dl-7-(4,4-二甲基-3-氨甲基-吡咯烷-1-基)-喹诺酮类化合物的合成与抗菌作用

目的寻找新的高效抗革兰氏阳性菌的喹诺酮类药物。方法设计合成了dl-7-(4,4-二甲基-3-氨甲基-吡咯烷-1-基)-1-环丙基-6-氟-8-甲氧基-1,4-二氢-4-氧代喹啉-3-羧酸及其类似物，测定其体外活性。结果共合成10个目标化合物，经¹H NMR，MS确证其结构。目标化合物具有良好的抗革兰氏阳性菌的活性，尤其是化合物22不仅对4株革兰氏阳性耐药菌(两株MRSA，两株MRSE)的活性表现突出，MIC值为0.015～0.5 mg·L^-1，其活性是加替沙星(MIC值为0.125～16 mg·L^-1)的4～128倍，而且，对铜绿假单孢菌03-5的MIC值为0.008 mg·L^-1，其活性是加替沙星(MIC值为0.03 mg·L^-1)的4倍。结论化合物22值得进一步深入评价。     

7-[3-氨甲基-4-(脲亚氨基)吡咯烷-1-基]喹诺酮衍生物的合成与抗菌作用研究

目的 寻找新的喹诺酮类抗菌药.方法 设计合成7-位具有较强亲水性取代基的7个氟喹诺酮衍生物,测定其体外抗菌活性.结果 化合物10对金葡菌(包括MRSA)和表葡菌(包括MRSE)的活性(MIC:0.06～4μg/mL)与左氧氟沙星和吉米沙星基本相当.化合物11对肺炎链球菌08-2的活性(MIC:0.25μg/mL)分别是左氧氟沙星和吉米沙星的128倍和32倍,化合物12对肺炎克雷伯菌09-22和09-23的活性(MIC:1μg/mL)分别是左氧氟沙星和吉米沙星的16倍和4倍,但目标物对革兰阴性菌的活性普遍弱于对照药.结论 7-位取代基的水溶性并非决定喹诺酮抗菌活性的主要因素.     

7-(7-氨甲基-5-氮杂螺［2,4］庚烷-5-基)-1-环丙基-6-氟-8-甲氧基-1,4-二氢-4-氧代喹啉-3-羧酸及其类似物的合成与抗菌作用7-(7-氨甲基-5-氮杂螺［2,4］庚烷-5-基)-1-环丙基-6-氟-8-甲氧基-1,4-二氢-4-氧代喹啉-3-羧酸及其类似物的合成与抗菌作用

目的寻找新的广谱、高效、低毒喹诺酮类抗菌药物。方法设计合成7-(7-氨甲基-5-氮杂螺［2,4］庚烷-5-基)-1-环丙基-6-氟-8-甲氧基-1,4-二氢-4-氧代喹啉-3-羧酸及其类似物,测定其体内外活性。结果共合成了20个新化合物,经¹HNMR,MS和HRMS确证其结构。其中5个目标化合物(22～26)有广谱活性,尤其对革兰氏阳性菌具有很强的活性。其中化合物24对所试的13株革兰氏阳性菌的MIC值均0.03 mg·L^-1,其活性优于对照药克林沙星和加替沙星,对所试的6株革兰氏阴性菌,其活性相当于或低于对照药。结论化合物(22～26)值得进一步评价。     

新一代抗菌药物Dalbavancin的研究进展

目的 综述新一代抗菌药物Dalbavancin的最新研究进展。 方法 通过检索Google Scholar以及Science Direct查阅大量近10年的相关文献,对Dalbavancin抗菌机制、抗菌活性、药动学、药效学以及安全性多角度综述分析。结果 Dalbavancin是一种糖肽类浓度依赖性抗菌药物,其体内外抗耐甲氧西林葡萄球菌(MIC50=0.06 mg·L^-1)的活性明显优于万古霉素(MIC50=1 mg·L^-1)、替考拉宁(MIC50=0.5 mg·L-1);其临床药动学表明具有每周给药1次的潜力,体内有效治疗浓度为20 mg·L^-1。结论 Dalbavancin是一种菌体耐药性突变率低,不良反应温和,药物毒性较小处于临床Ⅲ期研究的最具应用价值的新一代抗菌药物。     

7-{4-［2-［2-取代-4-((5S)-5-乙酰胺甲基-2-氧代-噁唑烷-3-基)苯基］乙基］哌嗪-1-基}-氟喹诺酮类化合物的合成与抗菌活性

目的寻找新型的噁唑烷酮-氟喹诺酮类抗菌药物。方法设计合成了7-{4-［2-［2-取代-4-((5S)-5-乙酰胺甲基-2-氧代-噁唑烷-3-基)苯基］乙基］哌嗪-1-基}-氟喹诺酮类化合物，测定其体外抗菌活性。结果共合成20个目标化合物，经^{1H NMR和MS确证结构。目标化合物具有较好的体外抗菌活性，尤其是化合物22，对屎肠球菌的抑制活性分别是吗啉噁酮和诺氟沙星的16倍和64倍，对金葡菌的抑制活性为吗啉噁酮的4倍。结论某些带有氟喹诺酮结构片段的噁唑烷酮类化合物抗菌活性加强。}     

含2-甲基-5-硝基咪唑的吡酮酸类衍生物的合成及其抗菌活性含2-甲基-5-硝基咪唑的吡酮酸类衍生物的合成及其抗菌活性

目的 研究含N-乙基-2-甲基-5-硝基咪唑的诺氟沙星、环丙沙星和依诺沙星衍生物的合成及其抗菌活性。方法 用含2-甲基-5-硝基咪唑的诺氟沙星、环丙沙星和依诺沙星等为原料,通过亲核取代、酯化合成目的物;测定目的物的抗菌活性。结果 设计、合成了9个新化合物(IIa～c,IIIa～f),其结构经MS,¹HNMR和元素分析确证。化合物IIa～c的体内抗菌活性较明显。结论 化合物IIa～c显示了一定的体内抗菌活性,值得进一步研究。     

HPLC-ELSD法测定贝母中异甾类生物碱及糖苷类成分的含量

目的建立同时测定贝母中5种异甾类生物碱——peimissine, imperialine, sinpeinine A, imperialine-3β-glucoside和yibeinoside A含量的HPLC分析方法。方法C₁₈柱;流动相:乙腈-水(含0.1%二乙胺);梯度洗脱,流速1.0 mL·min^-1;检测器:Alltech 500蒸发光散射检测器(ELSD)。结果线性范围为peimissine 13.1～288.2 mg·L^-1(r²=0.997 5), imperialine-3β-glucoside 7.7～169.4 mg·L^-1 (r²=0.999 3), yibeinoside A 7.3～160.6 mg·L^-1 (r²=0.999 7), imperialine 16.5～363.0 mg·L^-1 (r²=0.999 2), sinpeinine A 8.7～191.4 mg·L^-1 (r²=0.994 2)。 5个化合物的精密度和重现性RSD均<5%。结论本方法简便、有效、可行,可用于贝母中5种异甾类生物碱的含量测定。     

克林沙星在大鼠体内的药代动力学和生物利用度

目的　研究克林沙星在大鼠体内的药动学和生物利用度。方法　HPLC法测定大鼠ig和iv克林沙星后的血药浓度,计算药动学参数和生物利用度。色谱柱为C₁₈柱(5μm),流动相为乙腈-0.05mol·L^-1柠檬酸三乙胺液(pH2.5)(20∶80),流速为1.0mL·min^-1,检测波长300nm。结果　克林沙星0.1-20μg·mL^-1呈良好线性关系,在大鼠体内的药动学过程符合一室模型,大鼠ig50和100mg·kg^-1后,C_max和AUC均与剂量呈正比,T_1/2与剂量无关;绝对生物利用度(F)为42%。结论　克林沙星50-100mg·kg^-1的吸收和消除呈一级动力学特征,在大鼠体内的生物利用度低。     

脑5-HT1A/1B、α2受体及腺苷酸环化酶参与了胍丁胺的抗抑郁作用

为了在单胺受体及受体后腺苷酸环化酶(adenylate cyclase,AC)水平探讨胍丁胺(agmatine,AGM)抗抑郁作用的精细机制,采用小鼠悬尾实验和强迫游泳实验观察AGM抗抑郁行为改变。采用放射免疫方法测定大鼠前额皮层突触膜蛋白AC活性。结果表明,AGM(5～40 mg·kg^-1,ig)在小鼠悬尾实验和强迫游泳实验模型上均有显著抗抑郁活性。同时伍用β受体/5-HT_1A/1B受体阻断剂吲哚洛尔(pindolol, PIN, 20 mg·kg^-1, ip)、 α₂肾上腺素受体拮抗剂育亨宾(yohimbine, YOH, 5～10 mg·kg^-1, ip)或咪唑克生(idazoxan, IDA, 4 mg·kg^-1, ip)对AGM(40 mg·kg^-1, ig)的抗抑郁活性具有显著拮抗效应; 而β受体阻断剂普萘洛尔(propranolol, PRO, 5～20 mg·kg^-1, ip)或5-HT₃受体拮抗剂曲匹西隆(tropisetron, TRO, 5～40 mg·kg^-1, ip)对AGM(40 mg·kg^-1, ig)的抗抑郁活性无显著影响。AGM(0.1～6.4 μmol·L^-1)与大鼠前额皮层提取的突触膜共孵可剂量依赖地激活AC活性, 而PIN(1 μmol·L^-1)或YOH(0.25～1 μmol·L^-1)均显著拮抗AGM(6.4 μmol·L^-1)对AC的激活作用; 慢性给予大鼠AGM(10 mg·kg^-1, ig, bid)或氟西汀(fluoxetine, FLU, 10 mg·kg^-1, ig, bid) 2 w也显著增强大鼠前额皮层基础及Gpp(NH)p 预激活的AC活性。本研究表明, 调节脑内5-HT_1A/1B和α₂等受体功能, 并激活前额皮层AC可能是AGM抗抑郁活性的重要机制之一。     

水和非水毛细管电泳-电导检测法分离测定水杨酸类药物

目的建立水和非水毛细管电泳-电导法分离水杨酸类药物。方法用未涂层石英毛细管柱(55 cm×50 μm),以10 mmol·L^-1 Tris-30 mmol·L^-1 H₃BO₃(pH 8.0)为运行缓冲液,分离电压为24 kV,进样时间10 s,电导检测法。结果在非水实验条件下,水杨酸(SA)、乙酰水杨酸(ASA)和磺基水杨酸(SSA)得到很好的分离。SA,ASA和SSA的线性范围分别为0.05～100 mg·L^-1,5.0～250 mg·L^-1,0.08～100 mg·L^-1,r均大于0.995。结论应用于阿斯匹林制剂中水杨酸和乙酰水杨酸含量的测定,结果令人满意。与水介质相比,乙醇介质具有更高的灵敏度和分离效率。     

Synthesis and antimicrobial activity of some bisoctahydroxanthene-1,8-dione derivatives

The bisoctahydroxanthen-1,8-dione derivatives were synthesized effectively via p-dodecylbenzene sulfonic acid the catalysed cyclocondensation of cyclic 1,3-dicarbonyl compounds with 1,3- or 1,4-benzene dicarboxaldehydes in water. The products were obtained with yield ranged from 75 to 95%. The structures of compounds were characterized by FT-IR, ¹H-NMR and elemental analysis. The antimicrobial properties of compounds against pathogens were investigated by the disc-diffusion method. These compounds were evaluated for potential antimicrobial activity against Gram-positive (Staphylococcus aureus, Bacillus cereus, S. epidermidis and Nocardia canis), Gram-negative bacteria (Escherichia coli, Proteus vulgaris and Pseudomonas aeroginosa), yeasts (Candida albicans and Rhodotorula rubra) and mold (Aspergillus niger). The growth of S. aureus, B. cereus, S. epidermidis, E. coli, C. albicans, R. rubra and A. niger were inhibited by 3f and 3g compounds. All compounds were resistant against Gram-negative bacteria (Proteus vulgaris and Pseudomonas aerginosa) and results were upon comparison with reference discs.     

Synthesis and antibacterial activity of N-[5-chlorobenzylthio-1,3,4-thiadiazol-2-yl] piperazinyl quinolone derivatives

A series ofN-[5-(chlorobenzylthio)-1,3,4-thiadiazol-2-yl] piperazinyl quinolone derivatives (4a-1) have been synthesized by reaction of piperazinyl quinolones with 5-chloro-2-(chloroben-zylthio)-1,3,4-thiadiazoles. Their structures were confirmed by elemental analysis, IR and NMR spectra. The antibacterial activities of4a-1 against a variety of Gram-positive and Gram-negative bacteria were determined. Several compounds showed a good antibacterial activity against Gram-positive bacteria among which, compound 4e with a 2-chlorobenzylthio moiety in ciprofloxacin derivative, exhibited high activities againstStaphylococcus aureus andStaphylococcus epidermidis (MIC=0.06 μg/mL). The structure-activity relationship (SAR) study revealed that the position of chlorine atom on benzyl moiety would dramatically affect the antibacterial activities of the synthesized compounds.     

Exploration of (3-benzyl-5-hydroxyphenyl)carbamates as new antibacterial agents against Gram-positive bacteria

A series of (3-benzyl-5-hydroxyphenyl)carbamates were evaluated as new antibacterial agents. Several compounds showed potent inhibitory activity against sensitive and drug-resistant Gram-positive bacteria. The compounds are ineffective against all tested Gram-negative bacteria. The structure of the ester group exerted a profound effect on antibacterial activity. 4,4-Dimethylcyclohexanyl carbamate 6h exhibited the most potent inhibitory activity against the standard and clinically isolated Staphylococcus aureus, Staphylococcus epidermidis, and Enterococcus faecalis (minimum inhibitory concentration = 4–8 µg/ml) strains. The preliminary experimental evidence indicated that these carbamates target the bacterial cell wall and share a similar mechanism of action with vancomycin.     

国产盐酸洛美沙星体内外抗菌作用实验研究

盐酸洛美沙星对革兰阴性菌具有强的抗菌活性，其ＭＩＣ５０多数为０．２５ｍｇ·Ｌ－１；对金葡球菌ＭＩＣ５０为０．５ｍｇ·Ｌ－１；对绿脓假单胞菌ＭＩＣ５０为１ｍｇ·Ｌ－１。盐酸洛美沙星体外抗菌活性与诺氟沙星、氧氟沙星相近而略逊于环丙沙星。盐酸洛美沙星对金葡球菌、大肠杆菌和绿脓假单胞菌感染小鼠ｉｖ的ＥＤ５０分别是４．４７、１．６２和１７．１３ｍｇ·ｋｇ－１，体内抗菌作用较环丙沙星弱但强于诺氟沙星和／或氧氟沙星。     

2014-2015年中山市博爱医院儿科重症监护病房感染性病原菌的分布及耐药性分析

目的 分析2014-2015年中山市博爱医院儿科重症监护病房感染性疾病病原菌的分布及耐药性.方法 选取2014年3月-2015年11月中山市博爱医院儿科重症监护病房感染性疾病患儿标本906份,分析菌株标本来源、病原菌分布及主要耐药菌对常用抗菌药物的耐药性.结果 菌株标本共906份,主要来自痰液,构成比为52.76%.其中革兰阴性菌342例(37.75%),主要为大肠埃希菌、肺炎克雷伯菌、鲍曼不动杆菌、铜绿假单胞菌;革兰阳性菌535例(59.05%),主要为人葡萄球菌、金黄色葡萄球菌、表皮葡萄球菌、溶血葡萄球菌;真菌29例(3.20%),其中白色念珠菌24例.革兰阴性菌中,大肠埃希菌对氨苄西林、头孢唑啉呈高耐药性,肺炎克雷伯菌对氨苄西林、头孢唑啉耐药性明显较高,但对复方新诺明、环丙沙星、亚胺培南、左旋氧氟沙星均无耐药性,鲍曼不动杆菌对头孢唑啉、呋喃妥因耐药率较其他药物更高,铜绿假单胞菌对氨苄西林、头孢唑啉、呋喃妥因、复方新诺明呈高耐药性;革兰阳性菌中,人葡萄球菌对红霉素、青霉素G耐药性较高,金黄色葡萄球菌对青霉素G的耐药性明显高于其他药物,表皮葡萄球菌则对青霉素G、苯唑西林、红霉素有高度耐药性,溶血葡萄球菌对青霉素G耐药率高达100%.结论 儿科重症监护病房感染性疾病病原菌较为广泛,临床上应根据致病菌株及耐药情况选择针对性抗菌药物,避免抗生素的滥用.     

O,O′-二烷基-O″-(取代苯乙腈肟)磷酸酯、硫代磷酸酯的合成及对氯硝柳胺的灭螺增效作用

合成了20个O,O′-二烷基-O″-(取代苯乙腈肟)磷酸酯、硫代磷酸酯,并分别与杀螺剂氯硝柳胺组成复方,进行室内杀螺试验。初步结果表明,化合物V_4,7,12,18有明显杀螺增效作用,其中V12可使氯硝柳胺的杀螺效果提高3.81倍。同时发现化合物V_2,7,10,13单独使用时,也有良好的杀螺作用。     

Synthesis and antibacterial activity of 4-benzoyl-1-(4-carboxy-phenyl)-5-phenyl-1H-pyrazole-3-carboxylic acid and derivatives

A new 1H-pyrazole-3-carboxylic acid 2, along with hydrazono-pyridazinone 3, a by-product, and its derivatives 4–7 were synthesized and the structures confirmed by infrared (IR) and ¹H and ¹³C nuclear magnetic resonance (NMR) data. These new compounds were evaluated for their antibacterial activities against Gram-positive and Gram-negative bacteria using the tube dilution method. The minimal inhibitory concentrations (MICs) experiments revealed that most compounds exerted inhibitor effects against Klebsiella pneumonia, Escherichia coli, Bacillus subtilus, and Xanthomonas compestris test microorganisms. Moreover, the results showed that the pyrazolo[3,4-d]pyridazine compounds were the best compounds of the series, exhibiting antibacterial activity against both Gram-positive and Gram-negative bacteria.     

Antimicrobial and antioxidant activities of crude extracts of two Nigerian chewing sticks

In vitro determinations of the antimicrobial and antioxidant activities of ethanol and aqueous extracts of Disthemonanthus benthamianus Baill. (Caesalpiniaceae) and Zanthoxylum zanthoxyloides Lam. (Rutaceae), which are used as chewing sticks in Nigeria, were investigated. The extracts were screened against eight strains of Escherichia coli, Enterococcus faecalis, Staphylococcus aureus, one methicillin-resistant strain of Staphylococcus epidermidis, twelve strains of Pseudomonas aeruginosa, five strains of Candida albicans and four strains of Bacillus cereus. The in vitro antimicrobial assay was performed by using a Mast Multipoint Inoculator based on the principles of an agar dilution technique. The aqueous extracts had no inhibitory effects on any of the tested microorganisms. The ethanol D. benthamianus extract inhibited P. aeruginosa, E. faecalis, and B. cereus with MIC ≤ 2.64?mg mL^?1 and S. aureus and S. epidermidis with MIC ≤ 0.44?mg mL^?1. Z. zanthoxyloides ethanol extract was less effective but noteworthy was the MIC ≤ 2.52?mg mL^?1 against C. albicans and 0.28?mg mL^?1 against some S. aureus strains. D. benthamianus ethanol extract had the best antioxidant activity and Z. zanthoxyloides ethanol extract second best. IC₅₀ for DPPH free radical scavenging of these extracts were 87.76 and 128.28?μg mL^?1/mL, respectively; ascorbic acid equivalents were 2.4 and 9.5?mg mg^?1 and total antioxidant capacities using the FRAP assay were 4068.06?mM Fe⁺⁺ mg^?1 and 624.86?mM Fe⁺⁺ mg^?1, respectively. The ethanol extracts of D. benthamianus and Z. zanthoxyloides showed significant antimicrobial and antioxidant activities which could be beneficial in oral hygiene.     

2015-2016年襄阳市中医医院慢性阻塞性肺疾病急性加重期患者呼吸道病原菌分布及耐药性分析

目的 分析襄阳市中医医院慢性阻塞性肺疾病急性加重期患者呼吸道病原菌分布及耐药情况,为临床合理使用抗菌药物提供依据.方法 对2015—2016年襄阳市中医医院慢性阻塞性肺疾病急性加重期患者呼吸道病原菌的分布及耐药性进行回顾性分析.结果 共分离出病原菌376株,其中革兰阳性菌146株,占38.83%;革兰阴性菌209株,占55.59%;真菌21株,占5.58%.革兰阳性菌耐药率位于首位的为金黄色葡萄球菌,其次为表皮葡萄球菌、溶血葡萄球菌,对这3种细菌耐药率较低的有万古霉素、替考拉宁.革兰阴性菌中耐药率位于首位的是铜绿假单胞菌,其次为大肠埃希菌,对细菌耐药率较低的抗生素为亚胺培南、美罗培南.结论 慢性阻塞性肺疾病急性加重期患者的主要致病菌为革兰阴性菌,且耐药率较高,临床上应结合地区常见致病菌分布及耐药流行趋势,正确选择敏感抗菌药物.     

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.