Redox active or thiol reactive? Optimization of rapid screens to identify less evident nuisance compounds

Compounds that exhibit assay interference or undesirable mechanisms of bioactivity are routinely encountered in assays at various stages of drug discovery. We observed that assays for the investigation of thiol-reactive and redox-active compounds have not been collected in a comprehensive review. Here, we review these assays and subject them to experimental optimization to improve their reliability. We demonstrate the usefulness of our assay cascade by assaying a library of bioactive compounds, chemical probes, and a set of approved drugs. These high-throughput assays should complement the array of wet-lab and in silico assays during the initial stages of hit discovery campaigns to pursue only hit compounds with tractable mechanisms of action.     

Impact of different types of olive oil on cardiovascular risk factors: A systematic review and network meta-analysis

Background and aimThis network meta-analysis (NMA) compares the effects of different types of olive oil (OO) on cardiovascular risk factors.Methods and resultsLiterature search was conducted on three electronic databases (Medline, Web of Science, and Cochrane Central). Inclusion criteria: Randomized controlled trials (RCTs) (≥3 weeks duration of intervention) comparing at least two of the following types of OO: refined OO (ROO), mixed OO (MOO), low phenolic (extra) virgin OO (LP(E)VOO), and high phenolic (extra) virgin OO (HP(E)VOO). Random-effects NMA was performed for seven outcomes; and surface under the cumulative ranking curve (SUCRA) was estimated, using an analytical approach (P-score). Thirteen RCTs (16 reports) with 611 mainly healthy participants (mean age: 26–70 years) were identified. No differences for total cholesterol, HDL-cholesterol, triacylglycerols, and diastolic blood pressure were observed comparing ROO, MOO, LP(E)VOO and HP(E)VOO. HP(E)VOO slightly reduce LDL-cholesterol (LDL-C) compared to LP(E)VOO (mean difference [MD]: −0.14 mmol/L, 95%–CI: −0.28, −0.01). Both, HP(E)VOO and LP(E)VOO reduces SBP compared to ROO (range of MD: −2.99 to −2.87 mmHg), and HP(E)VOO may improve oxidized LDL-cholesterol (oxLDL-C) compared to ROO (standardized MD: −0.68, 95%–CI: −1.31, −0.04). In secondary analyses, EVOO may reduce oxLDL-C compared to ROO, and a dose-response relationship between higher intakes of phenolic compounds from OO and lower SBP and oxLDL-C values was detected. HP(E)VOO was ranked as best treatment for LDL-C (P-score: 0.83), oxLDL-C (0.88), and SBP (0.75).ConclusionsHP(E)VOO may improve some cardiovascular risk factors, however, public health implications are limited by overall low or moderate certainty of evidence.     

Chalcone hybrids and their antimalarial activity

Malaria, one of the most striking, re-emerging infectious diseases caused by the genus Plasmodium, places a huge burden on global healthcare systems. A major challenge in the control and eradication of malaria is the continuous emergence of increasingly widespread drug-resistant malaria, creating an urgent need to develop novel antimalarial agents. Chalcone derivatives are ubiquitous in nature and have become indispensable units in medicinal chemistry applications due to their diverse biological profiles. Many chalcone derivatives demonstrate potential in vitro and in vivo antimalarial activity, so chalcone could be a useful template for the development of novel antimalarial agents. This review covers the recent development of chalcone hybrids as antimalarial agents. The critical aspects of the design and structure–activity relationship of these compounds are also discussed.     

Ethyl lactate as a potential green solvent to extract hydrophilic (polar) and lipophilic (non-polar) phytonutrients simultaneously from fruit and vegetable by-products

Phytonutrients extracted from natural resources are receiving much attention among researchers due to their highly antioxidative characteristics which prevent several degenerative diseases including cardiovascular diseases and cancers. These nutraceutical compounds can be used in food, pharmaceutical and cosmetic products as natural antioxidants, preservatives, colourants and functional foods. Huge volume of food wastes are generated from the processing industry and these low-value food residues are rich in various phytonutrients worth recovering. This approach of valorisation reduces the generation of food wastes and is cost-effective considering the cheap feedstock, reduced waste management expenses and high market value of extracted compounds. In light of the health and safety risks posed by commonly used organic extraction solvents derived from the petrochemical industry, there is a need to recover the phytonutrients using green, sustainable and efficient solvents that are safe for human consumption. This work discusses ethyl lactate as a safe, green, efficient and potentially cheap solvent to recover phytonutrients from fruit and vegetable by-products. Ethyl lactate is compared with other organic solvents commonly used from the aspects of safety, environmental impacts and efficiency. Current challenges when employing ethyl lactate are also discussed.     

Antimicrobial activities of novel bipyridine compounds produced by a new strain of Saccharothrix isolated from Saharan soil

The actinobacterium strain ABH26 closely related to Saccharothrix xinjiangensis, isolated from an Algerian Saharan soil sample, exhibited highly antagonist activity against Gram-positive bacteria, yeasts and filamentous fungi. Its ability to produce antimicrobial compounds was investigated using several solid culture media. The highest antimicrobial activity was obtained on Bennett medium. The antibiotics secreted by strain ABH26 on Bennett medium were extracted by methanol and purified by reverse-phase HPLC using a C18 column. The chemical structures of the compounds were determined after spectroscopic (¹H NMR, ¹³C NMR, ¹H-¹H COSY and ¹H-¹³C HMBC spectra), and spectrometric (mass spectrum) analyses. Two new cyanogriside antibiotics named cyanogriside I (1) and cyanogriside J (2), were characterized along with three known caerulomycins, caerulomycin A (3), caerulomycin F (4) and caerulomycinonitrile (5). This is the first report of cyanogrisides and caerulomycins production by a member of the Saccharothrix genus. The minimum inhibitory concentrations (MIC) of these antibiotics were determined against pathogenic microorganisms.     

中药栀子超临界萃取物的挥发性成分研究

研究了栀子萃取的最佳工艺条件及其挥发油中的化学成分。以L9（3^4）正交设计对超临界萃取条件进行优化，GC-MS联用技术对挥发性成分进行定性及半定量分析。结果显示：55℃，35MPa，120min的萃取条件下挥发性成分的收率最高，超临界萃取产物的主要成分为亚油酸，棕榈酸，反，反-2，4-癸二烯醛，而传统水蒸汽蒸馏工艺下主要成分为反，反-2，4-癸二烯醛。与水蒸汽蒸馏工艺相比较。超临界流体萃取工艺且有革取率高。生产周期短的优点．     

B超引导下经皮穿刺囊内注射铝溶液治疗肾囊肿

在 B 超引导下经皮穿刺囊内注射铝溶液治疗肾囊肿72例89个囊肿结果:消失48个,有效36个,总有效率94%。随访3个月至2年未见复发。其方法安全、简便、无副作用。并对铝溶液作用机制进行初步探讨。     

Release of corrosion products from amalgam in phosphate containing solutions

Abstract— The effect of phosphate concentration on corrosion was compared for two types of amalgam: a conventional alloy (ANA 68) and a high-Cu admixed alloy (Dispersalloy). The test specimens were stored for 4 months in electrolytes containing 85 mM NaCl and 85 mM NaCl with 2.5, 10, or 100 mM phosphate buffer respectively. The solutions were renewed each month and analyzed for Cu, Zn, Sn, Hg, and Ag in an atomic absorption spectrophotometer. The surfaces and cross-sections of the specimens were studied in a scanning electron microscope (SEM) with an energy dispersive detector (EDAX). The corrosion products, mainly Sn-compounds, at the surface of the amalgams were less in the solutions containing high concentrations of phosphate. In cross-section subsurface corrosion of the high-Cu amalgam was observed especially in specimens immersed in the NaCl solution without phosphate. The conventional amalgam showed surface corrosion only. The decrease in release of elements with time from the conventional amalgam in all the experimental solutions might indicate passivation. For the high-Cu amalgam the release of elements increased with time, except for Cu and Sn in the solution with 100 mM phosphate, indicating that phosphate inhibits corrosion of the Cu-Sn-phases. Release of corrosion products from the high-Cu amalgam was more dependent on the presence of phosphate than the conventional amalgam.