Synthesis and evaluation of demethoxyviridin derivatives as potential antimicrobials

The in vitro antibacterial and antifungal activities of demethoxyviridin and some synthetic analogues were evaluated by the agar diffusion method. The minimum inhibitory concentrations (MIC) of the active compounds were also determined by the agar dilution method. Demethoxyviridin (1) showed moderate antibacterial activity against most of the strains tested. 1alpha-Hydroxydemethoxyviridin (3) showed antibacterial activity and the most potent in vitro antifungal activity with MIC of 20 microg/ml (0.062 mM) against Aspergillus niger, A. fumigatus, A. flavus, A. parasiticus, Fusarium solani, F. graminarum, Geotrichum candidum whereas 5'-methylfuro-(4',3',2'-4,5,6)androst-5-ene-3,17-dione (7) exhibited very weak antifungal activity against Candida albicans only.     

Antibacterial activity, structure and CMC relationships of alkanediyl alpha,omega-bis(dimethylammonium bromide) surfactants

Some alpha,omega-alkanediyl bis-dimethylammonium bromide compounds (gemini surfactants) referred as "m-s-m" have been synthesized, purified and characterized by usual spectroscopic methods. These compounds have been screened for antibacterial activity against Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus. Their activity was compared. The compounds tested showed excellent in vitro antibacterial activity against Staphylococcus aureus ranging from 1.5 to 20 microg/ml and had variable activity against E. coli with minimum minimum inhibitory concentration (MIC) of 50 microg/ml. These compounds are less active against P. aeruginosa. On the other hand, contrary to the antibacterial activity of these products against S. aureus, a relation between the MIC and the critical micellar concentration (CMC) was found and relationship between chain's Length and antibacterial activity was found.     

Synthesis and in vitro antibacterial activity of novel methylamino piperidinyl oxazolidinones

Design and synthesis of a few novel methylamino piperidinyl substituted oxazolidinones are reported. Their antibacterial activities have been evaluated in a MIC assay against broader panel of both susceptible and resistant Gram-positive strains. (S)-N-{3-[3-Fluoro-4-(methyl-{1-[3-(5-nitrofuran-2-yl)-acryloyl]-piperidin-4-yl}-amino)-phenyl]-2-oxo-oxazolidin-5-ylmethyl}-acetamide 4i has shown comparable antibacterial activity to linezolid and eperezolid in the MIC assay, additionally compound 4i showed good antibacterial activity with an in vitro MIC value of 2-4 microg/mL against linezolid resistant Staphylococcus aureus (linezolid 16 microg/mL).     

四种中药对耐药肺炎链球菌的抑菌作用

目的探讨中草药对肺炎链球菌的体外抑菌作用。方法用临床分离细菌为受试菌,采用琼脂稀释法,观察黄连、黄岑、黄柏和连翘等4种中草药水煎剂的最低抑菌浓度。结果4种中草药水煎剂均有不同程度的抑菌作用,其中黄连抑菌效果最好,黄连水煎剂对肺炎链球菌M IC范围达7.8-15.63 g/L,M IC50为8 g/L,M IC90为8 g/L。黄岑、黄柏也有较好的抑菌效果,连翘抑菌效果较弱。结论黄连等中药在体外对肺炎链球菌均有良好抑菌作用。     

Chloropyrimidines as a new class of antimicrobial agents

In the course of our investigations of pyrimidines as antimycotic agents, we have identified a sub-class, with significant in vitro activity against mycobacteria. The salient feature of these pyrimidine derivatives (3a-o and 7a,b) is their appended aryl, heteroaryl and alkylthio substituent at position 6 and also alkylthio substituent at position 2. The rational design, synthesis, and evaluation of the in vitro antibacterial activity against six pathogenic bacteria including virulent and non-virulent strains of Mycobacterium tuberculosis is described. Some of the synthesized compounds (3c, 3h, 3i, 3o) have displayed only potent in vitro antimycobacterial activity with MIC of 0.75 microg/mL except 3i which also demonstrated activity against Escherichia coli at 12.5 microg/mL concentration. Only two compounds, 3a and 3b, demonstrated antibacterial activity against Pseudomonas aeruginosa and E. coli with MIC 12.5 microg/mL. All the synthesized compounds were also evaluated for their antimycotic activity against five pathogenic fungi but only some of them 3j-n and 7a,b were found most potent against Aspergillus fumigatus and Trichophyton mentagrophytes.     

Comparative antibacterial activity of a novel semisynthetic antibiotic: etimicin sulphate and other aminoglycosides

Etimicin is a novel fourth generation semisynthetic aminoglycoside. It has good antimicrobial activity against both gram-positive and gram-negative bacterial infections and also against aminoglycoside resistant strains. In the present study, in vitro antibacterial activity of etimicin was determined by minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC) and time kill curve tests against type strains and 407 clinical isolates (obtained in a surviellance study), in comparison to other aminoglycosides. Test results revealed that etimicin has potential antimicrobial activity and MIC, MBC values for etimicin were low compared to other aminoglycosides. In MBC test etimicin has exhibited potential bactericidal effect ranging from 0.25 to 2?mg/L. The time kill-curve study further demonstrated the rapid, concentration dependent killing and comparative study showed etimicin to exhibit long and effective bactericidal activity over amikacin. The interesting fact is that most of the tested aminoglycoside resistant clinical isolates were susceptible to etimicin. In view of its potent in vitro antibacterial activity and efficacy profiles, it can be concluded that etimicin can be a potent injectable agent for the treatment of severe bacterial infections.     

The synthesis and antibacterial activity of totarol derivatives. Part 1: modifications of ring-C and pro-drugs.

A series of analogues of, and potential pro-drugs derived from, the potent antibacterial diterpene totarol (1) were synthesized in order to elucidate the minimum structural requirements for antibacterial activity and to seek compounds with good bioavailability in vivo. These analogues varied in the structural features of their aromatic rings and the prodrugs were O-glycosylated derivatives. They were tested in vitro against three gram-positive bacteria: beta-lactamase-positive and high level gentamycin-resistant Enterococcus faecalis, penicillin-resistant Streptococcus pneumoniae, and methicillin-resistant Staphylococcus aureus (MRSA); and against the gram-negative multi-drug-resistant Klebsiella pneumoniae. None of the analogues was more potent than totarol itself, which is effective against these gram-positive bacteria at MIC values of 7 microM. The results were evaluated in terms of a structure-activity relationship and this showed that a phenolic moiety was essential for potent antibacterial activity. Amongst the pro-drugs, totaryl alpha-D-mannopyranoside (22) proved the most active in vitro (MIC 18 microM). The in vivo antibacterial activities of compounds 1, 22 and totarol beta-lactoside (23) were assessed in a mouse model of infection, but they were found to be ineffective. Compounds 1 and 22 were shown to be cytotoxic towards proliferating human cell cultures, CH 2983, HeLa, and MG 63, but only at concentrations of > 30 microM.     

Synthesis and antibacterial activity of some aryloxy/thioaryloxy oxazolidinone derivatives

A series of aryloxy/thioaryloxy oxazolidinone derivatives has been synthesized and tested for in vitro antibacterial activity by MIC determination against a panel of susceptible and resistant Gram-positive and Gram-negative microorganisms, some of which are resistant to methicillin and vancomycin. Compounds 12a, 12b, 14a, and 14b from this series were found to be equipotent or more potent than linezolid in vitro.     

Effect of hydrogen peroxide on antibacterial activities of Canadian honeys

Honey is recognized as an efficacious topical antimicrobial agent in the treatment of burns and wounds. The antimicrobial activity in some honeys depends on the endogenous hydrogen peroxide content. This study was aimed to determine whether honey's hydrogen peroxide level could serve as a honey-specific, activity-associated biomarker that would allow predicting and assessing the therapeutic effects of honey. Using a broth microdilution assay, I analyzed antibacterial activities of 42 Canadian honeys against two bacterial strains: Escherichia coli (ATCC 14948) and Bacillus subtilis (ATCC 6633). The MIC90 and MIC50 were established from the dose-response relationship between antibacterial activities and honey concentrations. The impact of H2O2 on antibacterial activity was determined (i) by measuring the levels of H2O2 before and after its removal by catalase and (ii) by correlating the results with levels of antibacterial activities. Canadian honeys demonstrated moderate to high antibacterial activity against both bacterial species. Both MIC90 and MIC50 revealed that the honeys exhibited a selective growth inhibitory activity against E. coli, and this activity was strongly influenced by endogenous H2O2 concentrations. Bacillus subtilis activity was marginally significantly correlated with H2O2 content. The removal of H2O2 by catalase reduced the honeys' antibacterial activity, but the enzyme was unable to completely decompose endogenous H2O2. The 25%-30% H2O2 "leftover" was significantly correlated with the honeys' residual antibacterial activity against E. coli. These data indicate that all Canadian honeys exhibited antibacterial activity, with higher selectivity against E. coli than B. subtilis, and that these antibacterial activities were correlated with hydrogen peroxide production in honeys. Hydrogen peroxide levels in honey, therefore, is a strong predictor of the honey's antibacterial activity.     

The potent antibacterial activity of Sitafloxacin against fluoroquinolone-resistant clinical isolates of Vibrio cholerae O1

The in vitro antibacterial activity of sitafloxacin using clinical isolates of Vibrio cholerae O1 was compared to other fluoroquinolones: ciprofloxacin, ofloxacin, sparfloxacin and levofloxacin. Against fluoroquinolone-resistant O1 strains, sitafloxacin was 4- to 16-fold more effective than other fluoroquinolones at MIC(90*). Against fluoroquinolone-susceptible O1 strains, the MIC(90) of sitafloxacin was 2- to 4-fold lower than other fluoroquinolones. This suggests sitafloxacin can be used in the treatment of infections caused by V. cholerae O1 strains including the fluoroquinolone-resistant strains.     

几种中药单体和抗生素对嗜水气单胞菌及温和气单胞菌的体外抑菌活性研究

考察没食子酸等6种中药单体和诺氟沙星等3种抗生素对嗜水气单胞菌及温和气单胞菌的体外抑菌活性及其联合抑菌作用。通过琼脂扩散法测定受试物的抑菌作用,用微量二倍稀释法测定受试物最小抑菌浓度（MIC）和最小杀菌浓度（MBC）,用棋盘法考察受试物的联合抑菌作用。6种中药单体中没食子酸和槲皮素对嗜水气单胞菌及温和气单胞菌抑制作用较强,抑菌圈均达到20 mm以上,没食子酸对嗜水气单胞菌及温和气单胞菌的MIC和MBC均为250 g/mL;槲皮素对嗜水气单胞菌的MIC和MBC均为500 g/mL,对温和气单胞菌的MIC和MBC分别为250和500 g/mL;而大黄素甲醚等4种中药单体无明显的抑菌作用。嗜水气单胞菌及温和气单胞菌对诺氟沙星、恩诺沙星、氟苯尼考等抗生素均极敏感。在联合药敏试验中,没食子酸与恩诺沙星或氟苯尼考、槲皮素与氟苯尼考联合用药对嗜水气单胞菌具有相加抑菌作用;没食子酸与恩诺沙星联合用药对温和气单胞菌具有协同抑菌作用,没食子酸与诺氟沙星或氟苯尼考、槲皮素与氟苯尼考联合用药对温和气单胞菌具有相加抑菌作用。没食子酸和槲皮素对嗜水气单胞菌及温和气单胞菌具有显著的抑制作用,二者与恩诺沙星、诺氟沙星、氟苯尼考等抗生素联合应用具有相加或协同作用,有助于降低抗生素的用量及残留。       

Antibacterial activity of aerial parts as well as in vitro raised calli of the medicinal plant Saraca asoca (Roxb.) de Wilde

Leaves, stem, and flowers of Saraca asoca, an endangered medicinal plant in India, and young explants cultivated on Murashige & Skoog's medium containing 6-benzylaminopurine were analyzed for antibacterial potential. Alcoholic and aqueous extracts from parent explants and their in vitro raised calli were tested by an agar well diffusion method. Minimal inhibitory concentrations (MICs) of the extracts were determined by broth microdilution method. Aqueous extracts showed antibacterial activity against limited bacterial species, whereas alcoholic extracts were active against a wider range of bacteria. Although the alcoholic extracts of all the explants and calli showed antibacterial activity, the extracts derived from flowers and their calli showed better results. Extracts derived from calli showed comparable results to the extracts from explants. Overall, the MICs of the extracts ranged from 0.039 to 1.25 mg/mL. MICs against gram-positive bacteria ranged from 0.078 to 1.25 mg/mL, whereas they ranged between 0.039 and 0.625 mg/mL against gram-negative bacteria. A MIC distribution plot showed that gram-negative bacteria were more susceptible to the extracts than gram-positive bacteria. It is concluded that extracts of S. asoca contain antibacterial agent, and as the calli gave good results, in vitro cultivation of the explants may be used to obtain antibacterial compounds. This is the first report on antibacterial activity of S. asoca, especially through in vitro raised calli.     

Enhanced clearing of Helicobacter pylori after omeprazole plus roxithromycin treatment

The in vitro antibacterial activity of omeprazole against eight strains of Helicobacter pylori was evaluated. Minimum inhibitory concentration (MIC) values were 32 micrograms/ml and 64 micrograms/ml (MIC50 and MIC90 respectively). We performed a randomized single blind study comparing the efficacy of omeprazole alone (for 4 weeks) or combined with roxithromycin (for 2 weeks) in the treatment of duodenal ulcer and chronic active gastritis associated with H. pylori infection, H. pylori was eradicated in 75% of patients treated with omeprazole alone whereas the patients treated with the combination of these drugs were completely free from H. pylori at the end of the therapy.     

Preparation and antibacterial activity of chitosan nanoparticles

Chitosan nanoparticles, such as those prepared in this study, may exhibit potential antibacterial activity as their unique character. The purpose of this study was to evaluate the in vitro antibacterial activity of chitosan nanoparticles and copper-loaded nanoparticles against various microorganisms. Chitosan nanoparticles were prepared based on the ionic gelation of chitosan with tripolyphosphate anions. Copper ions were adsorbed onto the chitosan nanoparticles mainly by ion-exchange resins and surface chelation to form copper-loaded nanoparticles. The physicochemical properties of the nanoparticles were determined by size and zeta potential analysis, atomic force microscopy (AFM), FTIR analysis, and XRD pattern. The antibacterial activity of chitosan nanoparticles and copper-loaded nanoparticles against E. coli, S. choleraesuis, S. typhimurium, and S. aureus was evaluated by calculation of minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC). Results show that chitosan nanoparticles and copper-loaded nanoparticles could inhibit the growth of various bacteria tested. Their MIC values were less than 0.25 microg/mL, and the MBC values of nanoparticles reached 1 microg/mL. AFM revealed that the exposure of S. choleraesuis to the chitosan nanoparticles led to the disruption of cell membranes and the leakage of cytoplasm.     

Molecular weight and pH effects of aminoethyl modified chitosan on antibacterial activity in vitro

Aminoethyl modified chitosan derivatives (AEMCSs) with different molecular weight (Mw) were synthesized by grafting aminoethyl group on different molecular weight chitosans and chitooligosaccharide. FTIR, (1)H NMR, (13)C NMR, elemental analysis and potentiometric titration results showed that branched polyethylimine chitosan was synthesized. Clinical Laboratory Standard Institute (CLSI) protocols were used to determine MIC for Gram-negative strain of Escherichia coli under different pH. The antibacterial activity of the derivatives was significantly improved compared with original chitosans, with MIC values against E. coli varying from 4 to 64 μg/mL depending on different Mw and pH. High molecular weight seems to be in favor of stronger antibacterial activity. At pH 7.4, derivatives with Mw above 27 kDa exhibited equivalent antibacterial activity (16 μg/mL), while oligosaccharide chitosan derivative with lower Mw (~1.4 kDa) showed decreased MIC of 64 μg/mL. The effect of pH on antibacterial activity is more complicated. An optimal pH for HAEMCS was found around 6.5 to give MIC as low as 4 μg/mL, while higher or lower pH compromised the activity. Cell integrity assay and SEM images showed evident cell disruption, indicating membrane disruption may be one possible mechanism for antibacterial activity.     

家蝇幼虫分泌物抗菌肽的生化特性初步研究

研究了不同温度、蛋白酶及反复冻溶对家蝇 Musca domestica 幼虫活体浸泡法获得的分泌物抗菌肽抗菌活性的影响;并检测其凝血效应;试管稀释法测定其最低抑菌浓度（MIC）、最低杀菌浓度（MBC）;SDS-PAGE分析其分子量范围。结果表明,该抗菌肽具有较强的热稳定性、酶稳定性及较强抗菌活性的特性,无凝血作用。对大肠埃希菌的最低抑菌浓度为37 μg/mL、最低杀菌浓度为75 μg/mL;分子量约10 kD。     

家蝇幼虫抗菌肽的抗菌谱及其与抗生素的协同作用研究

研究3种家蝇幼虫抗菌肽的抗菌谱以及每种抗菌肽的最小抑菌浓度(MIC),初步探讨3种抗菌肽分别与青霉素、链霉素相结合后对抗菌活性的影响,并采用分级抑制浓度指数(Fractionalinhibitoryconcentrationindex,FIC)来定量检测抗菌肽与抗生素之间的抗菌作用关系。结果表明3种抗菌肽的抗菌谱不同,不同的抗菌肽对不同病原菌的抗菌活性不同。3种抗菌肽与链霉素、青霉素之间的抗菌协同关系因细菌种类不同。抗菌肽与抗生素之间并不是都存在协同关系,有些不相关,甚至表现为对抗关系,表明抗菌肽、抗生素与细菌三者的相互作用关系非常复杂。     

In Vitro Antibacterial Activity of 4-Phenyl-1-(2-phenyl-allyl)pyridinium bromide: A Novel Class of Pyridinium Based Antibacterial Compounds

The continuing increase in the incidence of multi drug resistant pathogenic bacteria and shortage of new antimicrobial agents are the prime driver in efforts to identify the novel antimicrobial classes. In vitro antibacterial activity of 4-phenyl-1-(2-phenylallyl) pyridinium bromide was tested against Gram positive Staphylococcus aureus, Streptococcus species, Bacillus subtilis, and Gram negative Klebsiella aerogenes and Escherichia coli using disk diffusion method. Among them S. aureus showed strong antibacterial activity (21.99 ± 0.03 mm) while E. coli showed very little activity (8.97 ± 0.06 mm) towards the compound. The MIC of 4-phenyl-1-(2-phenyl-allyl)-pyridinium bromide for 90% S. aureus was ≤20 μg/ml and was compared with phenoxymethylpenicillin, cloxacillin, erythromycin and vancomycin. When 4-phenyl-1-(2-phenyl-allyl)pyridinium bromide showed MIC at ≤20 μg/ml, all others showed MIC at ≤100 μg/ml. Strong antibacterial activity of 4-phenyl-1-(2-phenyl-allyl)pyridinium bromide against S. aureus indicates that there is a possibility to use it as an effective antibacterial agent.     

4-Alkyl and 4,4'-dialkyl 1,2-bis(4-chlorophenyl)pyrazolidine-3,5-dione derivatives as new inhibitors of bacterial cell wall biosynthesis

Over 195 4-alkyl and 4,4-dialkyl 1,2-bis(4-chlorophenyl)pyrazolidine-3,5-dione derivatives were synthesized, utilizing microwave accelerated synthesis, for evaluation as new inhibitors of bacterial cell wall biosynthesis. Many of them demonstrated good activity against MurB in vitro and low MIC values against gram-positive bacteria, particularly penicillin-resistant Streptococcus pneumoniae (PRSP). Derivative 7l demonstrated antibacterial activity against both gram-positive and gram-negative bacteria. Derivatives 7f and 10a also demonstrated potent nanomolar Kd values in their binding to MurB.     

Synthesis and in vitro activity of novel isoxazolyl tetrahydropyridinyl oxazolidinone antibacterial agents

A series of isoxazolyl tetrahydropyridinyl oxazolidinones with various substituents at the 3-position of the isoxazole ring have been synthesized and their in vitro antibacterial activities (MIC) were evaluated against several Gram-positive strains including the resistant strains of Staphyloccus and Enterococcus, such as MRSA and VRE. One of the most potent compounds synthesized, 4f, showed comparable or better activity against selected bacterial strains than those of linezolid and vancomycin.