Metabolism of monoterpene alcohol, linalool, by a soil pseudomonad

A microorganism of the genus Pseudomonas has been isolated from the soil by enrichment culture techniques with linalool(I) as the sole source of carbon and energy. The organism is also capable of utilizing limonene, citronellol, and geraniol as substrates but fails to grow on citral, critranellal, and 1,8-cineole. Fermentation of linalool by this bacterium in a mineral salt medium results in the formation of 10-hydroxylinalool(II), oleuropeic acid (IX), 2-vinyl-2-methyl-5-hydroxyisopropyl-tetraphydrofuran)linalool oxide, V), 2-vinyl-2-methyl-tetrahydrofuran-5-one(unsaturated lactone, VI), and few unidentified minor metabolities. Probable pathways for the biodegradation of linalool are presented.     

Synthesis of 5-chloro-3'-nitro-4'-substituted salicylanilides, a new series of anthelmintic and antimicrobial agents

A number of 5-chloro-3'-nitro-4'-substituted salicylanilides (6--23) have been synthesized by treating 4',5-dichloro-3'-nitrosalicylanilide (5) with various sodium aryl oxides, alkoxides, or amines. These compounds have been tested against Hymenolepis nana infection in rats and have also been evaluated for their in vitro antimicrobial activity against various strains of bacteria and fungi. In the former test 17 was the most active cestodicidal agent showing activity at 30 mg/kg. In the antimicrobial screening, 22 inhibited the growth of all the bacteria and fungi used while 6 was active against the penicillin resistant Staphylococcus aureus at a minimum inhibitory concentration of 0.00609 microgram/mL.     

The form and bioavailability of non-ionic organic chemicals in sewage sludge-amended agricultural soils

The application of sewage sludges to agricultural land may increase the concentrations of many toxic organic chemicals in soils which could have adverse effects on wildlife and human health if these compounds enter foodchains. Chlorobenzenes (CBs), polycyclic aromatic hydrocarbons (PAHs), polychlorinated biphenyls (PCBs) and polychlorinated dibenzo-p-dioxins and furans (PCDD/Fs) are amongst those compounds currently receiving most attention. The "form' in which these, and other organic chemicals, are present in soils and their potential to be lost by various processes including leaching, volatilisation and (bio)degradation is shown to be dependent on the physicochemical characteristics of the soil and sewage sludge, environmental conditions and the properties of the chemicals themselves. The distinction is made between those compounds that are labile, reversibly sorbed and irreversibly sorbed by sewage sludge-amended soils. The implications of the form in which the chemicals are present in soil for their "availability' to transfer from the soil to bacteria, fungi, earthworms, grazing livestock and food crops followed by the potential for further transfers, metabolism or bioaccumulation are discussed. The importance of the timing and method of sewage sludge application to soil on "form' and "availability' are also considered.     

Effect of anti-digoxin monoclonal antibodies on cardiac function disturbances induced by high concentrations of digoxin

Antifungal activities of the compounds isolated from Kalopanax pictus against representative fungi of dermatomycosis were investigated using paper disc diffusion method. It was found that kalopanaxsaponins A and I were effective in inhibiting the growth of Candida albicans KCTC 1940 and Cryptococcus neoformans KCTC 7224 with minimum inhibitory concentration (MIC) of 25 micrograms/ml. It showed that antifungal activity of both compounds have strong selectivity against the fungi of dermatomycosis.     

Purification, characterization, and substrate specificity of a novel highly glucose-tolerant beta-glucosidase from Aspergillus oryzae

Aspergillus oryzae was found to secrete two distinct beta-glucosidases when it was grown in liquid culture on various substrates. The major form had a molecular mass of 130 kDa and was highly inhibited by glucose. The minor form, which was induced most effectively on quercetin (3,3',4',5,7-pentahydroxyflavone)-rich medium, represented no more than 18% of total beta-glucosidase activity but exhibited a high tolerance to glucose inhibition. This highly glucose-tolerant beta-glucosidase (designated HGT-BG) was purified to homogeneity by ammonium sulfate precipitation, gel filtration, and anion-exchange chromatography. HGT-BG is a monomeric protein with an apparent molecular mass of 43 kDa and a pI of 4.2 as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and isoelectric focusing polyacrylamide gel electrophoresis, respectively. Using p-nitrophenyl-beta-D-glucoside as the substrate, we found that the enzyme was optimally active at 50 degreesC and pH 5.0 and had a specific activity of 1,066 micromol min-1 mg of protein-1 and a Km of 0.55 mM under these conditions. The enzyme is particularly resistant to inhibition by glucose (Ki, 1. 36 M) or glucono-delta-lactone (Ki, 12.5 mM), another powerful beta-glucosidase inhibitor present in wine. A comparison of the enzyme activities on various glycosidic substrates indicated that HGT-BG is a broad-specificity type of fungal beta-glucosidase. It exhibits exoglucanase activity and hydrolyzes (1-->3)- and (1-->6)-beta-glucosidic linkages most effectively. This enzyme was able to release flavor compounds, such as geraniol, nerol, and linalol, from the corresponding monoterpenyl-beta-D-glucosides in a grape must (pH 2.9, 90 g of glucose liter-1). Other flavor precursors (benzyl- and 2-phenylethyl-beta-D-glucosides) and prunin (4',5,7-trihydroxyflavanone-7-glucoside), which contribute to the bitterness of citrus juices, are also substrates of the enzyme. Thus, this novel beta-glucosidase is of great potential interest in wine and fruit juice processing because it releases aromatic compounds from flavorless glucosidic precursors.     

Synthesis and biological evaluation of a series of substituted pyrazolo[3,4-d]-1,2,3-triazoles and pyrazolo[3,4-d]oxazoles

In view of the biological relevance of triazole-based heterocyclic structures as antifungal, antiviral, and antitumor agents, we have synthesized a series of substituted pyrazolo[3,4-d]-1,2,3-triazoles (2e-h, 2j, 4b) which we evaluated for their cytostatic and antiviral (HIV-1 included) activity and for their capability to inhibit the multiplication of various human pathogenic fungi and bacteria. Moreover, the biological activities of a few compounds, namely pyrazolo[3,4-d]oxazoles (3a-e) and pyrazolo[3,4-d]-1,2,3-triazoles (2a-d, 4a, 5), previously obtained by us but not investigated for their biological activity, were also studied. Only compounds 3a-e were endowed with a significative antiproliferative activity on the human lymphoblastoid cell line MT-4 cells. All pyrazole derivatives proved ineffective in protecting cell cultures against the HIV-1-induced cytopathogenicity, and none of the compounds was active against the bacteria and fungi tested.     

GC-MS analysis of essential oils from the pericarps of Illicium majus Hook.f.et. Thoms. and I. micranthum Dunn

The chemical constituents of essential oils from the pericarps of Illicium majus and I. micranthum were analyzed. Seventy-two compounds have been identified by GC-MS, of which safrole, linalool and limonene are higher in content.     

Heparan sulfate staining of the glomerular basement membrane in relation to circulating anti-DNA and anti-heparan sulfate reactivity: a longitudinal study in NZB/W F1 mice

BACKGROUND: Pyroglyphid mites are considered a major cause of house dust allergy. The occurrence and possible pathogenic role of other biologic components of house dust, in particular bacteria, has received less attention. OBJECTIVE: The aim of this study was to examine bacteria present in the samples of house dust from beds, in comparison to fungi and mites recovery. METHODS: Samples of bed dust were collected from 40 homes in Upper Silesia (Poland). Of these, 19 came from the homes of people with asthma caused by house dust and 21 from the homes of people without allergy. The concentrations of bacteria, fungi, mites, and endotoxin and species composition of microflora and acarofauna were determined. RESULTS: The overall mean concentrations of mesophilic bacteria, thermophilic bacteria and fungi, including yeasts, were, respectively, 1.6 x 10(6), 1.7 x 10(3), and 1.6 x 10(4) CFU/g. Samples contained an average of 8.4 mites/g and the ten samples assayed for bacterial endotoxin averaged 80.4 ng/mg. A total of 55 species of bacteria, 40 of fungi and 13 of mites were found. Gram-positive cocci (mostly Staphylococcus spp.) were the predominant mesophilic bacteria, followed by corynebacteria and Bacillus spp. Thermophilic bacteria were represented only by actinomycetes, with Thermoactinomyces vulgaris predominant. The most numerous fungi were Penicillium spp. and Aspergillus spp. followed by yeasts. The most abundant mites were Dermatophagoides spp. which formed > 85% of the total count. There were no significant differences between the homes of allergic and nonallergic people in the concentrations of total bacteria, fungi, and mites. Bacillus, Aspergillus and total filamentous fungi (molds), but not yeasts, were significantly more numerous in the homes of people with asthma caused by house dust. CONCLUSION: The results suggest that some species of bacteria and filamentous fungi should be considered potential causes of house dust allergy.     

Protective effects of a culture supernatant of Lactobacillus acidophilus and antioxidants on ileal ulcer formation in rats treated with a nonsteroidal antiinflammatory drug

Ileal ulcers and thiobarbituric acid (TBA)-reactive substances in the ileal mucosa were induced in rats treated with a nonsteroidal antiinflammatory drug, 5-bromo-2-(4-fluorophenyl)-3-(4-methylsulfonylphenyl)thiophene (BFMeT), at a dose of 1,000 mg/kg administered with tap water as drinking water. However, the formation of ileal ulcers and TBA-reactive substances in the ileal mucosa was repressed by giving the animals a culture supernatant of Lactobacillus acidophilus as drinking water. We measured the antioxidative activity of the culture supernatant and found that the supernatant inhibited the formation of t-butyl hydroperoxide-induced TBA-reactive substances in erythrocyte membrane ghosts. Therefore, the effects of various known antioxidative compounds on the ileal ulcer formation induced by BFMeT were investigated. While alpha-tocopherol, t-butyl-1,4-hydroxyanisole and allopurinol did not repress ulcer formation after BFMeT treatment, ascorbic acid, dimethyl sulfoxide, glutathione and beta-carotene significantly inhibited formation. Among these compounds, ascorbic acid was the most effective. Accumulation of TBA-reactive substances in the ileal mucosa after BFMeT treatment also decreased significantly in rats treated with ascorbic acid. In addition, the percentage of gram-negative rods in the ileal contents of rats treated with BFMeT and tap water was dramatically increased, but it was not increased in rats treated with BFMeT and these antioxidants. A positive correlation between the percentage of gram-negative rods and the number of ileal ulcers was also observed. These results suggest that lipid peroxidation mediated by oxygen radicals plays an important role in the induction of ileal ulcers by BFMeT in rats, and that lipopolysaccharide-activated neutrophils probably produce highly reactive hypochlorous acid and hydrogen peroxide, which are inactivated by ascorbic acid and glutathione, respectively.     

Reversal of methylcholanthrene-induced changes in mouse prostates in vitro by retinoic acid and its analogues

The influence of vitamin A-related compounds on hyperplasia and metaplasia induced by methylcholanthrene was studied in mouse prostate glands in organ culture. Methylcholanthrene was found to cause extensive hyperplasia and squamous metaplasia of the prostatic epithelium which persisted after withdrawal of the carcinogen. The retinoids included retinoic acid and 6 of its structural analogues synthesized in an attempt to enhance the anticarcinogenic action and reduce the toxicity of the parent compound. These where the cyclopentenyl analogus 7699, A2-retinoic acid, 13-cis-alpha-retinoic acid and 3 aromatic analogues. Administration of the compounds following the carcinogen reduced the extent and incidence of hyperplasia significantly and with the exception of one compound reversed the squamous metaplasia. Two of the aromatic analogues, one with a terminal ethylamide group (1430), and the other with a terminal ethylester group (9369), proved to be the most potent inhibitors, followed by compound 7699 and (9369), proved to be the most potent inhibitors, followed by compound 7699 and retinoic acid. A2-retinoic acid and 13-cis-alpha-retinoic acid showed the lowest activity. The inhibition of hyperplasia appeared to be mediated via a reduction of DNA synthesis. It seemed unrelated to either the biological growth-promoting activity of the compounds or their surface-active properties. It is tentatively suggested that vitamin A and its analogues may act as hormones.     

Biotransformation of all-trans-retinal, 13-cis-retinal, and 9-cis-retinal catalyzed by conceptal cytosol and microsomes

Oxidative conversions of all-trans-retinal (t-RAL), 13-cis-retinal (13-cRAL), and 9-cis-retinal (9-cRAL) to their corresponding retinoic acids (RAs) catalyzed by rat conceptal cytosol (RCC) or microsomes (RCM) were studied. The primary product of RCC-catalyzed oxidations of both t-RAL and 13-cRAL was t-RA, with only trace amounts of 13-cRA and 9-cRA. In the RCC-catalyzed oxidation of 9-cRAL, generated t-RA, 9-cRA, and 13-cRA constituted approximately 56, 34, and 10%, respectively, of the total RAs. For all RCC-catalyzed retinal oxidations, NAD was a much more effective cofactor than NADP. And t-RAL and 13-cRAL were much better substrates than 9-cRAL. Formaldehyde, acetaldehyde, citral, and disulfiram were investigated as inhibitors, but only citral and disulfiram effectively inhibited the RCC-catalyzed conversion of t-RAL or 13-cRAL to t-RA. Methanol and ethanol failed to inhibit either reaction even at very high concentrations (> or = 10 mM). RCM exhibited lower specific enzymatic activities than RCC in catalyzing oxidations of t-RAL, 13-cRAL, and 9-cRAL, indicating that the cytosolic fraction was dominant for converting retinals to RAs. The predominant RA produced from RCM-catalyzed oxidations of t-RAL, 13-cRAL, or 9-cRAL was t-RA for each substrate, and again NAD was a much more effective cofactor than NADP in all cases. For RCM-catalyzed oxidations of RALs, 13-cRAL was a much better substrate than t-RAL or 9-cRAL. Methanol and ethanol were not effective inhibitors for RCM-catalyzed oxidations of t-RAL or 13-cRAL. In RCM-catalyzed reactions, citral (10 mM) completely inhibited oxidation of t-RAL but showed only a minor effect on oxidation of 13-cRAL. 13-cRA was converted almost completely to t-RA after 2 hr of incubation with RCC.     

GC-MS analysis of essential oils from pericarps of Illicium brevistylum A. C. Smith and I. jiadifengpi B.N. Chang

The chemical constituents of essential oils from the pericarps of illicium brevistylum and I. Jiadifeng pi were analyzed. Sixty-six compounds have been identified by GC-MS, of which limonene and linalool are higher in content. The essential oil of I. brevistylum has been found rich in 1, 8-cineole and terpinen-4-ol.     

Effects of thiols on topoisomerase-II alpha activity and cell cycle progression

Thiol containing compounds exhibiting antioxidant properties are currently being evaluated for use in cytoprotection and chemoprevention. Many of these have also been found to be effective in inhibiting cell cycle progression and cellular proliferation. N-Acetyl-L-cysteine (L-NAC), along with its nonmetabolically active stereoisomer N-acetyl-D-cysteine (D-NAC), together with captopril and dithiothreitol (DTT) were investigated to assess their effects on cell cycle progression as determined by flow cytometry. Topoisomerase-IIa (topo-II alpha) activity, an enzyme involved in DNA synthesis, was also monitored as a function of drug dose using a kinetoplast DNA (kDNA) decatenation assay. Chinese hamster ovary (CHO) AA8 cells were exposed to each thiol at concentrations ranging from 4 microM to 4 mM for a period of 3 h. Following the removal of the thiols, cell cultures were followed for an additional 5 h to assess changes in cell cycle progression. L-NAC, which also serves as a precursor for glutathione (GSH) synthesis, effectively inhibited topo-IIa activity by at least 50% at all concentrations tested. Associated with this reduction in enzyme activity was a sixfold increase in the relative number of cells accumulating in G2phase. D-NAC, which is unable to participate in GSH synthesis, was only half as effective as L-NAC at each concentration tested in inhibiting topo-IIa activity as well as perturbing cell progression through G2. In comparison, captopril, an inhibitor of angiotensin converting enzyme (ACE), had little effect on the progression of cells into G2 phase. In contrast to the repressive effects of L-NAC and D-NAC, it enhanced topo-IIa activity over control values by approximately 20%. DTT, a well characterized thiol known to be capable of reducing disulphides in proteins, was observed to be relatively ineffective in either perturbing cell cycle progression or affecting topo-IIa activity. This suggests an involvement of a mechanism(s) in addition to thiol mediated affects on reduction/oxidation processes. The inhibitory effects of L-NAC and D-NAC on topo-IIa activity, in contrast to the other two thiols, may be due in part to the presence of amine groups which could allow for their participation in polyamine related processes. The difference in the magnitude of the effect exhibited by L-NAC, as compared to D-NAC, on the repression topo-IIa activity also suggests a role for GSH in this process. Inhibition of cellular progression and proliferation by thiols can therefore be mediated by diverse mechanisms which include both cycle-phase specific (i.e. L-NAC and D-NAC) and non cell cycle specific (i.e. captopril) processes.     

Modulation of ceramide-activated protein phosphatase 2A activity by low molecular weight aromatic compounds

Protein phosphatase 2A (PP2A) is one of the most important and abundant serine/threonine phosphatases in mammalian tissues and plays a role in gene expression, cell division, and signal transduction. PP2A is activated by ceramide, which is produced by the hydrolysis of membrane sphingomyelin in response to a variety of stress-related stimuli. To further study the role of ceramide-mediated signal transduction in cellular processes such as senescence and apoptosis, we designed and synthesized a series of low molecular weight aromatic compounds, mainly of the isoquinolone and tetralone classes, and evaluated their ability to inhibit enzymes known to be activated by ceramide. Those enzymes studied were ceramide-activated protein kinase, protein kinase C zeta and PP2A. Of these, only PP2A was found to be inhibited. A few of the compounds inhibited both ceramide-activated as well as basal PP2A activity. In addition, several of the compounds activated PP2A by up to 300% above basal enzyme activity, but only in the presence of ceramide. Thus, modulation (both inhibition and activation) of the catatylic activity of ceramide-activated PP2A is demonstrated by certain low molecular weight aromatic compounds.     

A unique reaction in a common pathway: mechanism and function of chorismate synthase in the shikimate pathway

Chorismate synthase, the seventh enzyme in the shikimate pathway, catalyzes the transformation of 5-enolpyruvylshikimate 3-phosphate to chorismate which is the last common precursor in the biosynthesis of numerous aromatic compounds in bacteria, fungi and plants. The enzyme has an absolute requirement for reduced FMN as a cofactor, although the 1,4-anti elimination of phosphate and the C(6proR)-hydrogen does not involve a net redox change. The role of the reduced FMN in catalysis has long been elusive. However, recent detailed kinetic and bioorganic approaches have fundamentally advanced our understanding of the mechanism of action, suggesting an initial electron transfer from tightly bound reduced flavin to the substrate, a process which results in C-O bond cleavage. Studies on chorismate synthases from bacteria, fungi and plants revealed that in these organisms the reduced FMN cofactor is made available in different ways to chorismate synthase: chorismate synthases in fungi--in contrast to those in bacteria and plants--carry a second enzymatic activity which enables them to reduce FMN at the expense of NADPH. Yet, as shown by the analysis of the corresponding genes, all chorismate synthases are derived from a common ancestor. However, several issues revolving around the origin of reduced FMN, as well as the possible regulation of the enzyme activity by means of the availability of reduced FMN, remain poorly understood. This review summarizes recent developments in the biochemical and genetic arena and identifies future aims in this field.     

The effect of new synthetic cholesterol derivatives on cholesterol metabolism in cultured rabbit hepatocytes

The effects of three novel synthetic derivatives of cholesterol with ethoxy (I), aminoethoxy (II), azidoethoxy (III) and toluenesulfonyloxyethoxy (IV) groups in the 3 beta-hydroxy position of cholesterol on cholesterol synthesis as well as on apolipoprotein B and bile acid secretion in cultured rabbit hepatocytes have been studied. 3 beta-(2-hydroxyethoxy)-cholest-5-en (I) was used as a standard. It was found that the inhibiting effect of these compounds on cholesterol synthesis depends on their structure. Compound II (1 microgram/ml), which inhibited acetate incorporation into cholesterol by 30-50%, appeared to be the most effective among the other compounds tested. This derivative had no effect on the production of bile acids. Compound III was less effective, while compound IV had no effect on cholesterol synthesis. All the compounds under study reduced by 20-36% the secretion of the total apolipoprotein B as measured by the enzyme-linked immunosorbent assay (ELISA). None of the synthetic cholesterol derivatives influenced the leucine incorporation into the total protein fraction. The results obtained indicate that 3 beta-(2-aminoethoxy)cholest-5-en, the most effective compound among other cholesterol derivatives tested in the study, can serve as a basis for synthesizing novel cholesterol derivatives able to inhibit cholesterol biosynthesis in liver cells and to decrease the secretion of very low density lipoproteins in cultured rabbit hepatocytes.     

Structural analyses of polymorphic transitions of sn-1, 3-distearoyl-2-oleoylglycerol (SOS) and sn-1, 3-dioleoyl-2-stearoylglycerol (OSO): assessment on steric hindrance of unsaturated and saturated acyl chain interactions

Several compounds that specifically inhibited replication of the H1 and H2 subtypes of influenza virus type A were identified by screening a chemical library for antiviral activity. In single-cycle infections, the compounds inhibited virus-specific protein synthesis when added before or immediately after infection but were ineffective when added 30 min later, suggesting that an uncoating step was blocked. Sequencing of hemagglutinin (HA) genes of several independent mutant viruses resistant to the compounds revealed single amino acid changes that clustered in the stem region of the HA trimer in and near the HA2 fusion peptide. One of the compounds, an N-substituted piperidine, could be docked in a pocket in this region by computer-assisted molecular modeling. This compound blocked the fusogenic activity of HA, as evidenced by its inhibition of low-pH-induced cell-cell fusion in infected cell monolayers. An analog which was more effective than the parent compound in inhibiting virus replication was synthesized. It was also more effective in blocking other manifestations of the low-pH-induced conformational change in HA, including virus inactivation, virus-induced hemolysis of erythrocytes, and susceptibility of the HA to proteolytic degradation. Both compounds inhibited viral protein synthesis and replication more effectively in cells infected with a virus mutated in its M2 protein than with wild-type virus. The possible functional relationship between M2 and HA suggested by these results is discussed.     

Microbial metabolism of pyridine, quinoline, acridine, and their derivatives under aerobic and anaerobic conditions

Our review of the metabolic pathways of pyridines and aza-arenes showed that biodegradation of heterocyclic aromatic compounds occurs under both aerobic and anaerobic conditions. Depending upon the environmental conditions, different types of bacteria, fungi, and enzymes are involved in the degradation process of these compounds. Our review indicated that different organisms are using different pathways to biotransform a substrate. Our review also showed that the transformation rate of the pyridine derivatives is dependent on the substituents. For example, pyridine carboxylic acids have the highest transformation rate followed by mono-hydroxypyridines, methylpyridines, aminopyridines, and halogenated pyridines. Through the isolation of metabolites, it was possible to demonstrate the mineralization pathway of various heterocyclic aromatic compounds. By using 14C-labeled substrates, it was possible to show that ring fission of a specific heterocyclic compound occurs at a specific position of the ring. Furthermore, many researchers have been able to isolate and characterize the microorganisms or even the enzymes involved in the transformation of these compounds or their derivatives. In studies involving 18O labeling as well as the use of cofactors and coenzymes, it was possible to prove that specific enzymes (e.g., mono- or dioxygenases) are involved in a particular degradation step. By using H2 18O, it could be shown that in certain transformation reactions, the oxygen was derived from water and that therefore these reactions might also occur under anaerobic conditions.     

In vitro antifungal and fungicidal activities and erythrocyte toxicities of cyclic lipodepsinonapeptides produced by Pseudomonas syringae pv. syringae

Recent increases in fungal infections, the few available antifungal drugs, and increasing fungal resistance to the available antifungal drugs have resulted in a broadening of the search for new antifungal agents. Strains of Pseudomonas syringae pv. syringae produce cyclic lipodepsinonapeptides with antifungal activity. The in vitro antifungal and fungicidal activities of three cyclic lipodepsinonapeptides (syringomycin E, syringotoxin B, and syringostatin A) against medically important isolates were evaluated by a standard broth microdilution susceptibility method. Erythrocyte toxicities were also evaluated. All three compounds showed broad antifungal activities and fungicidal actions against most of the fungi tested. Overall, the cyclic lipodepsinonapeptides were more effective against yeasts than against the filamentous fungi. Syringomycin E and syringostatin A had very similar antifungal activities (2.5 to > 40 micrograms/ml) and erythrocyte toxicities. Syringotoxin B was generally less active (0.8 to 200 micrograms/ml) than syringomycin E and syringostatin A against most fungi and was less toxic to erythrocytes. With opportunities for modification, these compounds are potential lead compounds for improved antifungal agents.     

A biomechanical comparison of intramedullary nail and crossed lag screw fixation for tibiotalocalcaneal arthrodesis

A series of Pyrazolo[1,5-a]pyrido[3,4-e]pyrimidin-6-ones (4a-p) was prepared by a simple synthetic procedure based on the reaction of hydroxylamine or methoxyamine with 2,3-substituted ethyl 7-dimethylaminovinyl pyrazolo[1,5-a]pyrimidin-6-carboxylates (3a-p). The antimicrobial activity of the obtained compounds was evaluated on a series of standard strains of Gram positive, Gram negative bacteria and fungi. None of the tested compounds showed significant activity.