Fueling Open‐Source Drug Discovery: 177 Small‐Molecule Leads against Tuberculosis

With the aim of fuelling open‐source, translational, early‐stage drug discovery activities, the results of the recently completed antimycobacterial phenotypic screening campaign against Mycobacterium bovis BCG with hit confirmation in M. tuberculosis H37Rv were made publicly accessible. A set of 177 potent non‐cytotoxic H37Rv hits was identified and will be made available to maximize the potential impact of the compounds toward a chemical genetics/proteomics exercise, while at the same time providing a plethora of potential starting points for new synthetic lead‐generation activities. Two additional drug‐discovery‐relevant datasets are included: a) a drug‐like property analysis reflecting the latest lead‐like guidelines and b) an early lead‐generation package of the most promising hits within the clusters identified.     

Iron-enriched natural zeolite modified carbon paste electrode for H2O2 detection

This work demonstrates that iron-enriched natural zeolitic volcanic tuff (Paglisa deposit, Cluj county, Transilvania, Romania) resulting from a previous use as adsorbent in wastewater treatment can be recycled into effective electrode modifier applied to the electrocatalytic detection of hydrogen peroxide. After physico-chemical characterization of tuff samples using various techniques such as chemical analysis, X-ray diffraction, scanning electron microscopy, infrared spectroscopy, BET analysis and X-ray photoelectron spectroscopy, the electrochemical response of the iron-enriched zeolites was studied on the basis of solid carbon paste electrodes modified with these samples. The results indicate that iron centers in the zeolite are electroactive and that they act as electrocatalysts in the voltammetric and amperometric detection of H₂O₂. Best performance was achieved in phosphate buffer at pH 7, showing a sensitivity of 0.57 mA M⁻¹ cm⁻², a detection limit down to 60 μM, and a linear domain up to 100 mM H₂O₂.     

Treatment of wastewaters from the olive mill industry by sonication

BACKGROUND: In this study, the effects of additives (manganese (III) oxide (Mn₃O₄), Cu⁺², Fe⁰ and potassium iodate (KIO₃)) and radical scavengers (sodium carbonate (Na₂CO₃), perfluorohexane (C₆F₁₄) and t‐buthyl alcohol (C₄H₁₀O)) on the dephenolization, decolorization, dearomatization and detoxification of olive mill wastewater (OMW) by sonication were investigated because wastewaters from this industry are not removed effectively. RESULTS: The maximum COD, color, total phenol and total aromatic amines (TAAs) removal efficiencies were 63, 82, 78 and 71%, respectively, at 60 °C with sonication only. The TAAs and phenol yields were increased to 96 and 97% with 6 mg L^?1 KIO₃ and 3 mg L^?1 Fe⁰ while color removal reached 97% with 6 mg L^?1 C₆F_14. The total annual cost with sonication only was 665 € m^?3 year^?1 while the cost slightly increased (666€ m³ year^?1) with C₆F₁₄. The maximum acute toxicity removals were 97‐98% in Daphnia magna and Vibrio fischeri The Microtox acute toxicity test was more sensitive than the Daphnia magna to the OMW samples. CONCLUSION: COD, color, total phenol, TAAs and toxicity in an OMW were removed efficiently and cost‐effectively by sonication. © 2012 Society of Chemical Industry     

Risk assessment of staphylococcal poisoning due to consumption of informally-marketed milk and home-made yoghurt in Debre Zeit, Ethiopia

The objectives of the study were twofold: to prove that participatory risk assessment can be applied to informally-marketed foods, and to assess the risk of staphylococcal poisoning through consumption of raw milk and home-made yoghurt in Debre Zeit, Ethiopia. Rapid urban appraisals were combined with conventional interviews to identify and quantify formal and informal milk value chains and to collect information on consumers' food preparation and consumption behavior. Milk was sampled in 170 dairy farms and 5 milk collection centers and microbiological tests were conducted. Published data on milk fermentation in Ethiopia was combined with a growth model of Staphylococcus aureus to develop a stochastic risk model. The annual incidence rate of staphylococcal poisoning was estimated to be 20.0 (90% CI: 13.9-26.9) per 1000 people. When the effect of fermentation was removed from the model, the annual incidence rate increased to 315.8 (90% CI: 224.3-422.9) per 1000 people, showing the importance of traditional food preparation methods in risk mitigation; traditional milk fermentation reduced the risk by 93.7%. Improving the safety of milk and dairy products could be achieved through supporting appropriate traditional food preparation and consumption where an industrial risk mitigation system is not feasible. Participatory risk assessment was shown to be applicable to informal food value chain.     

Effect of reagent type on the acetylation of barley and maize starches

The objective of this work was to study the effect of reagent type on properties of acetylated barley starch (BS) and maize starch (MS) after modification with acetic anhydride (AA) and vinyl acetate (VA) at similar molar concentration for mole of glucose of both reagents. Degree of substitution (DS), morphological characteristics and granule size distribution, gelatinization and retrogradation, pasting properties, and X‐ray diffraction pattern were evaluated. Acetylation disturbs the short and long range order, and the effect was higher with AA than VA, and for BS than MS. This is due to the higher DS determined in AA–BS. In the pasting profile, acetylated starch showed the maximum peak viscosity at lower temperature, this effect was strongest for BS and anhydride acetic‐acetylation. Differential scanning calorimetry showed decrease in gelatinization parameters in acetylated starches (temperatures and enthalpy), and retrogradation was suppressed by acetylation. This effect was stronger in starches acetylated with AA despite their higher DS. This pattern can be explained from the occurrence of surface effects in acetylation with AA.     

Ligand-based virtual screening, parallel solution-phase and microwave-assisted synthesis as tools to identify and synthesize new inhibitors of mycobacterium tuberculosis

In an attempt to identify new inhibitors of the growth of Mycobacterium tuberculosis (MTB), the causative agent of tuberculosis, a procedure for the generation, design, and screening of a ligand-based virtual library was applied. This used both an in silico protocol centered on a recursive partitioning (RP) model described herein, and a pharmacophoric model for antitubercular agents previously generated by our research group. Two candidates emerged from databases of commercially available compounds, both characterized by a minimum inhibitory concentration (MIC) of 25 microg mL(-1). Based on these compounds, two series of derivatives were synthesized by both parallel solution-phase and microwave-assisted synthesis, leading to enhanced antimycobacterial activity. During both the design and synthesis, attention was focused on the efficient allocation of available resources with the aim of reducing the overall costs associated with calculation and synthesis.     

Assembly of ligand-stripped nanocrystals into precisely controlled mesoporous architectures

The properties of mesoporous materials hinge on control of their composition, pore dimensions, wall thickness, and the size and shape of the crystallite building units. We create ordered mesoporous materials in which all of these parameters are independently controlled. Different sizes (from 4.5 to 8 nm) and shapes (spheres and rods) of ligand-stripped nanocrystals are assembled using the same structure-directing block copolymers, which contain a tethering domain designed to adsorb to their naked surfaces. Material compositions range from metal oxides (Sn-doped In(2)O(3) or ITO, CeO(2), TiO(2)) to metal fluorides (Yb,Er-doped NaYF(4)) and metals (FePt). The incorporation of new types of nanocrystals into mesoporous architectures can lead to enhanced performance. For example, TiO(2) nanorod-based materials withstand >1000 electrochemical cycles without significant degradation.