In vivo synergism of free miltefosine or in alginate-based nanocarrier combined with voriconazole on aspergillosis.

Aim: To evaluate the activity of miltefosine (MFS), in its free form or loaded-alginate nanoparticles (MFS-AN), alone or combined with voriconazole (VRC) on Aspergillus fumigatus and Aspergillus flavus. Materials & methods: A broth microdilution assay was used for the susceptibility testing of Aspergillus isolates, and the antifungal efficacy was assessed using the aspergillosis model in Galleria mellonella larvae. Results: The in vitro synergistic effect of MFS with VRC was observed only against A. fumigatus, whereas both combined therapies (MFS + VRC and MFS-AN + VRC) showed synergism in reducing the larval mortality rate and fungal burden in the larvae infected by A. fumigatus and A. flavus. Conclusions: MFS and MFS-AN combined with VRC may be an important strategy for improving antifungal therapy against aspergillosis.

Effect of the essential oils of Satureja montana L., Myristica fragrans H. and Cymbopogon flexuosus S. on mycotoxin-producing Aspergillus flavus and Aspergillus ochraceus antifungal properties of essential oils.

Essential oils can be a useful alternative to the use of synthetic fungicides because they have biological potential and are relatively safe for food and agricultural products. The objectives of the present study were to evaluate the antifungal and antimycotoxigenic activities of the essential oils from Satureja montana L., Myristica fragrans H. and Cymbopogon flexuosus S. against Aspergillus flavus and Aspergillus ochraceus, as well as their effects on ergosterol synthesis and membrane morphology. The antifungal potential was evaluated by mycelial growth analysis and scanning electron microscopy. Fungicidal effects against A. flavus, with MFC of 0.98, 15.62 and 0.98 µL/mL, respectively, were observed for the essential oils from S. montana, M. fragrans and C. flexuosus. Aspergillus ochraceus did not grow in the presence of concentrations of 3.91, 15.62 and 0.98 µL/mL of the essential oils from S. montana, M. fragrans and C. flexuosus, respectively. The essential oils significantly inhibited the production of ochratoxin A by the fungus A. ochraceus. The essential oils also inhibited the production of aflatoxin B1 and aflatoxin B2. The biosynthesis of ergosterol was inhibited by the applied treatments. Biological activity in the fungal cell membrane was observed in the presence of essential oils, given that deleterious effects on the morphologies of the fungi were detected. The essential oils under study are promising as food preservatives because they significantly inhibit toxigenic fungi that contaminate food. In addition, the essential oils hindered the biosynthesis of mycotoxins.

Impact of encapsulated orange essential oil with ß-cyclodextrin on technological, digestibility, sensory properties of wheat cakes as well as Aspergillus flavus spoilage.

BACKGROUND: The majority of studies with essential oils in foods focus mainly on improving the shelf life of products; however, the present study goes further and demonstrates not only the effect of essential oil on conservation properties, but also the effect of free and encapsulated orange essential oil (OEO) on the technological, sensorial and digestibility properties of bakery products. RESULTS: OEO was encapsulated into ß-cyclodextrin (ß-CD) by inclusion complex formation (ß-CD/OEO 97.4% of encapsulation efficiency). OEO demonstrated in vitro antifungal activity against Aspergillus flavus (inhibition zone of 11.33 mm on mycelial growth). In situ antifungal activity against A. flavus confirmed that free OEO can effectively delay the fungal growth, unlike encapsulated OEO. Regarding texture profile and starch digestibility: cake with ß-CD/OEO showed lower hardness (31.64 N) and lower starch digestibility (69.10%) than cake with free OEO (44.30 N; 82.10%, respectively) and the addition of OEO (both free and encapsulated) decreased the adhesiveness of the cakes. Cake with free OEO showed a higher intensity of orange aroma, being preferred by 60% of panelists, whereas cake with ß-CD/OEO presented a very slight orange taste and aroma. CONCLUSION: The encapsulation of OEO into ß-CD improved the crumb texture of cakes and promoted a lower starch digestibility in the cakes. On the other hand, the encapsulation process was not effective under the conditions tested (OEO concentration and baking temperatures), compromising the action of the OEO as a natural flavoring and preservative agent. © 2021 Society of Chemical Industry.

Synthetic antimicrobial agents inhibit aflatoxin production.

Antimicrobial peptides (AMPs) are biologically active molecules that can eradicate bacteria by destroying the bacterial membrane structure, causing the bacteria to rupture. However, little is known about the extent and effect of AMPs on filamentous fungi. In this study, we synthesized small molecular polypeptides by an inexpensive heat conjugation approach and examined their effects on the growth of Aspergillus flavus and its secondary metabolism. The antimicrobial agents significantly inhibited aflatoxin production, conidiation, and sclerotia formation in A. flavus. Furthermore, we found that the expression of aflatoxin structural genes was significantly inhibited, and the intracellular reactive oxygen species (ROS) level was reduced. Additionally, the antimicrobial agents can change membrane permeability. Overall, our results demonstrated that antimicrobial agents, safe to mammalian cells, have an obvious impact on aflatoxin production, which indicated that antimicrobial agents may be adopted as a new generation of potential agents for controlling aflatoxin contamination.

Effects of chlorpyrifos on growth and aflatoxin B1 production by Aspergillus section Flavi strains on maize-based medium and maize grains.

Chlorpyrifos is one of the most used insecticides in agro-ecosystems and is repeatedly applied due to the increase in pest resistance, which leads to environmental accumulation. The aim of this work was to evaluate the effect of chlorpyrifos on growth and aflatoxin B1 (AFB1) production by four Aspergillus section Flavi strains, under different water conditions-aW (0.93, 0.95 and 0.98)-on maize-based medium (MMEA) and maize grains supplied with 0.06 to 1.4 mmol/L of chlorpyrifos. MMEA plates were incubated at 18, 28, and 37 °C and plates with maize grains at 25 °C during 21 days. Chlorpyrifos stimulated the growth and AFB1 production of non-target organisms, such as Aspergillus section Flavi strains, both at low (0.06 mmol/L) and at high concentrations (1.4 mmol/L) on MMEA and maize grains. Stimulation occurred over a wide range of temperature and aw conditions. The toxin concentration produced by the two strains on MMEA at 18 °C increased when the concentration of chlorpyrifos also increased, being most significant at 0.6 mmol/L. In conclusion, the presence of chlorpyrifos should be considered as a factor, together with environmental conditions, for the development of effective production practices of maize grains, in order to avoid fungal growth and AFB1 production, to prevent both economic losses and risks to human and animal health.

Cellular, physiological and molecular approaches to investigate the antifungal and anti-aflatoxigenic effects of thyme essential oil on Aspergillus flavus.

Several approaches, including the detection of apoptotic-like cell death, aflatoxin B1 (AFB1) production and gene expression analysis, were carried out to provide insights into the antifungal and anti-aflatoxigenic effects of thyme essential oil (EO) on Aspergillus flavus. At 0.5 µL mL-1, thyme EO completely inhibited A. flavus growth. Furthermore, this antifungal activity triggered significant apoptosis, via nuclear condensation (87.5% of nuclei analyzed) and plasma membrane damage (in 100% of treated hyphae). Further analysis of AFB1 production and gene expression related to secondary metabolism (laeA) and the mechanism of virulence (lipA and meT) of A. flavus in the presence of thyme EO indicated important physiological changes related to its anti-aflatoxigenic property. These results highlight the potent antifungal abilities of thyme EO in controlling A. flavus and AFB1 production, especially the abilities that operate by exerting changes at the molecular level and inducing significant apoptotic-like cell death.

Antifungal and antiaflatoxigenic activity of rosemary essential oil (Rosmarinus officinalis L.) against Aspergillus flavus.

The increased risk to health by diverse pathologies, such as cancer, liver diseases, and endocrine alterations, caused by chemical residues in food, has led to the search for sustainable agricultural management alternatives, such as the use of essential oils for the development of natural and eco-friendly fungicides. The aim of this study was to evaluate the antifungal and antiaflatoxigenic activity of Rosmarinus officinalis L. essential oil (REO) against Aspergillus flavus Link. REO was obtained by hydrodistillation and its major components were identified as 1,8-cineole (eucalyptol, 52.2%), camphor (15.2%) and α-pinene (12.4%) by GC/MS and NMR. The minimum inhibitory concentration (MIC) and minimum fungicidal concentration (MFC) were both 500 µg/mL. REO reduced the mycelial growth of A. flavus at a concentration of 250 µg/mL (15.3%). The results obtained from scanning electron microscopy (SEM) demonstrated a reduction in the size of conidiophores and in the thickness of hyphae in A. flavus caused by treatment with REO (250 µg/mL). The production of ergosterol and the biomass of mycelium were both reduced as the REO treatment concentration increased. The production of aflatoxins B1 and B2 was inhibited after treatment with 250 µg/mL REO, a concentration below the MIC/MFC, indicating that the antiaflatoxigenic effect of REO is independent of its antifungal effect and is likely due to its direct action upon toxin biosynthesis. The data demonstrated that REO may be used as an alternative to synthetic fungicides.

Change in the clinical antifungal sensitivity profile of Aspergillus flavus induced by azole and a benzimidazole fungicide exposure.

The study evaluated the change in the clinical antifungal sensitivity profile of A. flavus strains after exposure to azole and benzimidazole fungicide. Exposure to fungicide altered the sensitivity profile for the antifungal itraconazole, voriconazole and posaconazole. This change was characterized by an increase in the minimum inhibitory concentration (MIC) from 16 to 32 times, evidencing the development of resistance phenotypes. The most significant changes were found after exposure to a pool of the fungicide with MIC of up to 256 times, which is considered, to the best of our knowledge, the first case report of such a high level of resistance induced by azole fungicide exposure. This observation probably indicates a synergistic action among azole compounds that potentiates the development of resistance phenotypes. In addition, exposure to fungicide changed the pigmentation of the colonies from green to white. The development of resistance to fungicides represents risks to human health, since azole fungicides are used widely in the agriculture, and a single agricultural fungicide spray often includes more than one azole compound.

Antibacterial and Antifungal Activities of Compounds Isolated from Gymnosporia Royleana (Celastraceae) / Actividades antibacterianas y antifúngicas de compuestos aislados de Gymnosporia Royleana (Celastraceae)

ABSTRACT Objective: In the present study, five new source compounds isolated from aerial parts of Gymnosporia royleana (G royleana) were screened for antibacterial and antifungal activities. Methods: Extraction from plant material was carried out using cold maceration technique. Isolation of pure compounds was accomplished through repeated column chromatography of different fractions obtained from crude extract and using silica gel as stationary phase. Their structures were established via advanced spectroscopic techniques along with the spectral data previously reported for these compounds. Dilution method was used for the evaluation of antimicrobial potential of the compounds against various microbial strains. Results: Among the tested compounds, Gymnosporin B displayed moderate antimicrobial activity against Escherichia Coli (E coli), Staphylococcus aureus (S aureus), Candida albicans (C albicans) and Aspergillus flavus (A flavus) [minimum inhibitory concentration (MIC) range; 32-64 μg/mL]. Similarly, Gymnosporin C also showed moderate activity against E coli and S aureus (MIC; 32 μg/mL each) as well as weak activity against C albicans and A flavus (MIC; 64 μg/mL each). However, Royaflavone showed moderate antibacterial activity against S aureus only (MIC; 32 μg/mL). Antimicrobial activity of the rest of the compounds was weak and negligible. Conclusion: The present study has provided fascinating results of antimicrobial activities of the isolated compounds. However, the broad antimicrobial spectrum of Gymnosporin B and Gymnosporin C demands for further exploration of these triterpenes, both on the basis of mechanism and quantitative structure-activity relationship.

RESUMEN Objetivo: En el presente estudio, cinco nuevos compuestos de origen aislados de partes aéreas de Gymnosporia royleana (G royleana) fueron tamizados en sus actividades antibacterianas y antifúngicas. Métodos: La extracción de material vegetal se realizó mediante la técnica de maceración en frío. El aislamiento de compuestos puros se logró a través de la cromatografía en columna repetida de diversas fracciones obtenidas del extracto crudo y usando gel de silicona como fase estacionaria. Sus estructuras fueron establecidas mediante técnicas espectroscópicas avanzadas junto con los datos espectrales previamente reportados para estos compuestos. El método de dilución fue usado para evaluar el potencial antimicrobiano de los compuestos contra diversas cepas microbianas. Resultados: Entre los compuestos sometidos a prueba, Gymnosporina B mostró una actividad antimicrobiana moderada contra Escherichia Coli (E coli), Staphylococcus aureus (S aureus), Candida Albicans (C albicans) y Aspergillus flavus (A flavus) [rango de concentración inhibitoria mínima (CIM); 32 - 64 μg/mL]. De manera similar, Gymnosporina C también mostró actividad moderada contra E coli y S aureus (CIM; 32 μg/mL cada uno) así como débil actividad frente a C albicans y A flavus (CIM; 64 μg/mL cada uno). Sin embargo, Royaflavone mostró actividad antibacteriana moderada sólo frente a S aureus (CIM; 32 μg/mL). La actividad antimicrobiana del resto de los compuestos fue débil e insignificante. Conclusión: El presente estudio ha proporcionado resultados interesantes acerca de las actividades antimicrobianas de los compuestos aislados. Sin embargo, el amplio espectro antimicrobiano de la Gymnosporina B y la Gymnosporina C exige una mayor exploración de estos triterpenos, tanto sobre la base del mecanismo como a partir de la relación cuantitativa estructura-actividad.

Effect of atrazine on growth and production of AFB1 in Aspergillus section Flavi strains isolated from maize soils.

Atrazine is one of the most frequently used herbicides in Argentina for controlling broadleaf weeds and annual grasses. Currently, there is limited information on the impact of triazine herbicides on mycotoxin production and growth parameters of toxigenic fungi in maize. The objective of this study was to evaluate the effect of different concentrations of atrazine on the lag phase prior to growth, the growth rate, and on production of aflatoxin B1 (AFB1) of Aspergillus flavus and Aspergillus parasiticus strains, on maize meal extract agar (MMEA) under different water activities (aW) and temperatures. A commercial formulation of atrazine was added to MMEA medium at 0, 5, 10, 50, or 100 mmol/l, adjusted to 0.98, 0.95, and 0.93 aW, and incubated at 28 °C and 37 °C for 21 days. AFB1 was determined by HPLC after 7, 14, and 21 days of incubation. In the control treatments, a significant increase in the time prior to growth was observed and as the aW decreased, at both temperatures, the growth rate of the strains also decreased. A significant increase in growth rate was observed as the concentration of atrazine in the medium increased, for all aW levels tested. The optimal conditions for the accumulation of AFB1 in the control treatments were 0.98 aW and 28 °C, after 7 days of incubation. As the concentration of herbicide increased, AFB1 production also increased (P < 0.05). These results add to the knowledge about consequences with regard to aflatoxin production of the use of excessive atrazine doses in extensive maize culture.

Development and removal ability of non-toxigenic Aspergillus section Flavi in presence of atrazine, chlorpyrifos and endosulfan.

This study evaluated the in vitro effect of three concentrations of atrazine, chlorpyrifos and endosulfan on the growth parameters of four non-toxigenic Aspergillus section Flavi strains. The ability of the strains to remove these pesticides in a synthetic medium was also determined. Growth parameters were measured on soil extract solid medium supplied with 5, 10 and 20mg/l of each pesticide, and conditioned to -0.70, -2.78, -7.06 and -10.0 water potential (MPa). Removal assays were performed in Czapek Doc medium (CZD) supplied with 20mg/l of each pesticide under optimal environmental conditions (-2.78 of MPa and 25°C). The residual levels of each pesticide were detected by the reversed-phase HPLC/fluorescence detection system. The lag phases of the strains significantly decreased in the presence of the pesticides with respect to the control media. This result indicates a fast adaptation to the conditions assayed. Similarly, the mycelial growth rates in the different treatments increased depending on pesticide concentrations. Aspergillus oryzae AM 1 and AM 2 strains showed high percentages of atrazine degradation (above 90%), followed by endosulfan (56 and 76%) and chlorpyrifos (50 and 73%) after 30 days of incubation. A significant (p<0.001) correlation (r=0.974) between removal percentages and growth rate was found. This study shows that non-toxigenic Aspergillus section Flavi strains from agricultural soils are able to effectively grow in the presence of high concentrations of atrazine, chlorpyrifos and endosulfan under a wide range of MPa conditions. Moreover, these strains have the ability to remove high levels of these pesticides in vitro in a short time.

Antifungal activity of silver nanoparticles and simvastatin against toxigenic species of Aspergillus.

Aspergillus spp. are ubiquitous fungi that grow on stored grains. Some species produce toxins that can harm human and animal health, leading to hepato- and nephrotoxicity, immunosuppression and carcinogenicity. Major fungicides used to prevent fungal growth may be toxic to humans and their repeated use over time increases levels of resistance by microorganisms. Nanotechnology is an emerging field that allows use of antimicrobial compounds in a more efficient manner. In this study, was evaluated the antifungal activity of biogenic silver nanoparticles (AgNPs, synthesized by fungi) and simvastatin (SIM, a semi-synthetic drug), alone and in combination against three toxigenic species belonging to the genera Aspergillus section Flavi (Aspergillus flavus, Aspergillus nomius and Aspergillus. parasiticus) and two of section Circumdati (Aspergillus ochraceus and Aspergillus melleus). SIM exhibited a MIC50 of 78 µg/mL against species of Section Flavi and a MIC50 of 19.5 µg/mL against species of Section Circumdati. The MIC50 of AgNPs against Aspergillus flavus, Aspergillus nomius and Aspergillus parasiticus was 8 µg/mL, while the MIC50 was 4 µg/mL against Aspergillus melleus and Aspergillus ochraceus. Checkerboard assay showed that these compounds, used alone and in combination, have synergistic and additive effects against toxicogenic species of Aspergillus. Analysis by SEM gives an idea of the effect of SIM and AgNPs alone and in combination on spore germination and vegetative growth. Ultrastructural analysis revealed that spore germination was prevented, or aberrant hyphae were formed with multilateral branches upon treatment with SIM and AgNPs. These results reveal potential benefits of using combination of AgNPs and SIM to control fungal growth.

Pyranopyrazoles as efficient antimicrobial agents: Green, one pot and multicomponent approach.

Innovative therapeutic heterocycles having precisely thiadiazolyl-pyranopyrazole fragments were prepared by using the ecofriendly synthetic route. Entire compounds formed in quantitative yields. All the composites tested for their antimicrobial effectiveness against four microbial, two beneficial fungi's and accurately measured the minimum inhibitory concentrations (MIC and MBC/MFC), along with some initial structure activity relationships (SARs) also discussed. From the biological outcomes, the motif 6f provided an outstanding activity against all six pathogens. The possible presence of a nitro substituent on this composite may undoubtedly enhance the activity. In addition, amalgams 6d, 6g and 6l displayed promising antimicrobial results. This may be justified to the presence of electron capture group attached to the benzene ring, while the combinations 6j and 6k were zero effect towards all bacterial strains. The other compounds were excellent to low antimicrobial efficiency. The intriguing point was observed that all the active compounds had in common immense antibacterial effectiveness on Gram-negative bacteria than Gram-positive one and more antifungal activity on A. niger compare to other fungus. All things considered and suggested that this outstanding green synthetic approach is used to develop biological active compounds. On top of that, biological results confirmed that these biologically energetic motifs suitable for additional preclinical examine with the aim of standing novel innovative drugs.

Mycelial Growth and Antimicrobial Activity of Pleurotus Species (Agaricomycetes).

The objective of this study was to analyze mycelial growth under different culture conditions and antimicrobial activity of Pleurotus ostreatus (Jacq.: Fr.) Kumm. (DPUA 1533) and P. ostreatus (Jacq.: Fr.) Kumm. cv. Florida (DPUA 1534) against fungi and bacteria of medical importance. The growth of Pleurotus species was evaluated in natural and complex media, with and without light, at 25°C and 28°C for 8, 15, and 30 days. Candida albicans (DPUA 1336), Cryptococcus laurentii (DPUA 1501), Aspergillus flavus (DPUA 1836), Escherichia coli (DAUPE 224), and Mycobacterium smegmatis (ATCC 607) were used to test antibiosis. Under all growth conditions in vitro, Pleurotus species evidenced growth and high density of mycelia on potato dextrose agar and Sabouraud agar with yeast extract; mycelial growth but lesser mycelial density was observed on rice bran extract agar. Organic mycelial extracts of Pleurotus species exhibited potential antibacterial and antifungal activity, and were selective for the tested microorganisms.

In vitro interactions of azoles and echinocandins against clinical strains of Aspergillus flavus.

Combinations of an azole (itraconazole, voriconazole, or posaconazole) with an echinocandin (caspofungin, micafungin, or anidulafungin) were tested against 20 clinical isolates of Aspergillus flavus according to EUCAST guidelines. The interactions were determined using two endpoints-minimal effective concentration (MEC) and minimal inhibitory concentration (MIC)-via calculation of the fractional inhibitory concentration (FIC) index. A higher prevalence of synergistic interactions was observed for MIC, whereas indifference was the most frequent outcome according to MEC among the 20 strains. Combined treatment of A. flavus with these two important classes of antifungals should be explored further in in vivo studies.

In vitro antifungal susceptibility of clinical and environmental isolates of Aspergillus fumigatus and Aspergillus flavus in Brazil

ABSTRACT The in vitro susceptibility of 105 clinical and environmental strains of Aspergillus fumigatus and Aspergillus flavus to antifungal drugs, such as amphotericin B, azoles, and echinocandins was evaluated by the broth microdilution method proposed by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Following the EUCAST-proposed breakpoints, 20% and 25% of the clinical and environmental isolates of A. fumigatus, respectively, were found to be resistant to itraconazole (Minimal Inhibitory Concentration, MIC > 2.0 mg/L). Voriconazole showed good activity against A. fumigatus and A. flavus strains, except for one clinical strain of A. fumigatus whose MIC was 4.0 mg/L. Posaconazole (≤0.25 mg/L) also showed appreciable activity against both species of Aspergillus, except for six A. fumigatus strains with relatively higher MICs (0.5 mg/L). The MICs for Amphotericin B ranged from 0.06 to 1.0 mg/L for A. fumigatus, but were much higher (0.5-8.0 mg/L) for A. flavus. Among the echinocandins, caspofungin showed a geometric mean of 0.078 and 0.113 against the clinical and environmental strains of A. flavus, respectively, but had elevated minimal effective concentrations (MECs) for seven of the A. fumigatus strains. Anidulafungin and micafungin exhibited considerable activity against both A. fumigatus and A. flavus isolates, except for one environmental isolate of A. fumigatus that showed an MEC of 1 mg/L to micafungin. Our study proposes that a detailed investigation of the antifungal susceptibility of the genus Aspergillus from different regions of Brazil is necessary for establishing a response profile against the different classes of antifungal agents used in the treatment of aspergillosis.

In vitro antifungal susceptibility of clinical and environmental isolates of Aspergillus fumigatus and Aspergillus flavus in Brazil.

The in vitro susceptibility of 105 clinical and environmental strains of Aspergillus fumigatus and Aspergillus flavus to antifungal drugs, such as amphotericin B, azoles, and echinocandins was evaluated by the broth microdilution method proposed by the European Committee on Antimicrobial Susceptibility Testing (EUCAST). Following the EUCAST-proposed breakpoints, 20% and 25% of the clinical and environmental isolates of A. fumigatus, respectively, were found to be resistant to itraconazole (Minimal Inhibitory Concentration, MIC>2.0mg/L). Voriconazole showed good activity against A. fumigatus and A. flavus strains, except for one clinical strain of A. fumigatus whose MIC was 4.0mg/L. Posaconazole (≤0.25mg/L) also showed appreciable activity against both species of Aspergillus, except for six A. fumigatus strains with relatively higher MICs (0.5mg/L). The MICs for Amphotericin B ranged from 0.06 to 1.0mg/L for A. fumigatus, but were much higher (0.5-8.0mg/L) for A. flavus. Among the echinocandins, caspofungin showed a geometric mean of 0.078 and 0.113 against the clinical and environmental strains of A. flavus, respectively, but had elevated minimal effective concentrations (MECs) for seven of the A. fumigatus strains. Anidulafungin and micafungin exhibited considerable activity against both A. fumigatus and A. flavus isolates, except for one environmental isolate of A. fumigatus that showed an MEC of 1mg/L to micafungin. Our study proposes that a detailed investigation of the antifungal susceptibility of the genus Aspergillus from different regions of Brazil is necessary for establishing a response profile against the different classes of antifungal agents used in the treatment of aspergillosis.

Pharmacodynamics of the Novel Antifungal Agent F901318 for Acute Sinopulmonary Aspergillosis Caused by Aspergillus flavus.

Background: Aspergillus flavus is one of the most common agents of invasive aspergillosis and is associated with high mortality. The orotomides are a new class of antifungal agents with a novel mechanism of action. An understanding of the pharmacodynamics (PD) of the lead compound F901318 is required to plan safe and effective regimens for clinical use. Methods: The pharmacokinetics (PK) and PD of F901318 were evaluated by developing new in vitro and in vivo models of invasive fungal sinusitis. Galactomannan was used as a pharmacodynamic endpoint in all models. Mathematical PK-PD models were used to describe dose-exposure-response relationships. Results: F901318 minimum inhibitory concentrations (MICs) ranged from 0.015 to 0.06 mg/L. F901318 induced a concentration-dependent decline in galactomannan. In the in vitro model, a minimum concentration:MIC of 10 resulted in suppression of galactomannan; however, values of approximately 10 and 9-19 when assessed by survival of mice or the decline in galactomannan, respectively, were equivalent or exceeded the effect induced by posaconazole. There was histological clearance of lung tissue that was consistent with the effects of F901318 on galactomannan. Conclusions: F901318 is a potential new agent for the treatment of invasive infections caused by A flavus with PDs that are comparable with other first-line triazole agents.

Synthesis, characterization and biological studies of a cobalt(III) complex of sulfathiazole.

The emergence of old and new antibiotic resistance created in the last decades revealed a substantial medical need for new classes of antimicrobial agents. The antimicrobial activity of sulfa drugs is often enhanced by complexation with metal ions, which is in concordance with the well-known importance of metal ions in biological systems. Besides, sulfonamides and its derivatives constitute an important class of drugs, with several types of pharmacological agents possessing antibacterial, anti-carbonic anhydrase, diuretic, hypoglycemic, antithyroid, antiviral and anticancer activities, among others. The purpose of this work has been the obtainment, characterization and determination of biological properties (antibacterial, antifungal, mutagenicity and phytotoxicity) of a new Co(III)-sulfathiazole complex: Costz, besides of its interaction with bovine serum albumin (BSA). The reaction between sodium sulfathiazole (Nastz) and cobalt(II) chloride in the presence of H2O2 leads to a brown solid, [CoIII(stz)2OH(H2O)3], (Costz). The structure of this compound has been examined by means of elemental analyses, FT-IR, 1H NMR, UV-Visible spectrometric methods and thermal studies. The Co(III) ion, which exhibits a distorted octahedral environment, could coordinate with the N thiazolic atom of sulfathiazolate. The complex quenched partially the native fluorescence of bovine serum albumin (BSA), suggesting a specific interaction with the protein. The Costz complex showed, in vitro, a moderate antifungal activity against Aspergillus fumigatus and A. flavus. As antibacterial, Costz displayed, in vitro, enhanced activity respective to the ligand against Pseudomonas aeruginosa. Costz did not show mutagenic properties with the Ames test. In the Allium cepa test the complex showed cytotoxic properties but not genotoxic ones. These results may be auspicious, however, further biological studies are needed to consider the complex Costz as a possible drug in the future.

The use of chitosan in protecting wooden artifacts from damage by mold fungi

Background: Many buildings in Egypt e.g. museums, mosques and churches, do not possess controlled environments for minimizing the risks of damage of wooden artifacts due to the growth of fungi. Fungal damage usually appears as change in wood color, appearance of stains, and sometimes deformation of wooden surfaces. In this study we focused on the effect that some fungi exert on the properties of wooden artifacts and evaluated the effectiveness of different concentrations of chitosan on their protection against damage by mold fungi. Results: Samples were collected from different monuments and environments, and fungi growing on them were isolated and identified. The isolated Penicillium chrysogenum, Aspergillus flavus and /Aspergillus niger strains were used for the infestation of new pitch pine samples. The results revealed that the lightness of samples infected with any of the tested fungi decreased with increasing incubation times. XRD analysis showed that the crystallinity of incubated samples treated individually with the different concentrations of chitosan was lower than the crystallinity of infected samples. The crystallinity index measured by the first and the second method decreased after the first and second months but increased after the third and fourth months. This may due to the reducing of amorphous part by enzymes or acids produced by fungi in wooden samples. Conclusions: The growth of fungi on the treated wood samples decreased with increasing the concentration of chitosan. Hence, it was demonstrated that chitosan prevented fungal growth, and its use could be recommended for the protection of archeological wooden artifacts.