Synthesis of benzylidene-benzofuranone derivatives as probes for detection of amyloid fibrils in cells.

Aggregated protein is the common cause of a wide variety of neurodegenerative diseases, such as Alzheimer's disease (AD), Parkinson's disease, etc. It is proven that protein aggregation like amyloid β (Aβ) is one of the critical factors causing AD and, its diagnosis in the early stages of the disease is important for the treatment or prevention of AD. To have a better understanding of protein aggregation and its pathologies, there is a huge need to design and develop new and more trustworthy probe molecules for amyloid quantification and amyloid imaging.

Discovery of Potent Cholinesterase Inhibition-Based Multi-Target-Directed Lead Compounds for Synaptoprotection in Alzheimer's Disease.

Drug development efforts that focused on single targets failed to provide effective treatment for Alzheimer's disease (AD). Therefore, we designed cholinesterase inhibition (ChEI)-based multi-target-directed ligands (MTDLs) to simultaneously target AD-related receptors. We built a library of 70 compounds, sequentially screened for ChEI, and determined σR, σR, NMDAR-GluN2B binding affinities, and P2X7R antagonistic activities.

Selected Natural and Synthetic Agents Effective against Parkinson's Disease with Diverse Mechanisms.

Similar to other neurodegenerative diseases, Parkinson's disease (PD) has been extensively investigated with respect to its neuropathological background and possible treatment options. Since the symptomatic outcomes are generally related to dopamine deficiency, the current treatment strate-gies towards PD mainly employ dopaminergic agonists as well as the compounds acting on dopamine metabolism. These drugs do not provide disease modifying properties; therefore alternative drug dis-covery studies focus on targets involved in the progressive neurodegenerative character of PD.

The Hybrid Compounds as Multi-target Ligands for the Treatment of Alzheimer's Disease: Considerations on Donepezil.

The strategies to combat Alzheimer's Disease (AD) have been changing with respect to the failures of many drug candidates assessed in clinical studies, the complex pathophysiology of AD, and the limitations of the current drugs employed. So far, none of the targets, either validated or nonvalidated, have been shown to be purely causative in the generation and development of AD. Considering the progressive and the neurodegenerative characteristics of the disease, the main strategy has been based on the design of molecules capable of showing activity on more than one receptor, and it is defined as multi-target ligand design strategy.

The investigation of fluorescence and metal interaction properties of racemic 7,8,9,10-tetrahydro-3-hydroxy-4-(1-hydroxyethyl)benzo[c]chromen-6-one.

The design or investigation of fluorescence probes continues to receive attention with respect to the diverse applications of spectrofluorometry. Depending on the highly sensitive character, fluorescence spectroscopy-based methodologies have been widely used in recent years in different sciences, including analytical, environmental, and medicinal chemistry areas. In our previous works, we have shown the iron (III) selective on-off sensor properties of benzo[c]chromen-6-one derivatives.

3-Hydroxy-7,8,9,10-tetrahydro-6H-benzo[c]chromen-6-one and 3-hydroxy-6H-benzo[c]chromen-6-one act as on-off selective fluorescent sensors for Iron (III) under in vitro and ex vivo conditions.

Regarding the abundant use of metals for different purposes, it becomes more critical from various scientific and technological perspectives to discover novel agents as selective probes for the detection of specific metals. In our previous studies, we have shown that aqueous solutions of natural urolithins (i.e.

Prioritizing potential ACE2 inhibitors in the COVID-19 pandemic: Insights from a molecular mechanics-assisted structure-based virtual screening experiment.

Angiotensin-converting enzyme 2 (ACE2) is a membrane-bound zinc metallopeptidase that generates the vasodilatory peptide angiotensin 1-7 and thus performs a protective role in heart disease. It is considered an important therapeutic target in controlling the COVID-19 outbreak, since SARS-CoV-2 enters permissive cells via an ACE2-mediated mechanism. The present in silico study attempted to repurpose existing drugs for use as prospective viral-entry inhibitors targeting human ACE2.

Synthesis, Characterization, Molecular Docking, and Biological Activities of Some Natural and Synthetic Urolithin Analogs.

Urolithins (that is, hydroxy substituted benzo[c]chromen-6-one derivatives) are formed within the gastrointestinal tract following to the exposure to various ellagitannin rich diet, particularly involving pomegranate, nuts, and berries. Regarding the bioavailability deficiency of ellagitannins, the biological activities obtained through the extracts of these dietaries are attributed to the urolithin compounds, since they are bioavailable. Particularly, there are studies indicating the importance of ellagitannin-rich food for protective and alternative treatment of Alzheimer's Disease (AD).

Urolithin A and B Derivatives as ON-OFF Selective Fluorescent Sensors for Iron(III).

The detection and sensing of environmentally crucial metal ions has always been of great significance in various fields such as biological and environmental cycles. Our previous studies have indicated a new coumarin based lactone, Urolithin B (i.e.

Benzimidazole-derived Compounds Designed for Different Targets of Alzheimer's Disease.

Benzimidazole scaffold has been efficiently used for the design of various pharmacologically active molecules. Indeed, there are various benzimidazole drugs, available today, employed for the treatment of different diseases. Although there is no benzimidazole moiety containing a drug used in clinic today for the treatment of Alzheimer's Disease (AD), there have been many benzimidazole derivative compounds designed and synthesized to act on some of the validated and non-validated targets of AD.

Porous magnetic resin-g-chitosan beads for adsorptive removal of phenolic compounds.

In this study, porous magnetic resin grafted chitosan (R-g-Ch) beads were prepared for removal of 4-chlorophenol and phenol from aqueous solutions. The R-g-Ch beads were characterized by vibrating sample magnetometer, Fourier-transform infrared spectroscopy, scanning electron microscopy and thermogravimetry methods. The removal of the phenolic compounds was optimized by varying the experimental conditions.

Urolithin B as a Simple, Selective, Fluorescent Probe for Sensing Iron(III) in Semi-Aqueous Solution.

The development of simple, environmental friendly, and cheap reagents with metal binding properties are quite important not only for the treatment of environmental pollution but also for their application in medicine. Within this study, for the first time, we displayed a natural chromen analogue, Urolithin B, as a simple, selective, fluorescent iron (III) sensing probe. Following the synthesis and structure identification studies, the selective metal binding property of the compound was displayed employing fluorescence techniques.

Traditional Techniques Applied in Olive Oil Production Results in Lower Quality Products in Northern Cyprus.

Objectives: Olive oil production and its consumption is one of the traditional characteristics of Northern Cyprus. To date, no research has been conducted to analyze the quality of traditionally produced olive oil. Therefore, within this study, we aimed to analyze the olive oil produced within the island concomitant to the determination and comparison of its quality indices.

Synthesis of Novel Benzothiazole-Piperazine Derivatives and Their Biological Evaluation as Acetylcholinesterase Inhibitors and Cytotoxic Agents.

Objective And Method: A new series of benzothiazole-piperazine derivatives was synthesized and a complete chemical characterization of the novel compounds was provided. In vitro cytotoxic activities were screened against colorectal (HCT-116), breast (MCF-7) and hepatocellular (Huh7) cancer cell lines by Sulforhodamine B assay.

Result And Discussion: All compounds showed cytotoxic activity against hepatocellular (Huh7) and breast (MCF-7) cancer cell lines.

Assessment of Aflatoxin M1 and Heavy Metal Levels in Mothers Breast Milk in Famagusta, Cyprus.

Breast milk contributes towards optimal nutrition for infants. However, studies showed that it can also contain different toxins and heavy metals, which reduce its health benefits. The aim of this study is to determine the level of contaminants such as aflatoxin M1 (AFM1), Pb, Cd, As, and Hg in breast milk samples from Famagusta, Cyprus.

Substrate inhibition in human hydroxysteroid sulfotransferase SULT2A1: studies on the formation of catalytically non-productive enzyme complexes.

The cytosolic sulfotransferase hSULT2A1 is the major hydroxysteroid (alcohol) sulfotransferase in human liver, and it catalyzes the 3'-phosphoadenosine-5'-phosphosulfate (PAPS)-dependent sulfation of various endogenous hydroxysteroids as well as many xenobiotics that contain alcohol and phenol functional groups. The hSULT2A1 often displays substrate inhibition, and we have hypothesized that a key element in this response to increasing substrate concentration is the formation of non-productive ternary dead-end enzyme complexes involving the nucleotide product, adenosine 3',5'-diphosphate (PAP). One of these substrates for hSULT2A1 is dehydroepiandrosterone (DHEA), a major circulating steroid hormone in humans that serves as precursor to both androgens and estrogens.

Pentachlorophenol and other chlorinated phenols are substrates for human hydroxysteroid sulfotransferase hSULT2A1.

Pentachlorophenol (PCP) is a persistent chemical contaminant that has been extensively investigated in terms of its toxicology and metabolism. Similar to PCP, other chlorinated phenol derivatives are also widely present in the environment from various sources. Even though some of the chlorine-substituted phenols, and particularly PCP, are well-known inhibitors of phenol sulfotransferases (SULTs), these compounds have been shown to undergo sulfation in humans.

4-(5-chloro-2(3H)-benzoxazolon-3-yl) butanoic acid derivatives: synthesis, antinociceptive and anti-inflammatory properties.

In this study, 4-(5-chloro-2(3H)-benzoxazolone-3-yl)butanoic acid and its ethyl ester as well as its ten new amide derivatives have been synthesized. Their structures have been elucidated by IR, (1)H-NMR spectra and elemental analysis. The compounds were screened for antinociceptive and anti-inflammatory activities.