In vitro Evaluation of Antifungal Activity of the Seed Extract of Embelia Ribes

Antifungal activity of Embelia ribes was evaluated on eight different fungal species by employing various concentrations of seed extract (0.5-2.0 mg). All the concentrations of seed extract inhibited the fungal growth, whereas maximum activity was observed at 2.0 mg concentration of seed extract. Among different doses, the diameter of inhibition zones ranged from 9 to 18 mm in various fungal species and increased with the increase in the concentration of test solution. Among all the fungi, high inhibition zones were observed in Colletotricum crassipes (18 mm). This was followed by Cladosporium (17.5 mm), Armillaria mellea (17 mm), Colletotricum capsici (17 mm), Aspergillus niger (16.5 mm), Rhizopus oryzae (16.5 mm), respectively. Aspergillus terreus and Candida albicans showed less inhibition zones (15.5 and 16.0 mm) compared to other organisms. The present study clearly demonstrated the antifungal properties of Embelia ribes.     

Antibacterial structure-activity relationships obtained with resistant microorganisms I: Inhibition of R-factor resistant Escherichia coli by tetracyclines.

Aparent partition coefficients and inhibitory activities against sensitive and resistant Escherichia coli were determined for 14 tetracyclines. The difference in the kinetics of inhibition of the two organisms is discussed in terms of their permeabilities. The partition coefficients were determined in an octanol-buffer system. Values for eight compounds were in general agreement with the literature; values for the remaining six compounds had not been reported previously. Growth of the organisms was determined by a single-point turbidimetric method in the presence and absence of tetracyclines. Inhibitory activities were obtained by a kinetic treatment. Derived rate constants for the sensitive organism were linearly related to antibiotic concentration. For the resistant organism and 12 compounds, the derived rate constants and antibiotic concentration were related in a manner typical of saturation kinetics. These inhibitory activities were related to the partition coefficients, while activities against the sensitive strain were not. These findings suggest that activity against the resistant strain is permeability controlled but that activity against the sensitive strain has a different rate-determining step.     

Antifungal and antibacterial activities of different extracts of Harungana madagascariensis stem bark

The antifungal and antibacterial effects of the stem bark extracts of Harungana madagascariensis Lam. ex Poir. (Clusiaceae) were examined against nine microbial pathogens causing infections in both man and animals. Hexane (H), dichloromethane (D), chloroform (C), ethyl acetate (E), acetone (A), methanol (M), and water (W) extracts were tested in vitro through bioautography and minimum inhibitory concentrations (MIC) determination using the serial micro-dilution assays. Bioautographic results revealed the presence of eight different spots. Extract A exhibited the lowest MIC of 0.04?mg/mL against Microsporum canis, while water extract (W) and methanol (M) showed the highest MIC of 2.5?mg/mL against at least one of the tested fungi when compared to amphotericin B with 0.0625–1?g/mL. Sporotrichum schenckii was the most susceptible fungal pathogen with average MIC of 0.06?mg/mL, while the acetone extract (A) was the most active against three fungal organisms when compared with other extracts. Similarly, extracts D, C, E and A exhibited very high activity with low MIC values of 0.156–0.62?mg/mL, while M and W gave the highest values of 0.31–2.5?mg/mL on bacterial pathogens as compared to gentamicin (0.02–0.62 8?g/mL). The dichloromethane extract is the most active against bacteria with average MIC of 0.19?mg/mL, while Staphylococcus aureus is the most sensitive organism; that shows susceptibility at an average MIC of 0.34?mg/mL. These results provide promising information for the potential use of the crude extracts from the stem-bark of H. madagascariensis in the treatment of bacterial and fungal infections similar to what was obtained in the leaves.     

Comparative molecular field analysis of fungal squalene epoxidase inhibitors

Comparative molecular field analysis (CoMFA) of fungal squalene epoxidase inhibitors exhibiting antifungal activity reported in terms of minimum inhibitory concentration (MIC) was performed. Ninety-two molecules belonging to different chemical classes, namely terbinafine analogues, benzylamines, homopropargylamines, and carbon analogues were divided into training set and test set. The initial conformations of the inhibitors obtained from molecular dynamics simulations for 50 ps in aqueous solution were used in the study. Out of three charges used in the study, Gasteiger-H]uckel charges result in models with good internal predictivity. Initial analysis of 92 molecules (analysis A) resulted in models with low predictive r(2) values for activity against three organisms. This data set was modified by exclusion of 13 molecules, and analysis was performed again. This analysis of 79 molecules (analysis B) resulted in improvement in predictivity of the CoMFA models and cross-validated r(2) values of 0.583, 0.509, and 0.502 for Candida albicans, Aspergillus fumigatus, and Trichophyton mentagrophytes, respectively. These models were used to predict the activities of the molecules belonging to the test set. The models from analysis B show better correlative and predictive properties than analysis A. Comparison of CoMFA contour maps for activity against three different fungi revealed differentiating structural requirements.     

In vitro activity of MSI-78 alone and in combination with antibiotics against bacteria responsible for bloodstream infections in neutropenic patients

MSI-78 is a 22 amino acid amphipathic peptide with potent antimicrobial activity against Gram-positive and Gram-negative organisms, including antibiotic-resistant strains. In this study, we assessed the in vitro activity of MSI-78 alone and in combination with eight clinically used antimicrobial agents against several strains of Pseudomonas aeruginosa, Staphylococcus aureus, Staphylococcus epidermidis and Escherichia coli isolated from blood of neutropenic febrile patients. Antimicrobial activity of MSI-78 was measured by minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), time-kill studies and checkerboard titration method. The Gram-negative isolates were susceptible to the peptide at concentrations in the range 0.50-16 mg/L, while staphylococci showed lower susceptibility. MSI-78 demonstrated a higher antimicrobial activity than colistin against Gram-negative organisms. The checkerboard titration method demonstrated synergy when the peptide was combined with beta-lactams. These results provide evidence for the potential use of MSI-78 in the management of severe infections in neutropenic patients.     

A new streptomycete producing diphenyl sulfone antibiotic--S. sulfonensis

About 359 actinomycetes were isolated from 8 different natural substrates collected from different parts of Andhra Pradesh. The isolates were screened on the basis of their inhibitory effect against test organisms. Finally one potent antibiotic producer was chosen having broad-spectrum activity against Gram-positive and Gram-negative bacteria and it was found to produce a diphenyl sulfone antibiotic. On the basis of morphological, cultural, physiological and biochemical characters, the diphenyl sulfone antibiotic producer was identified as a new species and was designated as S. sulfonensis.     

Composition and Antimicrobial Activity of the Essential Oil from Leaves of Curcuma longa L. Kasur Variety

The essential oil from the leaves of Curcuma longa L. Kasur variety grown in Pakistan was extracted by hydro-distillation. Chemical constituents of the essential oil were identified by gas chromatography/mass spectrometry. The chromatographic analysis of oil showed 25 constituents, out of which nine chemical constituents were identified. The eucalyptol (10.27%) was the major component of the essential oil. α-pinene (1.50%), β-phellandrene (2.49%), β-pinene (3.57%), limonene (2.73%), 1,3,8-p-menthatriene (1.76%), ascaridole epoxide (1.452%), 2-methylisoborneol (2.92%), 5-isopropyl-6-methyl-hepta-3, dien-2-ol (2.07%) were also present in considerable quantity. The antimicrobial properties of leaves of Curcuma longa were tested by disc diffusion method against various human pathogens, including eight fungal and five bacterial strains. Essential oil showed maximum resistance against Fusarium miniformes MAY 3629 followed by Bacillus subtilis ATCC 6633 whereas; it exhibited least resistance against Fusarium oxysporium ATCC 48122. The results of the antimicrobial assay revealed that essential oil showed significant inhibitory activity against the tested organisms.     

Structure-specific inhibition of cholesteryl ester transfer protein by azaphilones.

The effect of thirteen different fungal azaphilones, which have a common 6-iso-chromane-like ring, was tested on cholesteryl ester transfer protein (CETP) activity in vitro. Chaetoviridin B showed the most potent inhibitory activity with an IC50 value of < 6.2 microM, followed by sclerotiorin with an IC50 value of 19.4 microM. Rotiorin, chaetoviridin A and rubrorotiorin had moderate inhibitory activity (IC50 ; 30 approximately 40 microM), but others showed very weak or no inhibitory activity. The relationship between the structures and their inhibitory activity indicated that the presence of an electrophilic ketone(s) and/or enone(s) at both C-6 and C-8 positions in the isochromane-like ring is essential for eliciting CETP inhibitory activity. The transfer activity of both CE and TG was inhibited by sclerotiorin to approximately the same extent (IC50: 14.4 and 10.3 microM, respectively). A model of the reaction suggested that sclerotiorin reacts with a primary amine of amino acids such as lysine in the protein to form a covalent bond.     

Biological activity of the tryprostatins and their diastereomers on human carcinoma cell lines

Tryprostatin A 1 and B 2 are indole alkaloid-based fungal products that act in the G2/M phase of the cell cycle. Tryprostatin A and B as well as their two enantiomers and four diastereomers have been synthesized via a common strategy. As a measure of cytotoxicity, these eight stereoisomers were assayed for their growth inhibitory properties in human breast, prostate, and lung cancer cell lines. The ability of the tryprostatins and the tryprostatin stereoisomers to induce topoisomerase II-mediated DNA relaxation or to inhibit tubulin polymerization was also examined. Although none of the stereoisomers were significantly active in topoisomerase II- or tubulin-based assays, ds2-try B 11 was found to exhibit a cytotoxicity profile more potent than etoposide 3 in the human cancer cell lines examined. In addition, ds2-try B 11 is comprised of an L-tryptophan derivative coupled to a D-proline moiety, the latter stereochemistry of which may enhance the activity of 11 and potential analogues in vivo.     

Impact of Absolute Stereochemistry on the Antiangiogenic and Antifungal Activities of Itraconazole

Itraconazole is used clinically as an antifungal agent and has recently been shown to possess antiangiogenic acitivity. Itraconazole has three chiral centers that give rise to eight stereoisomers. The complete role of stereochemistry in the two activities of itraconazole, however, has not been addressed adequately. For the first time, all eight stereoisomers of itraconazole (1a-1h) have been synthesized and evaluated for activity against human endothelial cell proliferation and for antifungal activity against five fungal strains. Distinct antiangiogenic and antifungal activity profiles of the trans- stereoisomers, especially 1e and 1f, suggest different molecular mechanisms underlying the anti-angiogenic and anti-fungal activities of itraconazole.     

Isolation of endophytic fungi with anti-inflammatory effect in vitro from Zanthoxylum armatum

Endophytic fungus is a rich source of bioactive metabolites with multiple activities. In the present study, eight endophytic fungal strains (Z-1 to Z-8) from Zanthoxylum armatum DC. were isolated and identified, and the anti-inflammatory effect of their extracts was evaluated in vitro. The results showed that four endophytic fungal extracts (Fusarium oxysporum Schlecht. (Z-1), Alternaria arborescens E.G Simmons (Z-3), Mucor fragilis Bainier (Z-4) and Aspergillus terreus Thom (Z-6)) displayed good activities in inhibition of excessive production of nitric oxide in lipopolysaccharide-activated mouse macrophage RAW264.7 cells. Among them, the extracts of Fusarium oxysporum Schlecht showed the maximum inhibition activity with a half maximal inhibitory concentration of 174.0 μg/mL. The underlying mechanism of the anti-inflammatory effect of Fusarium oxysporum Schlecht extract was associated with its inhibition on the release of several inflammatory factors. The mRNA expression of interleukin 1β, interleukin 6, inducible nitric oxide synthase in lipopolysaccharide-activated mouse macrophage RAW264.7 cells were all inhibited by Z-1 extract detected by real-time polymerase chain reaction. In summary, several endophytic fungal from Zanthoxylum armatum have good anti-inflammatory activity and Fusarium oxysporum Schlecht possesses a promising potential to be developed to a novel anti-inflammatory agent.     

Chemical Composition and Antimicrobial Activity of the Volatile Oil of Artemisia khorassanica. from Iran

Abstract

Artemisia khorassanica. Podl. (Asteraceae) is a common perennial herb growing wild in northeastern parts of Iran. The essential oil of A. khorasanica. was isolated by hydrodistillation in 1.25 (v/w) yield. The chemical composition of the essential oil was examined by gas chromatography and gas chromatography-mass spectrometry. Thirty-one compounds were identified, representing 79.6% of the total oil. The major constituents were 1,8-cineol (17.7%), camphor (13.9%), davanone (12.2%), and isogeraniol (5.7%). Minimum inhibitory concentration was determined using agar dilution method against eight bacteria and two fungal strains. The essential oil indicated a moderate antimicrobial activity.     

Identification of important structural features of thiazolo[4,5-d]pyrimidines required for potent antifungal activity

Pyrimidines, either mononuclear or condensed with other heterocycles have established its importance in medicinal chemistry. Variety of biological activities have been reported by thiazolo[4,5-d]pyrimidine derivatives. The present work describes the synthesis and antifungal activity of several 3-(substituted)-5-(substituted)phenylamino-6-(substituted)phenylthiazolo[4,5-d]pyrimidine-7(6H)-one-2(3H)-thiones. The target compounds were synthesized by cyclocondensation of 4-amino-5-carbethoxy-3-(substituted)thiazolo-2(3H)-thione and S-methyl di(substituted)phenylisothiourea. All synthesized compounds were tested for minimum inhibitory concentration against different fungal strains such as, Aspergillus niger, A. clavatus and Candida albicans and compared with fluconazole and nystatin as reference drug. Some of the compounds have exhibited potent inhibitory activity on all fungal strains, and were found more potent than reference standard. Some of the important structural features required for broad spectrum activity in this series have been derived.     

Patent Evaluation: Novel Nonphosphorus Containing Squalene Synthetase Inhibitors as Antihypercholesterolaemic Agents

Summary

Novelty: Nonphosphorus containing compounds are disclosed as squalene synthetase inhibitors.

Biology: The compounds are proposed for the treatment of arteriosclerosis, hyperlipidaemia and also fungal infections. The intrinsic squalene synthetase inhibitory activity is measured in a standard in vitro protocol using male Charles Rivers CD rats. Data are presented in tables.

Chemistry: The novel nonphosphorus containing compounds are prepared by aerobic fermentation of Sporormiella intermedia, a bitunicate ascomycete or other organisms of the same genera.     

Antibacterial and antifungal activities of extracts of combretum molle

OBJECTIVE: In traditional medical practices of Ethiopia the aqueous extracts obtained from the stem bark of Combretum molle (R. Br. Ex. G. Don.) Engl & Diels (Combretaceae) have a longstanding reputation for the treatment of liver diseases malaria and tuberculosis. Owing to the widespread traditional uses of this plant, the studyinvestigated the antimicrobial activity the bark extract of this plant against Gram positive and and Gram negative bacteria. METHODS: Petroleum ether, dichloromethane and acetone fractions of the bark of the plant were prepared by soxhlet extraction and screened for their antimicrobial activity. The acetone fraction exhibited a powerful activity and was therefore further tested against twenty-one bacterial and six fungal strains. The minimum inhibitory concentration (MIC) of this extract was determined by checker board technique using nutrient agar medium. The zones of inhibition produced by the extract against bacteria and fungi were determined and compared by disc diffusion technique with those of pure ciprofloxacin and griseofulvin, respectively. RESULTS: The highest antibacterial action of the acetone extract was against the Gram negative organisms EscherIchia coli and Shigella spp with an MIC value of 50 mg/ml. The activity of the extract against these bacteria was comparable to that of ciprofloxacin when assessed by the disc diffusion technique. Among the fungal strains tested Candida albicans showed high susceptibility to the extract and growth was completely inhibited at a concentration of 400 microg/ml. At the same concentration, the acetone extract and the standard antifungal drug griseofulvin produced comparable zones of inhibition on C. albicans. Studies on the mode of action of the extract indicated that it was bactericidal and fungicidal. The antimicrobial activity of the extract was attributed to the high amount of hydrolysable tannins present in the bark of the plant. CONCLUSION: The acetone extract of the stem bark of C. molle has the potential for use as a natural antimicrobial agent. Further in vivo antimicrobial, phytochemical and toxicological studies are requireed to evaluate the chemotherapeutic effect of the plant.     

Antifungal Properties of Some Components of Senna Alata Flower

Antifungal activity of some components of Senna alata flower was examined against five fungi. The methanolic crude extract and the partially purified fractions were both active against standard strains of Aspergillus niger, Geotricum candidum, and Candida utilis, and local isolates of Aspergillus brevipes and Penicillium species, but at different concentrations. The minimum inhibitory concentration of the methanolic crude extract was low for all the fungal strains except Aspergillus niger with 5.0 mg/mL concentration, while the minimum inhibitory concentration of partially purified components (C and F) ranged between 0.312 mg/mL for extract F against Penicillium species and 2.5 mg/mL for extract C against Aspergillus niger, Penicillium species and Candida utilis. The minimum fungicidal concentration of the crude methanolic extract was generally higher than 5 mg/mL for most of the fungi but the partially purified extract exhibited fungicidal concentrations ranging from 2.5 mg/mL to 5.0 mg/mL. Antifungal properties against mycelial growth was also demonstrated by all the extracts against the tested strains, with the crude methanolic extract losing its activity after 48 hours. The partially purified Senna alata extracts exhibited a relatively high antifungal activity against mycelial growth with total suppression of sporulation for four days at a concentration of 2 mg/mL, while preventing fungal growth after the seventh day.     

BE-31405, a new antifungal antibiotic produced by Penicillium minioluteum. I. Description of producing organism, fermentation, isolation, physico-chemical and biological properties

A new antifungal antibiotic, BE-31405, was isolated from the culture broth of a fungal strain, Penicillium minioluteum F31405. BE-31405 was isolated by adsorption on high porous polymer resin (Diaion HP-20), followed by solvent extraction, precipitation and crystallization. BE-31405 showed potent growth inhibitory activity against pathogenic fungal strains such as Candida albicans, Candida glabrata and Cryptococcus neoformans, but did not show cytotoxic activity against mammalian cells such as P388 mouse leukemia. The mechanism studies indicated that BE-31405 inhibited the protein synthesis of C. albicans but not of mammalian cells.     

Quinolactacins A, B and C: novel quinolone compounds from Penicillium sp. EPF-6. I. Taxonomy, production, isolation and biological properties

Quinolactacins A (1), B (2) and C (3), novel quinolone antibiotics have been found from the cultured broth of a fungal strain isolated from the larvae of the mulberry pyralid Margaronia pyloalis Welker). The fungal strain, EPF-6 was identified as Penicillium sp. from its morphological characteristics. Quinolactacins were obtained from the culture medium by solvent extraction and chromatographic purification. Compound 1 showed inhibitory activity against tumor necrosis factor (TNF) production induced by murine peritoneal macrophages and macrophage-like J774.1 cells stimulated with lipopolysaccharide (LPS).     

An in vitro study of the efficacy of rifampicin and minocycline coated umbilical venous catheters

The use of antibiotic coated catheters has been proposed as a means of reducing catheter related sepsis. In this study, an in vitro comparison of bacterial colonisation rates was made between uncoated umbilical venous catheters and catheters coated with rifampicin and minocycline. The following parameters were determined; the direct antimicrobial effect of coated and uncoated catheter segments against a range of organisms associated with line sepsis, the assessment of the decline in antimicrobial activity in coated catheters immersed in plasma and the inhibitory efficacy of the catheters to colonisation over a 28-day period. Minocycline and rifampicin coated umbilical catheters showed a superior inhibitory effect and prevented colonisation with the commoner line-related organisms, when compared with uncoated catheters. The inhibitory effect declined after 14 days in the human plasma. Resistance to colonisation in vitro may not extend beyond 21 days.     

An evaluation of the antifungal effect of bifonazole on Torulopsis glabrata and Candida albicans under various in vitro test conditions

1-[(4-Biphenylyl)-phenylmethyl]-1H-imidazole (bifonazole, Bay h 4502, Mycospor) showed in vitro significant inhibitory activity against Torulopsis glabrata, Candida albicans, Pityrosporum ovale, Corynebacterium acnes and Staphylococcus epidermidis. The antifungal activity of bifonazole against T. glabrata and C. albicans varied with the in vitro test conditions. There was a tendency for minimal inhibitory concentrations to increase as fungal inoculum size was increased and as incubation time was prolonged. For T. glabrata, but not for C. albicans, minimal inhibitory concentrations were lower in liquid than on solid culture media. The antifungal activity was less pronounced at low pH values. Because of these variations laboratory tests for the in vitro determination of antifungal sensitivities should be carried out under standardized test conditions such as small inocula, a limited incubation period and appropriate culture media. The solubility of bifonazole in aqueous solution is very low. In addition, more bifonazole dissolves at low than at high pH values.