合成的28个新化合物极性碱性哌嗪基的引入可提高化合物的抗菌活性。该类稠杂环化合物的结构有待进一步优化。