Design and synthesis of biologically active cationic amphiphiles built on the calix[4]arene scaffold.

A promising strategy to design safer and more effective cationic lipids for gene delivery with inherent antibacterial properties is to covalently tether a lipophilic moiety with oligomeric aminoglycosides (AGs), a large family of Gram-negative-active antibiotics. Herein, we reported the development of a new class of multicationic-head AG-based amphiphiles built on the tetramino-tetrahexyloxycalix[4]arene (4A4Hex-calix-calix[4]) scaffold. Three different conjugates, namely 4A4Hex-calix-calix[4]-neomycin, -neamine, and -paromomycin, were synthesized and characterized. Due to the inherent multivalency of AGs and the amphiphilic behaviour, every 4A4Hex-calix-calix[4]-AG exhibited greater DNA binding ability than the gold standard transfectant 25 kDa bPEI and striking DNA packing ability. DNA/4A4Hex-calix-calix[4]-AG complexes at charge ratios (CRs, +/-) used for transfections displayed good colloidal stability, with a hydrodynamic diameters of ≈150 nm and an overall surface charges of ≈+30 mV. DNA/4A4Hex-calix[4]-AGs nanoassemblies, everyone tested at the optimal CR, invariably showed good transfection efficiency in two cell lines, along with low-to-negligible cytotoxicity. Besides, DNA/4A4Hex-calix-calix[4]-AG complexes exhibited appreciable antimicrobial activity against Gram-negative bacteria, even greater than uncomplexed 4A4Hex-calix-calix[4]-AGs. Altogether, these results disclose 4A4Hex-calix[4]-AGs as promising gene delivery tools with unique antibacterial properties.

Sarcina ventriculi : Review of the Literature.

Sarcina ventriculi is an increasingly common gram-positive coccus, recognized in gastric biopsies, particularly of patients with delayed gastric emptying. It occurs most commonly in adult women and can be identified easily by its characteristic morphologic features, such as basophilic staining, cuboid shape, tetrad arrangement, red blood cell-sized packets, flattened cell walls, and refractile nature on light microscopy. Although the pathogenesis of the organism is debated, it has been implicated in cases of gastric perforation, emphysematous gastritis, and peritonitis as well as occurring in the background of gastric adenocarcinomas. This review of the literature discusses the clinical features, endoscopy findings, histopathology, ancillary studies, microbiology, pathogenesis, differential diagnosis, treatment, and prognosis of this bacterium based on 19 published cases.

α,ß-DIBROMOCHALCONE DERIVATIVES--SYNTHESIS AND ANTIMICROBIAL ACTIVITY.

AIM: To obtain some chalcones and their dibrominated analogues and to evaluate their antimicrobial potential. MATERIAL AND METHODS: Eight chalcones were synthesized using the Claisen-Schmidt condensation of acetophenone/4-bromo-acetophenone and different benzaldehyde derivatives. These chalcones were further brominated using two different bromination agents: molecular bromine and pyridinium tribromide. The antimicrobial activity was tested using the disk diffusion method. RESULTS AND DISCUSSIONS: The classical bromination technique was compared to the eco-friendly one using pyridinium tribromide. Pyridinium tribromide bromination did not improve the reaction yields (except for one compound), but it had the advantage of being a stable, non-corrosive and non-toxic salt. The results of the antimicrobial assessment indicated that the bromination of the double bond slightly increased the antimicrobial potential in some cases, but the results obtained during the antimicrobial evaluation were modest, some of the derivatives being active especially on Sarcina lutea ATCC 9341 and Bacillus cereus ATCC 14579. CONCLUSIONS: In this study, eight chalcones and their dibrominated analogues were synthesized, four of the α,ß-dibromochalcones being reported for the first time. Pyridinium tribromide was used as an alternative for liquid bromine, the main advantage of this method being related to the reduced toxicity of the reagents. The synthesized compounds did not exhibit a very good antimicrobial potential.

Antibacterial activity of Nymphaea nouchali (Burm. f) flower.

BACKGROUND: The present work aimed to find out the antibacterial activity of Nymphaea nouchali flower on human and plant pathogenic bacteria. METHODS: Antibacterial potency of methanol, acetone, ethyl acetate and petroleum spirit extracts of Nymphaea nouchali flower has been tested against four human pathogenic bacteria Bacillus subtilis (FO 3026) Escherichia coli (IFO 3007), Klebsiella pneumonia (ATTC 10031) and Sarcina lutea (IFO 3232) and one plant pathogenic bacterium Xanthomonas campestris (IAM 1671) by disc diffusion assay. Zone of inhibition produced by different extracts against the test bacteria was measured and compared with standard antibiotic disc. RESULTS: Methanol extract possessed better antibacterial activity against two pathogenic bacteria, B. subtilis (FO 3026) and S. lutea (IFO 3232) than commercial antibiotic nalidixic acid. Acetone extract showed moderate sensitivity whereas B. subtilis (FO 3026), S. lutea (IFO 3232) and X. campestris (IAM 1671) showed resistance to ethyl acetate and petroleum spirit extracts. The minimum inhibitory concentrations of various extracts were ranged between 128-2048 µgml-1. CONCLUSIONS: Nymphaea nouchali flower could be a potential candidate for future development of novel broad spectrum antibacterial herbal formulation.

Molecular characterization of a novel antimicrobial peptide from Mytilus coruscus.

Antimicrobial peptides (AMPs) are components of the innate immune responses that form the first line of host defense against pathogens. Marine mussels can produce a surprising abundance of cysteine-rich AMPs pertaining to the defensin, myticin, mytilin and mytimycin families, particularly in the circulating hemocytes. In the current study, we purified and characterized a novel cysteine-rich peptide with remarkable antibacterial activity from Mytilus coruscus and designated with myticusin-1, a 104-amino acid long polypeptide including 10 cysteine residues forming an unusual cysteine pattern. Antimicrobial assays demonstrated that myticusin-1 exhibited stronger anti-microbial properties against Gram-positive bacteria more than Gram-negative bacteria and fungus. Furthermore, myticusin-1 caused significant morphological alterations in both Sarcina luteus and Escherichia coli as shown by transmission electron microscopy (TEM). The cDNA of myticusin-1 was cloned and sequenced from the hemocytes cDNA library of M. coruscus. The mRNA transcripts of myticusin-1 are mainly detected in hemocyte, which indicates that myticusin-1 are specifically synthesized and stored in circulating hemocytes. The expression level of myticusin-1 in hemocytes was up-regulated and reached the highest level at 36 h after S. luteus challenge, which was 20-fold increase compared to that of the control group. These results indicated that myticusin-1 was involved in the host immune response against bacterial infection and might contribute to the clearance of invading bacteria.

Chemical, antioxidant and antimicrobial investigations of Pinus cembra L. bark and needles.

The chemical constituents and biological activity of Pinus cembra L. (Pinaceae), native to the Central European Alps and the Carpathian Mountains, are not well known. The aim of the present work was to examine the phenolic content, antioxidant and antimicrobial effects of hydromethanolic extracts of Pinus cembra L. bark and needles. Bark extract had higher concentrations of total phenolics (299.3 vs. 78.22 mg gallic acid equivalents/g extract), flavonoids (125.3 vs. 19.84 mg catechin equivalents/g extract) and proanthocyanidins (74.3 vs. 12.7 mg cyanidin equivalents/g extract) than needle extract and was more active as a free radical scavenger, reducing agent and antimicrobial agent. The EC50 values in the 2,2-diphenyl-1-picrylhydrazyl (DPPH), 2,2'-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic acid) diammonium salt (ABTS) and reducing power assays were 71.1, 6.3 and 26 mg/mL for bark extract and 186.1, 24 and 104 mg/mL for needle extract, respectively. In addition, needle extract showed ferrous ions chelating effects (EC50 = 1,755 µg/mL). The antimicrobial effects against Staphylococcus aureus, Sarcina lutea, Bacillus cereus, Escherichia coli, Pseudomonas aeruginosa and Candida albicans were assessed by the agar diffusion method. Both extracts (4 mg/well) were active against all the microorganisms tested; bark extract showed higher inhibition on all strains. These results indicate that Pinus cembra L. bark and needles are good sources of phytochemicals with antioxidant and antimicrobial activities.

[Solution structure and antibacterial mechanism of two synthetic antimicrobial peptides].

Mytilin-derived-peptide-1 (MDP-1) and mytilin-derived-peptide-2 (MDP-2) are two truncated decapeptides with reversed sequence synthesized corresponding to the residues 20-29 of mytilin-1 (GenBank Accession No. FJ973154) from M. coruscus. The objective of this study is to characterize the structural basis of these two peptides for their antimicrobial activities and functional differences, and to investigate the inhibitory mechanism of MDPs on Escherichia coli and Sarcina lutea. The structures of MDP-1 and MDP-2 in solution were determined by 1H 2D NMR methods; the antibactericidal effects of MDPs on E. coli and S. lutea were observed by transmitted electron microscopy (TEM). Both MDP-1 and MDP-2 have a well-defined loop structure stabilized by two additional disulfide bridges, which resemble the-hairpin structure of mytilin-1 model. The surface profile of MDPs' structures was characterized by protruding charged residues surrounded by hydrophobic residues. TEM analysis showed that MDPs destroyed cytoplasmic membrane and cell wall of bacteria and the interface between the cell wall and membrane was blurred. Furthermore, some holes were observed in treated bacteria, which resulted in cell death. Structural comparison between MDP-1 and MDP-2 shows that the distribution of positively charged amino acids on the loop of MDPs is topologically different significantly, which might be the reason why MDP-2 has higher activity than MDP-1. Furthermore, TEM results suggested that the bactericidal mechanisms of MDPs against E. coli and S. lutea were similar. Both MDP-1 and MDP-2 could attach to the negatively charged bacterial wall by positively charged amino acid residues and destroy the bacteria membrane in a pore-forming manner, thus cause the contents of the cells to release and eventually cell death.

HPTLC densitometric evaluation of tissue culture extracts of Nothapodytes foetida compared to conventional extracts for camptothecin content and antimicrobial activity.

Tissue culture technique is becoming popular because of its well-known ability to enhance the content of secondary metabolites in plants. Callus tissue cultures of Nothapodytes foetida were developed using 250 different medium compositions to optimize this procedure. Methanolic extracts of callus (MEC) and of various parts of N. foetida were comparatively analyzed for camptothecin content, and a high performance thin layer chromatography method was developed for its quantitation. Chloroform-ethylacetate-methanol (4 : 5 : 0.5 v/v) was used as the mobile phase. The method was validated for linearity, precision (interday and intraday), repeatability, limit of detection (LOD), limit of quantitation (LOQ), and accuracy. The relationship between the concentration of standard solutions and the peak response was linear within the range of 80 to 480 ng/spot with a correlation coefficient of 0.998 +/- 0.020. Instrumental precision was evaluated as 0.54 (% CV). Repeatability of sample and standard were estimated to be 1.08 and 1.01 (% CV), and LOD and LOQ were found to be 40 and 80 ng/spot, respectively. The accuracy of the method was checked out by a recovery study and the average percentage recovery was calculated as being 99.13 %. The methanolic extract of callus grown in tissue culture with medium composition picloram + thidiazuron + gibberellic acid (1 : 1 : 4; MEC-PTG) showed a higher percentage of camptothecin (5.74 % w/v) than the methanolic extract of fruits (3.56 % w/w), leaves (1.56 % w/w), stem (1.19 % w/w), and root (1.11 % w/w). The results of the antimicrobial screening indicate that MEC-PTG exhibited maximum activity against all microorganisms. Among the fungi tested, MEC-PTG showed maximum activity against A. niger and C. albicans (MIC value 10 microg/mL) whereas among bacteria strains, its activity was highest against B. subtilis and S. lutea (MIC 20 microg/mL).

First solid state alkaline-earth complexes of monensic acid A (MonH): crystal structure of [M(Mon)2(H (2)O)2] (M = Mg, Ca), spectral properties and cytotoxicity against aerobic Gram-positive bacteria.

Alkaline-earth metal complexes of the monoanionic form of the polyether ionophore monensin A were isolated for the first time in solid state and were structurally characterized using various spectroscopic methods (IR, NMR, FAB-MS). The stoichiometric reaction of monensic acid (MonH) with M(2+) (M = Mg, Ca) in the presence of an organic base leads to the formation of mononuclear complexes of composition [M(Mon)(2)(H(2)O)(2)]. The structures of magnesium (1) and calcium (2) monensin complexes in the solid state were established by single crystal X-ray crystallography. The complexes crystallize as [Mg(Mon)(2)(H(2)O)(2)]x5MeCN (1) and [Ca(Mon)(2)(H(2)O)(2)]xH(2)Ox5MeCN (2) in the monoclinic P21 space group. The alkaline-earth metal ion is placed in a distorted octahedral environment, defined by two monensin anions acting as bidentate ligands in the equatorial plane of the complex as well as by two water molecules occupying the axial positions of the inner coordination sphere. The bactericidal activity of 1 and 2 was evaluated against aerobic Gram-positive microorganisms applying the double layer agar hole diffusion method.

Design, synthesis and antibacterial activity of novel actinonin derivatives containing benzimidazole heterocycles.

A series of novel actinonin derivatives containing a benzimidazole heterocycle linked as amide isostere have been designed and synthesized. The structures of all the synthesized compounds were confirmed by analytical and spectroscopic methods. All the compounds were evaluated in vitro against Staphylococcus aureus, Klebsiella pneumoniae, and Sarcina lutea. Among them, compound 1a with unsubstituted benzimidazole ring exhibited potent antibacterial activities.

Synthesis, structure and antimicrobial activity of manganese(II) and cobalt(II) complexes of the polyether ionophore antibiotic Sodium Monensin A.

Mononuclear neutral manganese(II) and cobalt(II) complexes with the antibiotic Sodium Monensin A (Mon-Na, 1b) were synthesized and characterized. The crystal structures of M(Mon-Na)2Cl2.H2O (M=Mn, 2; M=Co, 3) were determined by X-ray crystallography. The complexes crystallize in monoclinic space group C2 with a tetrahedrally coordinated transition metal attached to oxygen atoms of deprotonated carboxyl groups of two Sodium Monensin molecules and two chloride ions. The sodium ion remains in the cavity of the ligand and cannot be replaced by Mn(II) or Co(II). The complexes were additionally characterized by different spectroscopic techniques (UV-Visible, EPR, FAB-MS). A preferable octahedral environment around the transition metal centers is observed in polar solvents while the complexes retain their tetrahedral structure in non-polar media. The antimicrobial activity of 1b, 2 and 3 was tested against Gram(+) and Gram(-) bacteria.

Synthesis and antimicrobial activity of some new 1,3,4-thiadiazole and 1,2,4-triazole compounds having a D,L-methionine moiety.

New 1,3,4-thiadiazole, 5a-e, and 1,2,4-triazolecompounds 6a-c, containing a D,L-methionine moiety were synthesized by intramolecular cyclization of 1,4-disubstituted thiosemicarbazides 4a-e in acid and alkaline media, respectively. The potential antimicrobial effects of the synthesized compounds were investigated using the Staphylococcus aureus ATCC 25923, Bacillus antracis ATCC 8705, Bacillus cereus ATCC 10987, Sarcina lutea ATCC 9341 and Escherichia coli ATCC 25922 strains. The newly synthesized compounds exhibited promising activities against Bacillus antracis and Bacillus cereus.

Antibiotic prophylaxis in cerebrospinal fluid shunting: reassessment of Cefotiam penetration into human CSF.

OBJECTS: Shunt infection is a major complication of shunt implantation. Numerous clinical studies give evidence that antibiotic prophylaxis is efficacious in preventing infections after cerebrospinal fluid shunting. In CSF shunting, antibiotics need to reach sufficient concentrations not only in the blood shielding the operative field but also in tissues and the CSF compartment. Cefotiam is widely used for prophylaxis in neurosurgery. Some clinical trials report that this beta-lactam is able to penetrate considerably into the CSF. However, these studies include disease patterns which are most likely to be associated with a pathological permeability of the blood-brain barrier. Therefore, this study was designed to investigate the extent of penetration of Cefotiam into human CSF in patients without morphological disruption of the blood-brain barrier. METHODS: The penetration of Cefotiam into human CSF was investigated in 23 patients without morphological disruption of the blood-brain barrier undergoing CSF shunt surgery. 2 g Cefotiam was administered prior to surgery as a short-term infusion for a period of 15 min. Samples of blood and CSF were collected intraoperatively. The concentrations of Cefotiam were determined by bioassay. RESULTS: All patients (n=23) showed moderate to high plasma levels of Cefotiam (range: 19.8-146.2 mg/L); the pharmacokinetic profiles in blood accorded well with published data. In contrast to earlier studies, no Cefotiam was detected in CSF. CONCLUSION: This study clearly demonstrates that Cefotiam does not penetrate through an intact blood-brain barrier into human CSF. Although Cefotiam has been shown to be valuable for the perioperative prophylaxis of shunt infection, other antibiotics might be superior if they are capable of entering the CSF. Further studies are required to address this assumption.

Variation in chemical composition and antibacterial activities of essential oils from two species of Houttuynia THUNB.

Houttuynia THUNB. (Saururaceae) has been used for dozens of years in China for the treatment of cough, leucorrhea and ureteritis. The essential oils from the two species: Houttuynia emeiensis and Houttuynia cordata sold in China under one trade name 'Yuxingcao', obtained by hydrodistillation, were analyzed by GC-MS. The results show that fifty-five components were identified and methyl nonyl ketone (2.10-40.36%), bornyl acetate (0.4-8.61%) and beta-myrcene (2.58-18.47%) were the most abundant components in oil, but the percentage of most of compounds in different species and parts varied greatly. The two fold broth dilution and agar dilution method were used to study essential oil of two Houttuynia THUNB. species for their antibacterial properties against microorganisms, Staphylococcus aureus and Sarcina ureae. The two fold dilution method was allowed to determine the minimum inhibitory concentration (MIC) of essential oil from different parts and species. Results showed that all essential oils possessed antibacterial effect, with MIC values in the range of 0.0625 x 10(-3) to 4.0 x 10(-3) ml/ml. However, essential oil from different parts and species differed clearly in their antibacterial activities. The essential oil from the aboveground part of the cultivated Houttuynia emeiensis exhibited higher activity than both parts of the wild and cultivated Houttuynia cordata when used on Staphylococcus aureus (MIC = 0.25 x 10(-3) ml/ml) and Sarcina ureae (MIC = 0.0625 x 10(-3) ml/ml), and had the same activity as the positive control ampicillin sodium.

[Dependence of antimicrobial effect of micelle-capsulated therapeutics on the micelle size].

With the method of dynamic light scattering it was shown that the average size of micelles in the series of formulations based on various clindamycin salts, i. e. ClindHCl+Tween-20, ClindBz+Tween-20, ClindHCl+Cremafor-EL and ClindBz+Cremafor-EL increased from 6 to 20 nm. Investigations with the agar diffusion method revealed that the bactericidic action of the micelle-capsulated therapeutics did not depend on the micelle size within 6 to 20 mn. The concentration of the micellar clindamycin or gentamicin equal to 0.05 mcg/ml was bacteriostatic with respect to Micrococcus (Sarsina) luteus.

[Degree of penetration of antibiotics in the parenhima of the prostate gland].

The article presents results of bacteriological research of a secret of prostate gland and blood serum on test-culture Sercina lutera ATSS 9341 in 57 patients with chronic bacterial prostatitis along with ampicillin sodium application through lymph and intramuscular injection of the antibiotic.

Synthesis and antimicrobial activity of certain novel quinoxalines.

In this study, certain 3-methyl-2-[4-(substituted amino carbonyl)anilino] quinoxalines, (2a-d) and (3a-d), were synthesized from the new key compound 2-[4-(ethoxycarbonyl)anilino]-3-methyl quinoxaline (1). In addition, a series of 2-[4-(arylidene hydrazinocarbonyl)anilino]-3-methyl quinoxalines (5a-e), as well as their cyclized oxadiazolinyl derivatives (6a-e), and a series of 2-[4-N2-acylhydrazinocarbonyl) anilino]-3-methyl quinoxalines (7a-d), as well as their cyclized oxadiazoiyl derivatives (8a-d) were also prepared. Some of these derivatives were evaluated for antimicrobial activity in vitro. It was found that all the selected compounds exhibit antimicrobial activity and that compound 5b had a broad spectrum of activity.

Polycomplexes of poly(acrylic acid) with streptomycin sulfate and their antibacterial activity.

Complex formation between streptomycin sulfate and poly(acrylic acid) has been studied in aqueous solutions by turbidimetric, potentiometric and viscometric methods as well as by FTIR spectroscopy. It was shown that these polycomplexes are stabilized by electrostatic interactions. The solubility of polycomplexes was examined as a function of pH and it was found that at pH values below 3.1 the polycomplexes undergo complete dissociation or dissolution. The antimicrobial activity of the drug and its polycomplex was evaluated using Sarcina sp. as a model organism. It was demonstrated that the polycomplexes have an antimicrobial activity on the same level as the free drug.

Screening of eight alkaloids and ten flavonoids isolated from four species of the genus Boronia (Rutaceae) for antimicrobial activities against seventeen clinical microbial strains.

Eight alkaloids and ten flavonoids isolated from four species of Boronia of the Rutaceae were screened against 17 clinical microbial strains. Of the test compounds, three acridone and one quinolone alkaloids and eight flavonoids were reported as novel natural products. Screening was carried out by the standard disc diffusion method. Of the tested compounds, six alkaloids and seven flavonoids including the novel products were active against six clinical strains. The active compounds showed mild to moderate activities against Bacillus subtilis, Staphylococcus aureus, Sarcina lutea, exterotoxigenic Escherichia coli, Salmonella typhi and Klebsiella sp. Of the active flavonoids, some exhibited fairly significant activity towards Staphylococcus aureus, Sarcina lutea, Salmonella typhi and Klebsiella sp. The flavonoids were observed to have higher spectrum and magnitude of activity than those of the alkaloids. A standard ampicillin disc was used to compare the results.