5-氯水杨醛缩2,4-二羟基苯酰肼的抗菌抗氧化活性研究

目的考察5-氯水杨醛缩2,4-二羟基苯酰肼对金黄色葡萄球菌的抗菌活性及体外抗氧化活性。方法采用试管法和平板法测定其对金黄色葡萄球菌最小抑菌浓度(MIC)、最小杀菌浓度(MBC),绘制杀菌曲线,并通过扫描电镜研究其作用机制,采用DPPH法测定抗氧化活性。结果该化合物对金黄色葡萄球菌的MIC为2.5 mg/m L,MBC为5 mg/m L。杀菌曲线结果表明该化合物对金黄色葡萄球菌的杀菌作用表现出明显的浓度依赖性。扫描电镜结果表明该化合物的作用机制可能与破坏菌体细胞壁、改变其通透性有关。同时该化合物具有较强的清除自由基的能力。结论 5-氯水杨醛缩2,4-二羟基苯酰肼具有显著的抗金黄色葡萄球菌作用,同时具有较好的体外抗氧化活性。     

抗菌肽对种植体周围炎主要致病菌生长抑制作用的研究

目的研究抗菌肽KSL及其衍生物KSL—W对种植体周围炎主要致病菌的体外抑菌效果。方法应用二倍稀释法检测KSL和KSL—W对血链球菌、具梭核杆菌和牙龈卟啉单胞菌的最小抑菌浓度（MIC）和最小杀菌浓度（MBC）;MTT法检测KSL和KSL—W对成骨样细胞MG-63的细胞毒性。结果KSL和KSL—W对具梭核杆菌的MIC和MBC分别为0．0156mg／mL和0．0313mg／mL,对牙龈卟啉单胞菌的MIC和MBC分别为0．125mg／mL和0．5mg／mL,在0．5mg／mL的浓度范围内对血链球菌没有抑制作用;KSL和KSL-W在0．5mg／mL的浓度范围内没有细胞毒性。结论KSL和KSL—W没有细胞毒性,对具梭核杆菌和牙龈卟啉单胞菌具有抑制作用。     

紫穗槐种子提取物的抑菌活性研究

目的研究紫穗槐种子提取物的抑菌活性。方法将紫穗槐种子乙醇提取物分别通过石油醚、乙酸乙酯和正丁醇萃取,选择金黄色葡萄球菌和肺炎克雷伯杆菌为供试菌,采用试管二倍稀释法测定紫穗槐种子提取物的最小抑菌浓度（MIC）和最小杀菌浓度（MBC）,涂布平板法绘制杀菌曲线,电镜下观察药物对细菌超微结构的影响。结果紫穗槐种子提取物经乙酸乙酯萃取后对供试菌抑制作用较强,其中对金黄色葡萄球菌的MIC和MBC分别为2．5、5．0mg／mL;对肺炎克雷伯杆菌的MIC和MBC分别为5．0、10．0mg／mL;杀菌曲线结果表明,药物对供试菌的抑制作用存在浓度和时间依赖性;电镜结果说明,药物的作用可能与破坏菌体细胞壁、改变细胞膜通透性有关。结论紫穗槐种子提取物具有显著的抗菌活性。     

利褐喷丁衍生物体内外抗结核菌活性的研究

利福喷丁及其衍生物脱乙酰基利福喷丁对人型、牛型和草结核分枝杆菌的MIC10 0 分别为 2和 2、2和 2、0 .5和 0 .2 5mg/L。 10～ 4 0mg/kg剂量的利福喷丁组和脱乙酰基利福喷丁组小鼠半数动物存活时间(ST50 )均超过 2 8d ,2 .5和 5 .0mg/kg剂量的利福喷丁组小鼠ST50 分别为 18和 18d ,2 .5和 5 .0mg/kg剂量的脱乙酰基利福喷丁组小鼠ST50 分别为 16和 2 7d ,感染对照组小鼠ST50 为 13d。实验结果表明利福喷丁及其衍生物脱乙酰基利福喷丁有相似而良好的体内外抗结核分枝杆菌的活性。     

100种中草药对无乳链球菌和海豚链球菌体外抑杀研究

无乳链球菌(Streptococcus agalactiae)和海豚链球菌(Streptococcus iniae)给罗非鱼(Oreochromis sp.)养殖带来了严重的经济损失, 而抗生素等药物的使用会造成细菌的耐药性和环境污染, 因此, 研究了100种中草药对罗非鱼链球菌体外抑杀效果, 以筛选出替代抗生素的绿色中草药。其中16种中草药具有较好的抑菌作用, 但将其pH 值调至7.0±0.04后, 大部分中草药的抑菌效果会显著下降(P<0.01), 只有桑白皮(Morus alba)、藿香(Agastache rugosa)、豨莶草(Siegesbeckia orientalis)、槐角(Sophora japonica)的抑菌效果比较明显。将pH 值调至7.0±0.04后, 采用二倍梯度稀释法测定这4种中草药的最低抑菌浓度(Minimal Inhibitory Concentration, MIC)和最小杀菌浓度(Minimal Bactericidal Concentration, MBC), 结果显示, 桑白皮抑杀无乳链球菌的效果最好, MIC和MBC均为0.3906 mg·mL-1; 豨莶草抑杀无乳链球菌的效果次之, MIC为0.3906 mg·mL-1, MBC为0.7813 mg·mL-1; 藿香、豨莶草、槐角抑杀海豚链球菌的效果最好, MIC和MBC均为0.3906 mg·mL-1。     

7种消毒剂对鲟4种病原菌体外抑菌效果

为了筛选高效的消毒剂用于防治鲟细菌性疾病,采用二倍稀释法测定了7种消毒剂对鲟4种病原菌的最小抑菌浓度(MIC)和最小杀菌质量浓度(MBC)。结果显示,高铁酸钾对鲟4种病原菌抑菌效果最好,MIC为8 mg/L,MBC为8¹6 mg/L,戊二醛、甲醛、苯扎溴铵、过氧化氢及季铵盐络合碘5种消毒剂抑菌效果中等,聚维酮碘对鲟4种病原菌抑菌效果最差,聚维酮碘对鲟4种病原菌的MBC最大值为2048 mg/L。根据上述研究结果,选择抑菌效果好的消毒剂高铁酸钾进一步研究了鲟4种病原菌随时间和高铁酸钾浓度变化的生长趋势,显示消毒液浓度为5 mg/L、9 mg/L的消毒液在短时间能抑制病原菌生长繁殖,病原菌数量同样能在短时间内繁殖恢复到原来的水平,浓度为13 mg/L、17 mg/L的高铁酸钾消毒液能快速杀灭病原菌,病原菌在较长时间维持在较低水平,甚至病原菌全部被杀死。研究对于使用高铁酸钾防治鲟养殖实践中的疾病具有重要的指导意义。     

甘草提取物对四种牙周常见致病菌的抑菌作用

目的 体外评价甘草提取物对牙龈卟啉单胞菌、中间普氏菌、具核梭杆菌和伴放线放线杆菌四种牙周常见致病菌的抑制效果。方法 以牙龈卟啉单胞菌、中间普氏菌、具核梭杆菌和伴放线放线杆菌四种牙周常见致病菌作为供试菌,采用液体稀释法,考察甘草提取物对这四种细菌的最小抑菌浓度（MIC）和最小杀菌浓度（MBC）;并采用不同浓度的甘草提取物溶液,绘制甘草提取物对四种牙周致病菌的时间‒杀菌曲线。结果 甘草提取物对牙龈卟啉单胞菌、中间普氏菌、具核梭杆菌和伴放线放线杆菌的MIC值分别为1.50、1.50、0.75和1.50 mg/mL,MBC值分别为6、3、3和3 mg/mL。当甘草提取物达到对四种细菌的MBC值时,对于牙龈卟啉单胞菌、中间普氏菌、伴放线放线杆菌可在2 h后可达到杀菌效果,对于具核梭杆菌可在4 h后达到杀菌效果。结论 甘草提取物对以上四种牙周常见致病菌具有良好的抑菌及杀菌作用。     

二芳基喹啉类化合物抗结核效果及安全性

【背景】贝达喹啉作为治疗结核病的一种特效药,二芳基喹啉是以喹啉为骨架合成的一类化合物,但对于其在抗结核方面的研究鲜有报道。【目的】探究二芳基喹啉类化合物H2对结核分枝杆菌的抑菌效果和药物安全性,为药物研发奠定基础。【方法】采用比例法测定H2对不同结核分枝杆菌的最低抑菌浓度(minimum inhibitory concentration,MIC)和最小杀菌浓度(minimum bactericidal concentration,MBC),并选一线抗结核药物(异烟肼、利福平、乙胺丁醇)作为阳性对照,4周后观察结果;选昆明小鼠40只,分5个剂量组,灌胃给药,观察小鼠不同剂量下的存活状态及外观体征变化;根据LD50剂量,采用7d喂养实验,设3个剂量组(高、中、低)和空白对照组。实验结束,采取外周血并剖检,取各脏器称重,制作切片,观察病理改变。【结果】体外抑菌实验显示,H2对H37Rv的MIC与INH较相似,对耐药菌株仍有较好的抑菌效果;体内毒性试验显示,小鼠LD50为582.77 mg/kg。与空白组相比,高剂量组体质量在第5天差异极显著(P0.01),第6、7天差异显著(P0.05),红细胞计数、血小板和血小板比容差异显著(P0.05),肝脏系数差异极显著(P0.01)。镜下所见,剂量组肾脏组织有轻度炎症和水肿,肾小管上皮有轻度的水泡样变性,肝脏存在轻度的水肿和肝细胞的坏死。【结论】该化合物对不同结核分枝杆菌有较好的抑菌效果,有进一步开发、优化的意义。     

36种中药材体外抗菌活性筛选研究

该文研究36种常用中药材80%乙醇提取物在体外抗临床常见致病菌的抗菌活性。采用药敏纸片法测耐药菌的耐药谱,中药粗粉用80%乙醇浸泡提取,提取液减压浓缩得浸膏,通过琼脂打孔法测定提取物抑菌圈,再通过微量倍比稀释法测定最低抑菌浓度(MIC)和最低杀菌浓度(MBC)。结果表明:36种中药材醇提物中,有15种具有广谱抗菌活性,对实验中各标准菌表现出不同程度的抑制作用,对MRSA抗菌活性也较强。其中,岩陀、卷柏、首乌藤、苏木、乌药、夏枯草6种药材的抗菌活性比较突出,抑菌圈均大于11 mm,细菌对其表现为中高度敏感;它们对7株标准菌的MIC/MBC值除个别为12.5 mg·m L~(-1)以外,均小于1.563 mg·m L~(-1),对16株MRSA的MIC/MBC值均小于1.563 mg·m L~(-1),它们的萃取层活性均小于1 mg·m L~(-1)。所筛选出的15种抗菌活性较强的中药材,可为后续研究其活性单体化合物和作用机制,研发有效的抗多重耐药菌的中药制剂以及解决细菌耐药性问题提供一定的参考。     

蓝莓提取物对产超广谱β-内酰胺酶肺炎克雷伯菌的抑菌活性

【背景】随着细菌耐药性的增强,产超广谱β-内酰胺酶肺炎克雷伯菌的出现严重危害食品安全和人体健康。蓝莓中含有丰富的多酚和花青素,是天然抗菌材料的优选。【目的】分析蓝莓提取物对3株产超广谱β-内酰胺酶肺炎克雷伯菌的抑制活性及作用机制,并以牛乳为样品检测食品基质对蓝莓提取物抑菌活性的影响。【方法】利用甲醇制备巴尔德温和黑珍珠蓝莓提取物并检测提取物中总酚和花青素含量,利用纸片扩散法检测肺炎克雷伯菌的耐药性,利用最小抑菌浓度(minimum inhibitory concentration,MIC)、最小杀菌浓度(minimum bactericidal concentration,MBC)和生长曲线研究蓝莓提取物的抗菌活性,通过共聚焦激光扫描显微镜观察蓝莓提取物对细胞膜完整性的影响,并检测其在牛乳中的抑菌活性。【结果】巴尔德温和黑珍珠蓝莓提取物中的总酚含量分别为2.3 mg/g和3.5 mg/g,花青素含量分别为67.5 mg/100 g和92.5 mg/100 g。两种蓝莓提取物对肺炎克雷伯菌KP106、KP305和KP408的MIC均为25mg/mL,MBC均为50mg/mL。生长曲线表明...     

Synthesis and antimycobacterial evaluation of N-substituted 3-aminopyrazine-2,5-dicarbonitriles

A series of 14 new compounds related to pyrazinamide were synthesized, characterized with analytical data and screened for in vitro antimycobacterial activity against Mycobacterium tuberculosis, Mycobacterium kansasii and two types of Mycobacterium avium. The series comprised of N-substituted 3-aminopyrazine-2,5-dicarbonitriles derived from 3-chloropyrazine-2,5-dicarbonitrile by nucleophilic substitution of chlorine by various non-aromatic amines (alkylamines, cycloalkylamines and heterocyclic amines). Noteworthy antimycobacterial activity against M. tuberculosis was found among the alkylamino derivatives, for example, 3-(heptylamino)pyrazine-2,5-dicarbonitrile inhibited M. tuberculosis at MIC=51 μmol/L. 3-(Hexylamino)pyrazine-2,5-dicarbonitrile inhibited M. kansasii at MIC=218 μmol/L. Basic structure-activity relationships are discussed. A comparison between calculated and experimentally determined lipophilicity parameters within the series is included.     

Antimycobacterial activities of 5-alkyl (or halo)-3'-substituted pyrimidine nucleoside analogs

Several 5-alkyl (or halo)-3'-azido (amino or halo) analogs of pyrimidine nucleosides have been synthesized and evaluated against Mycobacterium bovis, Mycobacterium tuberculosis and Mycobacterium avium. Among these compounds, 3'-azido-5-ethyl-2',3'-dideoxyuridine (3) was found to have significant antimycobacterial activities against M. bovis (MIC(50)=1μg/mL), M. tuberculosis (MIC(50)=10μg/mL) and M. avium (MIC(50)=10μg/mL).     

Optimization of tuberculosis complex chemotherapy with the use of moxifloxacin]

It was shown in vitro that moxifloxacin by its activity against Mycobacterium tuberculosis (susceptible and resistant to the main antituberculosis agents) was highly superior to lomefloxacin (by 2 to 4 times by the MIC and by 4 times by the MBC). In murine lung tissue culture the highest effect was observed with the use of moxifloxacin in combination with isoniazid and pirazinamide. The efficacy of the regimens with the use of moxifloxacin was estimated in the treatment of 152 patients with pulmonary tuberculosis diagnosticated for the first time. The use of moxifloxacin was shown to be most advantageous in complex therapy of patients with extended and progressive tuberculosis due to polyresistant Mycobacterium tuberculosis strains or patients with concomitant nonspecific inflammatory diseases of the respiratory tracts due to a great variety of grampositive and gramnegative organisms, acid fact bacteria, atypical bacteria and a great variety of anaerobes. The tolerance of the treatment regimens with the use of moxifloxacin was mainly satisfactory.     

1,2,3]Triazolo[4,5-h]quinolones. A new class of potent antitubercular agents against multidrug resistant Mycobacterium tuberculosis strains

In this preliminary study we report the activity of 3-methyl-9-substituted-6-oxo-6,9-dihydro-3H-[1,2,3]-triazolo[4,5-h]quinolone-carboxylic acids and their esters as a new class of antiinfective agents against MDR Mycobacterium tuberculosis. In antitubercular screening against H37Rv and 11 clinically isolated strains of M. tuberculosis several derivatives (1o,3a,c,i,j,p) showed MIC(90) in the range 0.5-3.2 microg/mL. 3c showed no cytotoxicity and proved to be the most potent derivative exhibiting MIC(90)=0.5 microg/mL against all M. tuberculosis strains and infected human macrophages (J774-A1) tested.     

恩诺沙星对4种水产致病弧菌的抑杀菌效应

采用二倍稀释法测定恩诺沙星对溶藻弧菌、最小弧菌、哈维氏弧菌、创伤弧菌4种12株菌的最小抑菌浓度(MIC)和最小杀菌浓度(MBC),结果表明:恩诺沙星对12株弧菌的MIC为0.1?0.8 mg/L,MBC为0.4?3.2 mg/L。在此基础上,从每种菌中选取一株对恩诺沙星较为敏感的菌株,研究恩诺沙星不同药物浓度(1 MIC、2 MIC、4 MIC)对4种弧菌的杀菌动力学和抗菌后效应(PAE),结果显示:各浓度恩诺沙星对溶藻弧菌X040625-R菌株均有较强的杀菌作用,而对哈维氏弧菌M071202-H、创伤弧菌Q050723-C、最小弧菌H010911-Z等3菌株却表现出了低浓度抑菌、高浓度缓慢杀菌的作用。恩诺沙星的抗菌后效应PAE与药物浓度及细菌与药物的接触时间成正相关,恩诺沙星对溶藻弧菌X040625-R的PAE最长,对哈维氏弧菌M071202-H的PAE最短。     

Antimycobacterial activity of 9-sulfonylated/sulfenylated-6-mercaptopurine derivatives.

A series of 9-sulfonylated/sulfenylated-6-mercaptopurines has been prepared by reaction of 6-mercaptopurine with sulfonyl/sulfenyl halides. These compounds constitute a new class of potent antimycobacterial agents, possessing MIC values against Mycobacterium tuberculosis H37Rv in the range of 0.39-3.39 microg/mL, as well as appreciable activity against Mycobacterium avium. Furthermore, a compound of this small series exhibited good activity (MIC under 1 microg/mL) against several drug resistant strains of M. tuberculosis.     

Synthesis of isonicotinic acid N'-arylidene-N-[2-oxo-2-(4-aryl-piperazin-1-yl)-ethyl]-hydrazides as antituberculosis agents

A new series of antituberculosis agents 6-9 was designed, synthesized and evaluated for antituberculosis activity against Mycobacterium tuberculosis H37Rv and clinical isolates in an agar dilution method. Compound 9h showed comparable in vitro activity (MIC) to isoniazid against M. tuberculosis H37Rv and clinical isolates (sensitive strains) and superior activity against resistant strains of M. tuberculosis.     

Growth inhibitory properties of lactose fatty acid esters

Sugar esters are biodegradable, nonionic surfactants which have microbial inhibitory properties. The influence of the fatty acid chain length on the microbial inhibitory properties of lactose esters was investigated in this study. Specifically, lactose monooctanoate (LMO), lactose monodecanoate (LMD), lactose monolaurate (LML) and lactose monomyristate (LMM) were synthesized and dissolved in both dimethyl sulfoxide (DMSO) and ethanol. Minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) were determined in growth media. LML was the most effective ester, exhibiting MIC values of <0.05 to <5 mg/ml for each Gram-positive bacteria tested (Bacillus cereus, Mycobacterium KMS, Streptococcus suis, Listeria monocytogenes, Enterococcus faecalis, and Streptococcus mutans) and MBC values of <3 to <5 mg/ml for B. cereus, M. KMS, S. suis, and L. monocytogenes. LMD showed MIC and MBC values of <1 to <5 mg/ml for B. cereus, M. KMS, S. suis, L. monocytogenes, and E. faecalis, with greater inhibition when dissolved in ethanol. LMM showed MIC and MBC values of <1 to <5 mg/ml for B. cereus, M. KMS, and S. suis. LMO was the least effective showing a MBC value of <5 mg/ml for only B. cereus, though MIC values for S. suis and L. monocytogenes were observed when dissolved in DMSO. B. cereus and S. suis were the most susceptible to the lactose esters tested, while S. mutans and E. faecalis were the most resilient and no esters were effective on Escherichia coli O157:H7. This research showed that lactose esters esterified with decanoic and lauric acids exhibited greater microbial inhibitory properties than lactose esters of octanoate and myristate against Gram-positive bacteria.     

Antimycobacterial activities of novel 2-(sub)-3-fluoro/nitro-5,12-dihydro-5-oxobenzothiazolo[3,2-a]quinoline-6-carboxylic acid

Various 2-(sub)-3-fluoro/nitro-5,12-dihydro-5-oxobenzothiazolo[3,2-a]quinoline-6-carboxylic acid derivatives were synthesized from 2-aminothiophenol by a five-step reaction, evaluated for in-vitro and in-vivo antimycobacterial activities against Mycobacterium tuberculosis H37Rv (MTB), multi-drug resistant Mycobacterium tuberculosis (MDR-TB), and Mycobacterium smegmatis (MC2), and also tested for the ability to inhibit the supercoiling activity of DNA gyrase from M. smegmatis. Among the thirty-four synthesized compounds, 2-(3-(diethylcarbamoyl)piperidin-1-yl)-)-3-fluoro-5,12-dihydro-5-oxobenzothiazolo[3,2-a]quinoline-6-carboxylic acid (7l) was found to be the most active compound in vitro with MIC of 0.18 and 0.08 microM against MTB and MTR-TB, respectively. Compound 7l was found to be 2 and 570 times more potent than isoniazid against MTB and MDR-TB, respectively. In the in-vivo animal model 7l decreased the bacterial load in lung and spleen tissues with 2.78 and 3.12-log10 protections, respectively, at the dose of 50 mg/kg body weight.