Investigation of the antibacterial and antifungal activity of thiolated naphthoquinones

The WHO has stated that antibiotic resistance is escalating to perilously high levels globally and that traditional therapies of antimicrobial drugs are futile against infections caused by resistant microorganisms. Novel antimicrobial drugs are therefore required. We report in this study on the inhibitory activity of the 1,4-naphthoquinone-2,3-bis-sulfides and 1,4-naphthoquinone sulfides against two bacteria and a fungus to determine their antimicrobial properties. The 1,4-naphthoquinone sulfides have potent activity with a minimum inhibitory concentration (MIC) of 7.8 μg/mL against Staphylococcus aureus (Gram +ve), an MIC of 23.4 μg/mL against the fungus, Candida albicans, which was better than that of Amphotericin B (MIC = 31.3 μg/mL), and against Escherichia coli (Gram −ve) an MIC of 31.3 μg/mL was obtained. The 1,4-naphthoquinone had an MIC of 11.7 μg/mL against S. aureus and the 1,4-naphthohydroquinone also had the same activity against E. coli.

巴洛沙星的体外抗菌作用研究

目的评价巴洛沙星的体外抗菌作用。方法以琼脂稀释法测定巴洛沙星对临床分离菌的最低抑菌浓度，并与有关抗菌药进行比较；测定巴洛沙星的杀菌作用，观察巴洛沙星的抗菌活性影。结果巴洛沙星对革兰氏阳性菌及革兰氏阴性菌具广谱抗菌活性，尤其对葡萄球菌、肺炎球菌、肠球菌等革兰氏阳性菌活性优于诺氟沙星、氧氟沙星和环丙沙星。巴洛沙星有较强的杀菌作用，其MBC与MIC相一致，在体外具有较长的抗菌后效应。结论巴洛沙星是一种广谱抗菌药，抗菌作用强，临床应用前景好。     

Evaluation of metal concentration and antioxidant,antimicrobial, and anticancer potentials of two edible mushrooms Lactarius deliciosus and Macrolepiota procera

This study is designed for the determination of metal concentrations, antioxidant, antimicrobial, and anticancer potential of two edible mushrooms Lactarius deliciosus and Macrolepiota procera. Concentrations of nine metals are determined and all metals are present in the allowable concentrations in the tested mushrooms except Cd in M. procera. Antioxidant activity was evaluated by free radical scavenging and reducing power. M. procera extract had more potent free radical scavenging activity (IC₅₀ = 311.40 μg/mL) than L. deliciosus extract. Moreover, the tested extracts had effective reducing power. The total content of phenol in the extracts was examined using Folin–Ciocalteu reagent and obtained values expressed as pyrocatechol equivalents. Further, the antimicrobial potential was determined with a microdilution method on 15 microorganisms. Among the tested species, extract of L. deliciosus showed a better antimicrobial activity with minimum inhibitory concentration values ranging from 2.5 mg/mL to 20 mg/mL. Finally, the cytotoxic activity was tested using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide method on human epithelial carcinoma HeLa cells, human lung carcinoma A549 cells, and human colon carcinoma LS174 cells. Extract of both mushrooms expressed similar cytotoxic activity with IC₅₀ values ranging from 19.01 μg/mL to 80.27 μg/mL.     

复方联苯苄唑的体外抗真菌作用

摘目的研究联苯苄唑和曲安奈德联合应用时的体外抗菌活性。方法用微量肉汤稀释法，测定联苯苄唑等9种抗真菌药物对456株真菌的最低抑菌浓度，检测联苯苄唑与曲安奈德(10：1)联合作用时的最低抑菌浓度，计算联合药敏指数(FIC)。结果联苯苄唑对以红色毛癣菌为代表丝状真菌和白色念珠菌等均有较强的抗菌活性，其抗菌活性略强于益康唑、酮康唑、克霉唑和咪康唑。联苯苄唑与曲安奈德10：1配比时，体外抗菌作用呈无关作用。结论联苯苄唑具有较强的抗菌活性，曲安奈德对其活性无影响，建议将2者联合制成复方制剂。     

Evaluation of antimicrobial efficacy of flavonoids of withania somnifera L

In the present study antimicrobial activity of Withania somnifera L. Dunal (Solanaceae) has been evaluated against selected pathogens. Free and bound flavonoids of different parts (root, stem, leaf and fruit) of W. somnifera have been studied for their antimicrobial activity using disc diffusion assay against three Gram negative bacteria (Escherichia coli MTCC 46, Proteus mirabilis MTCC 3310 and Pseudomonas aeruginosa MTCC 1934), one Gram positive bacteria (Staphylococcus aureus MTCC 3160) and three fungi (Candida albicans MTCC 183, Aspergillus flavus MTCC 277 and Aspergillus niger MTCC 282). Minimum inhibitory concentration (MIC) of the extracts was evaluated through micro broth dilution method, while minimum bactericidal/fungicidal concentration was determined by sub culturing the relevant samples. C. albicans was found to be the most susceptible organism followed by S. aureus, P. mirabilis, E. coli and P. aeruginosa. Out of the tested organisms, A flavus and A. niger were observed to be resistant as none of the tested extracts showed activity against them. Total activity (TA) of extracts (ml/g) against each sensitive pathogens was also evaluated. Bound flavonoid extract of root showed best activity against C. albicans (IZ 30, MIC 0.039, MFC 0.039, respectively). However all the microorganisms were found to be sensitive against the extracts tested. Total activity of bound flavonoid extract of root was found to be same for E.coli, P. mirabilis, S. aureus and C. albicans (153.84 ml/g). Results of the present study reveal that extracts of W. somnifera showing great antimicrobial potential against test microorganisms may be exploited for future antimicrobial drugs.     

Direct anticancer activity of gonadotropin-releasing hormone-III

Abstract: In previous studies GnRH-III, a variant of the hypothalamic neurohormone GnRH, was isolated from the brain of the sea lamprey and structurally characterized. GnRH-III is a hypothalamic neurohormone in both female and male sea lampreys. In the present work biological activities of GnRH-III in mammalian systems were examined. In superfused rat pituitary cells, GnRH-III at 1 nM to 100 nM neither induced LH-secretion nor inhibited the LH-secretion elicited by native GnRH and elicited LH release only at 1 μM. At high dose (500 μg/day) in vim, GnRH-III behaved as a GnRH agonist, though, it was 1000-fold less active than ovurelin. The in vitro and in vivo results were in good agreement in showing that GnRH-III is only a weak agonist of the endocrine activity of GnRH. GnRH-III specifically bound to receptors on cancer cells and recognized not only the high-, but also the low-affinity binding sites. GnRH-III significantly suppressed growth of human cancer cells which have GnRH receptors. The inhibitory effect of GnRH-III on growth of cancer cells was specific and direct since the peptide did not have endocrine activity in the concentration range found to be effective in anticancer assays. GnRH-III inhibited equally the growth of ER-positive and -negative breast and TeR-positive and -negative prostate cells.     

Plants used to treat skin diseases in northern Maputaland,South Africa: antimicrobial activity and in vitro permeability studies

Context: Ethnobotanical claims of medicinal plants used in northern Maputaland are limited.

Objectives To establish scientific validity for a selection of the plants used in Maputaland to treat skin diseases.

Materials and methods: Aqueous and dichloromethane–methanol extracts were prepared from 37 plant species which were collected from four rural communities in Maputaland. Antimicrobial screening was performed on extracts against 12 dermatological relevant pathogens using the micro-titre plate dilution assay. Their combined effect was evaluated by determining the sum of the fractional inhibitory concentrations (ΣFICs). Chemical analysis was undertaken using reverse-phase high-performance liquid chromatography (RP-HPLC) and investigated in vitro across excised intact porcine skin using the ILC07 automated system.

Results: The organic extract of Garcinia livingstonei T. Anderson (Clusiaceae) was found to be the most antimicrobially active displaying an average broad-spectrum MIC value of 270?μg/mL. The combination of Sclerocarya birrea (A. Rich.) Hotsch. (Anacardaceae) with Syzygium cordatum Hochst. ex C. Krauss (Myrtaceae) displayed synergistic effects. The four antimicrobially active organic extracts were found to possess mainly anthraquinones, flavonoids, tannins and saponins. The organic extracts of Kigelia africana (Lam.) Benth. (Bignoniaceae) and S. cordatum were found to have more compounds capable of permeating intact skin after 10?min of exposure.

Conclusion: More than 80% of the organic extracts tested displayed a correlation between the antimicrobial efficacy and the reported traditional uses of the plants. Furthermore, the traditional use of topically applied plant preparations is validated as some compounds from the active plants are capable of permeating the skin in vitro.     

头孢硫脒最低抑菌浓度及其影响因素研究

目的评价头孢硫脒对近年来中国临床分离致病菌的体外最低抑菌浓度(MIC)及影响因素。方法以琼脂二倍稀释法对794株临床分离致病菌进行了MIC测定。比较细菌接种量、培养基pH、培养基血清蛋白含量改变后对头孢硫脒MIC值的影响。结果头孢硫脒对苯唑西林敏感金黄色葡萄球菌(MSSA)和表皮葡萄球菌(MSSE)的MIC₉₀值分别为0.50,0.12 mg·L^-1;对青霉素敏感肺炎链球菌(PSSP)MIC₉₀值为0.12 mg·L^-1,对青霉素不敏感肺炎链球菌(PNSSP)MIC₉₀值≤1 mg·L^-1;对化脓性链球菌MIC₉₀值为8μg·L^-1;对氨苄西林敏感粪肠球菌和屎肠球菌MIC₉₀值分别为1,16 mg·L^-1。头孢硫脒对氨苄西林敏感嗜血杆菌属和卡他莫拉菌MIC₉₀值≤4 mg·L^-1。头孢硫脒对革兰氏阳性厌氧菌也有一定抗菌作用。以上因素对头孢硫脒抗菌活性基本无影响。结论头孢硫脒对包括肠球菌在内的革兰氏阳性菌具有较强的抗菌作用。     

Investigation of a new horizon antifungal activity with enhancing the antimicrobial efficacy of ciprofloxacin and its binary mixture via their encapsulation in nanoassemblies: in vitro and in vivo evaluation

The main goal of this study was to prepare and evaluate nanosponges containing ciprofloxacin (CIP) or its binary mixture with N-acetyl carnosine (NAC). Nanosponges were prepared by ultrasound-assisted synthesis technique using hydroxypropyl βeta-cyclodextrin (HPβ-CD), as the polymer and diphenyl carbonate (DPC) as the crosslinker. Entrapment efficiency (EE%) of CIP or its binary mixture with NAC in nanosponges was deduced spectrophotometrically. Nanosponges were characterized using several methods. EE% of CIP or its binary mixture with NAC inside nanosponges ranged from 98.63 ± 3.1 to 100 ± 0.07%. Particle size of nanosponges ranged from 66.7 to 90.1 nm. Release of drugs from nanosponges was biphasic and the release pattern followed Korsmeyer–Peppas model. Ex vivo and in vivo studies results showed that the antibacterial effect was enhanced with encapsulation of drugs in the nanosponge system. Furthermore, a potent antifungal activity was obtained from all examined formulae against Candida albicans (10231). The study revealed that successful encapsulation of CIP or its binary mixture with NAC in nanosponge formulations has innovated a new promising therapeutic activity for both drugs.     

New thiazolyl-pyrazoline derivatives bearing nitrogen mustard as potential antimicrobial and antiprotozoal agents

A new series of N-substituted pyrazoline derivatives 6a–g , 7a–g , 8a–g , and 9a–g was synthetized by reaction of hydrazine derivatives and chalcone–thiazole hybrids bearing nitrogen mustard 5a–g . The chalcones 5a–g were obtained by Claisen–Schmidt condensation of thiazole-2-nitrogen mustard 3 and selected acetophenones 4a–g . These new compounds 6/7/8/9a–g were screened for their antifungal activity against Cryptococcus neoformans, with IC₅₀ values of 3.9–7.8 µg/ml for the N-3,5-dichlorophenyl pyrazolines 9e – g . Interestingly, those compounds show low cytotoxic effects toward erythrocytes (RBC). In addition, N-acetyl ( 6a,b ) and N-formyl pyrazolines ( 7a , 7b , 7c , and 7g ) showed inhibitory activity against methicillin-susceptible Staphylococcus aureus, methicillin-resistant S. aureus, and vancomycin-intermediate S. aureus, with the most important minimum inhibitory concentration values ranging from 31.25 to 125 µg/ml. Regarding the antiprotozoal activity, thiazolyl-pyrazolines 9g , 8f , and 7c display high activity against Plasmodium falciparum, Leishmania (V) panamensis, and Trypanosoma cruzi, with EC₅₀ values of 11.80, 6.46, and 4.98 μM, respectively, and with 7c being approximately 2.6-fold more potent than benznidazole with a selectivity index of 1.61 on U-937 human cells, showing promising potential as a novel antitrypanosomal agent.     

Formulation Optimization of Chitosan-Stabilized Silver Nanoparticles Using In Vitro Antimicrobial Assay

Antimicrobial resistance at the infected site is a serious medical issue that increases patient morbidity and mortality. Silver has antibacterial activity associated with some dose-dependent toxicity. Silver nanoparticles, due to larger surface area, have antibacterial properties, which make them useful in the treatment of infections. Chitosan-stabilized silver nanoparticles (CH-AgNP) were formulated and evaluated for minimal inhibitory concentration and minimal bactericidal concentration testing against Staphylococcus aureus ATCC 29213, S aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Escherichia coli ATCC 25922, and 20 methicillin-resistant S aureus isolates. Minimum biofilm eradication concentration study was used to evaluate the biofilm reduction, and in vitro antimicrobial checkerboard assays were performed. The effective optimum ratio of AgNP:chitosan solution was 1:4. Minimal inhibitory concentration and minimal bactericidal concentration ranges of CH-AgNP were 4 to 14 times lower compared to AgNP alone against methicillin-resistant S aureus isolates. Minimum biofilm eradication concentration values of CH-AgNP for ATCC PA-01, P aeruginosa isolate 1, and P aeruginosa isolate 2 were found to be >84.59 μg/mL, 42.29 μg/mL, and 21.15 μg/mL, respectively. Thus, CH-AgNP is a potential formulation for wound treatment and management of infected sites associated with antimicrobial resistance.     

司帕沙星衍生物(YH37)体外抗微生物活性研究

采用微量稀释法测定了5-氨基-1-环丙基-6，8-二氟-1，4-二氢-7-（3-甲基-1-哌嗪基）-4-氧代喹啉-6-羧酸（YH37）对临床分离的人型支原体（Mh）、解脲脲原体（Uu）以及细菌标准菌株的体外敏感性。结果显示，YH37对Mh的抑制活性较强，MIC90为0．25mg／L，是司帕沙星的1／8；对Uu的MIC90为1mg／L，是司帕沙星的1／4。YH37对Mh、Uu的喹诺酮耐药株有一定的抑制活性，其MIC分别为CPLX的1／4～1／16。YH37对被测细菌的抑制活性是左氧氟沙星的1／8～1／16，是司帕沙星的1／2。     

5个丹皮酚酯的合成和体外抗肿瘤活性研究

丹皮酚与相应的酰氯反应得到5个新的丹皮酚酯,其结构通过光谱法确证.它们的体外抗肿瘤活性通过MTT法和集落形成法进行了评价.初步的体外生物试验结果表明,5-硝基-2-呋喃甲酸的丹皮酚酯对人肿瘤细胞有一定抑制作用,其结果和临床上常用的抗肿瘤药5-Fu相近.     

20种抗菌药物对肺炎链球菌的体外抗菌活性研究

目的：评价莫西沙星等20种常用抗菌药物对临床分离的60株肺炎链球菌的体外抗菌活性。方法：采用微量肉汤稀释法测定20种抗菌药物对肺炎链球菌的最低抑菌浓度（MIC）。结果：60株肺炎链球菌中有青霉素敏感的肺炎链球菌（PSSP）42株（71．7％）,青霉素不敏感肺炎链球菌（PNSSP）18株（28．3％）;其中,青霉素耐药的肺炎链球菌（PRSP）有2株（3．3％）。对PSSP菌株,20种抗菌药物中敏感率较高的药物有头孢曲松、头孢噻肟、加替沙星、莫西沙星、左氧氟沙星、阿莫西林／克拉维酸,敏感率均为100％;耐药率较高的药物有红霉素、罗红霉素、克拉霉素、阿奇霉素,耐药率分别为83-3％,83-3％,74．7％,74．7％。对PNSSP菌株,敏感率较高的药物有阿莫西林／克拉维酸、莫西沙星、头孢噻肟、加替沙星、左氧氟沙星,敏感率分别为100％,100％,88．8％,94．4％,94．4％;耐药率较高的药物有红霉素、克拉霉素、阿奇霉素,耐药率均为66．7％。20种抗菌药物对60株肺炎链球菌的累积抑菌百分率曲线显示莫西沙星和阿莫西林／克拉维酸的抑菌能力最强。结论：肺炎链球菌对大环内酯类、复方新诺明、磷霉素等抗菌药物的耐药率较高,第三、四代氟喹诺酮类药物（左氧氟沙星、莫西沙星、加替沙星）和阿莫西林／克拉维酸及第三代头孢菌素中的头孢噻肟、头孢曲松等对肺炎链球菌（包括PNSSP）有很好的抗菌活性,提示其可作为高度耐药肺炎链球菌感染的首选药物。     

冈村凹顶藻的倍半萜类化学成分及抗菌活性研究

目的 分离鉴定冈村凹顶藻中的倍半萜类成分,供抗菌活性筛选。方法 综合利用各种柱层析方法分离纯化化合物并利用光谱学方法解析化合物结构;选择4株真菌为实验菌株,对6个倍半萜进行体外抗真菌活性测定;选择2株细菌为实验菌株,对所有倍半萜进行体外抗细菌活性测定。结果 分离得到17个倍半萜,分别鉴定为海兔阿普里醇 (1)、劳藻过氧素 (2)、海兔阿普里醛 (3)、 α-异溴花侧伯烯 (4)、α-异花侧伯烯醇 (5)、花侧伯烯醚 (6)、月桂烷-11-烯-10-醇 (7)、劳藻酚 (8)、劳藻酚乙酰化物 (9)、去溴劳藻酚 (10)、异劳藻酚 (11)、异劳藻酚乙酰化物 (12)、约翰斯顿醇 (13)、帕西菲醇 (14)、10-溴-α-花柏烯 (15)、10-溴-β-花柏烯 (16)、9-羟基-3-氯-4,10-二溴-α-花柏烯 (17),并对所获得的倍半萜进行抗菌活性筛选。结论 化合物5和7为首次从冈村凹顶藻中分离得到;应用1D和2D NMR首次对化合物6的1H和13C NMR数据进行了全归属;化合物5和13对光滑假丝酵母菌显示了明显的抑制作用,其MIC80值分别为1和4 μg/mL,与两性霉素B（2 μg/mL）和氟康唑（1 μg/mL）相当,而化合物2、8和9对新生隐球菌均具有一定的抑制作用;另外,化合物2、8~10、15和17对金黄色葡萄球菌均显示了不同程度的抑制作用,其中化合物8和9具有良好的杀菌活性,其MIC80值分别为2.3和10.5 μg/mL。     

Synthesis and antibacterial activity and antifungal activity of 2-R-4-R′-quinolines

2-R-4-R′-quinolines, where R is a thienyl-2,2,2′-bithienyl-5-yl, or 1,1′-biphenyl-4-yl group and R′ is an azidocarbonyl- or carboethoxyamino group, were found to have antimicrobial activity against the diphtheria bacillus and Staphylococcus P-209. Translated from Khimiko-Farmatsevticheskii Zhurnal, Vol. 43, No. 1, pp. 12–13, January, 2009.     

Synthesis, antimicrobial and antioxidant activity of some oxindoles

The present work describes the synthesis and spectral analysis of some new 3(Z)-{4-[4-(arylsulfonyl)piperazin-1-ylbenzylidene)-1,3-dihydro-2H-indol-2-one (5a-j). Ten of the synthesized compounds were screened in vitro against six species of microorganisms, Staphylococcus aureus, Streptococcus pyogenes, Escherichia coli, Pseudomonas aeruginosa, Asperigellus niger and Asperigellus clavatus. Most of the compounds exhibited significant antimicrobial activity. All of these compounds were also screened in vitro for the antioxidant activity using DPPH assay. Most of them have shown very significant antioxidant activity.     

2-甲基-3-取代苯基吡咯并吡嗪酮类化合物的合成及抗癌活性研究

目的 寻找具有抗癌活性的新吡咯并吡嗪酮类化合物。方法 以吡咯、对氨基苯乙酮为原料,经Friedel-Crafts酰化、醇解、亲核取代、环合及醇解反应制得母体化合物2-甲基-3-对氨基苯基吡咯并[1,2-a]吡嗪-1(2H)-酮,再通过酰基化/磺酰基化和烷基化反应引入酰基和烷基即制得系列吡咯并吡嗪酮类化合物。结果 合成了8个未见文献报道的吡咯并吡嗪酮类化合物,其结构经¹H-NMR、MS和IR谱确证。结论 8个目标化合物的体外抗乳腺癌细胞、肝癌细胞和肺癌细胞的活性试验结果显示,化合物4、5 具有明显的抗癌活性。     

茜草化学成分和抗癌活性研究

目的:研究茜草醋酸乙酯提取物的化学成分和测定其抗癌活性。方法:用硅胶柱色谱分离化学成分,利用各种光谱法确定其化学结构。采用MTT法测定体外抗癌活性,细胞株采用LH1210腹水癌细胞。结果:茜草醋酸乙酯提取物显示体外抗癌活性,从茜草醋酸乙酯提取物低极性部分中分离出6个单体化合物,其结构分别为:β-谷甾醇(Ⅰ)、二氢大叶茜草素(Ⅱ)、大叶茜草素(Ⅲ)、2-甲氧酰基-2,3-环氧基-3-异戊烯基-1,4-萘醌(Ⅳ)、大黄素甲醚(Ⅴ)、齐墩果酸(Ⅵ)。结论:化合物Ⅴ首次从该植物中分离得到,化合物Ⅳ显示了很强的抗癌活性。     

5-氟尿嘧啶衍生物的合成与抗肿瘤活性研究

目的寻找新型、高效的5-氟尿嘧啶衍生物类抗肿瘤化合物。方法设计、合成4个5-氟尿嘧啶衍生物,利用MTT方法测定这些化合物对4株肿瘤细胞的增殖抑制活性。结果 4个5-氟尿嘧啶衍生物均显示了较好的肿瘤细胞增殖抑制活性。结论 4个目标化合物对肿瘤细胞有较好的抑制活性,值得进一步研究。