Introducing the INSIGNIA project: Environmental monitoring of pesticides use through honey bees

INSIGNIA aims to design and test an innovative, non-invasive, scientifically proven citizen science environmental monitoring protocol for the detection of pesticides via honey bees. It is a pilot project initiated and financed by the European Commission (PP-1-1-2018; EC SANTE). The study is being carried out by a consortium of specialists in honey bees, apiculture, chemistry, molecular biology, statistics, analytics, modelling, extension, social science and citizen science from twelve countries. Honey bee colonies are excellent bio-samplers of biological material such as nectar, pollen and plant pathogens, as well as non-biological material such as pesticides or airborne contamination. Honey bee colonies forage over a circle of about 1 km radius, increasing to several km if required depending on the availability and attractiveness of food. All material collected is concentrated in the hive, and the honey bee colony can provide four main matrices for environmental monitoring: bees, honey, pollen and wax. For pesticides, pollen and wax are the focal matrices. Pollen collected in pollen traps will be sampled every two weeks to record foraging conditions. During the season, most of pollen is consumed within days, so beebread can provide recent, random sampling results. On the other hand wax acts as a passive sampler, building up an archive of pesticides that have entered the hive. Alternative in-hive passive samplers will be tested to replicate wax as a “pesticide-sponge”. Samples will be analysed for the presence of pesticides and the botanical origin of the pollen using an ITS2 DNA metabarcoding approach. Data on pollen and pesticides will be then be combined to obtain information on foraging conditions and pesticide use, together with evaluation of the CORINE database for land use and pesticide legislation to model the exposure risks to honey bees and wild bees. All monitoring steps from sampling through to analysis will be studied and tested in four countries in year 1, and the best practices will then be ring-tested in nine countries in year 2. Information about the course of the project and its results and publications will be available in the INSIGNIA website www.insignia-bee.eu.info:eu-repo/semantics/publishedVersio

Synthesis of novel conformationally constrained pyrazolo[4,3-c]quinoline derivatives as potential ligands for the estrogen receptor

The preparation of three novel classes of pyrazolo[4,3-c]quinoline derivatives is reported. The easily accessible 2,3-dihydro-1H-quinolin-4-ones were used as the starting materials and were functionalized with three different acylating agents affording their respective constrained core substrates. The latter by condensation with phenyl(or 4-methoxyphenyl)hydrazines and subsequent debenzylation or demethylation provided the desired pyrazole derivatives. Some interesting features emerged with respect to the regioselectivity and mechanism of these reactions. © Georg Thieme Verlag Stuttgart

Determination of dimethoate and omethoate in human serum samples. Risk assessment for the operator

A simple and effective analytical procedure has been developed for the determination of dimethoate (DIM) residues and its metabolite, omethoate, in serum samples of pesticide operators. For the selection of the most appropriate method for sample treatment, techniques such as headspace solid phase micro extraction and solid phase extraction and liquid-liquid extraction were applied. The applied method was based on toluene (2 mL) extraction of a 0.5mL serum sample. In this report, it was observed that DIM concentration level affected the ratio of the area response of DIM and one of its oxygenated metabolite, omethoate. In this context, higher concentrations favoured the predominance of DIM while lower concentrations lead to the formation of omethoate. The method was validated using human serum samples spiked with DIM. Good linearity was obtained in the range of 1-10 ng/mL co-calculating DIM and omethoate. Various concentrations of DIM were mixed with serum and stored up to five days at -20°C. Recoveries ranged from 72% to 88% at two spiking levels for six replicates. The detection and quantification limit were calculated at 0.12 and 0.36 ng/mL of serum, respectively. Finally the comparison with the Acceptable Operator Exposure Level (AOEL) of DIM revealed that the maximum exposure of the operators reached the 30% of the AOEL for only two cases. © 2011 Taylor & Francis

Novel carbamοyloxy analogues of tamoxifen: Synthesis, molecular docking and bioactivity evaluation

Background: Tamoxifen (TAM), a non-steroidal antiestrogen, constitutes the endocrine treatment of choice against breast cancer. Since its inauguration, substantial effort has been devoted towards the design and synthesis of TAM’s analogues aiming to improve its bioactivity and reveal their structure-activity relationship. Objective: One of the most studied synthetic features of TAM’s structure is the ether side chain, which is strongly related to its positioning into the active site of the Estrogen Receptors (ERα and ERβ). Herein, we present the application of a straightforward route for the efficient synthesis of selected novel carbamoyloxy analogues of TAM and the evaluation of their respective binding affinities to the Estrogen Receptors α and β. Methods: A one-pot reaction was applied for the construction of TAM’s triarylethylene core moiety, which subsequently was derivatized to provide efficiently the target carbamoyloxy analogues of TAM. The Z and E isomers of the latter were separated using RP-HPLC-UV and their binding affinities to ERα and ERβ were measured. Results: Among all compounds synthesized, the dimethyl derivative was determined as the most potent for both receptors, displaying binding affinity values comparable to TAM, though the Z-diethyl analogue maintained substantial affinity to both ERs. The aforementioned results were further studied by theoretical calculations and molecular modelling to delineate a concordance among calculations and biological activity. Conclusion: Approach applied herein permitted the extraction of a useful structure-activity relationship correlation pattern highlighting the importance of a chemically stabilized tamoxifen side chain. © 2021 Bentham Science Publishers

Novel pyrazole derivatives: Synthesis and evaluation of anti-angiogenic activity

The synthesis of a series of novel trisubstituted pyrazole derivatives and their PIFA-mediated conversion to molecules bearing the fused pyrazolo[4,3-c]quinoline ring system is reported. The anti-angiogenic activity of these compounds was evaluated by using in vitro assays for endothelial cell proliferation and migration, and in the chicken chorioallantoic membrane (CAM) assay. Compounds containing the fused pyrazolo[4,3-c]quinoline motifs emerged as potent anti-angiogenic compounds, which also had the ability to inhibit the growth of human breast (MCF-7) and cervical (Hela) carcinoma cells in vitro. \ua9 2010 Elsevier Ltd. All rights reserved

Synthesis of novel nitro-substituted triaryl pyrazole derivatives as potential estrogen receptor ligands

Novel tetrasubstituted pyrazole derivatives bearing a nitro substituent on their A-phenol ring were synthesized and their binding affinity towards the estrogen receptor (ER) subtypes ERα and ERβ was determined. Among compounds tested, the 2-nitrophenol derivative 5c was found to bind satisfactorily to both estrogen receptor subtypes (RBAα=5.17 and RBAβ=3.27). In general, the introduction of a nitro group into the A ring of these compounds was found to benefit their ERβ binding abilities. © 2007 by MDPI

Synthesis of (R)-dihydropyridones as key intermediates for an efficient access to piperidine alkaloids

The efficient transformation of D-glucal to (2R)- hydroxymethyldihydropyridinone 5 in seven steps and 35 % overall yield is reported. Dihydropyridone 5 constitutes a versatile chiral building block for the synthesis of various piperidine alkaloids. In this regard, 5 was converted to piperidinol 13 and piperidinone 15, that may be further elaborated for the syntheses of (+)-desoxoprosophylline (1) and deoxymannojirimycin (3) or D-mannolactam (4), respectively. © 2007 by MDPI

Determination of trace inorganic germanium in bis-beta-carboxyethyl-germanium sesquioxide by headspace solid-phase microextraction and gas chromatography - mass spectrometry

Organic germanium compounds, such as bis-beta-carboxyethylgermanium sesquioxide ("Ge-132"), have attained widespread distribution - particularly in self-medication - and are applied as tonics due to their presumed anticancer activities. In general, the toxicity of this particular organo-germanium compound is low. In contrast to this, acute and chronic toxic effects of inorganic germanium dioxide (GeO2) have been demonstrated. In this paper, chloride-generation headspace solid-phase microextraction (SPME) coupled with gas chromatography-mass spectrometry (GC-MS) is proposed as a technique for the determination of trace amounts of GeO2 in Ge-132. This method takes advantage of the fact that Ge-132 is not able to generate volatile species upon reaction with conc. HCl. The conditions for the generation of germanium chloride (GeCl4), such as SPME fibre selection, extraction time and HCl concentration were investigated. The detection limit was established at 0.28 ug/ml (as Ge). Thus, this approach provides a novel, simple and fast platform for the determination of inorganic Ge in organogermanium formulations. © 2013 Bentham Science Publishers

PIFA-mediated synthesis of novel pyrazoloquinolin-4-ones as potential ligands for the estrogen receptor

A facile and efficient preparation of pyrazoloquinolin-4-ones, as potential ligands for the estrogen receptor, via a PIFA [phenyliodine(III)bis(trifluoroacetate)] promoted cyclization reaction with overall yields up to 29% over six steps is described. The employed strategy, based on an electrophilic amidation reaction as the key step of the synthesis, allows the generation of a diverse array of derivatives. © 2008 Elsevier Ltd. All rights reserved