New resveratrol analogs as improved biologically active structures: Design, synthesis and computational modeling.

New analogs of the well-known bioactive trihydroxy-stilbene resveratrol were synthesized to investigate their potential biological activity. The focus was on assessing their ability to inhibit cholinesterase enzymes (ChEs) and their antioxidative properties, which were thoroughly examined. New resveratrol analogs were synthesized through Wittig or McMurry reaction in moderate-to-good yields. In all synthetic pathways, mixtures of cis- and trans-isomers were obtained, then separated by chromatography, and trans-isomers were isolated as targeted structures. The stilbene derivatives underwent evaluation for antioxidant activity (AOA) using DPPH and CUPRAC assay, and their potential to inhibit acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) was also measured. The biological tests have shown that the same compounds exhibited significant antioxidative and butyrylcholinesterase inhibitory potential, as evidenced by lower IC50 values compared to the established standards, trans-resveratrol, and galantamine, respectively. Additionally, molecular docking of the selected synthesized potential inhibitors to the enzyme's active site was performed, followed by assessing the complex stability using molecular dynamics simulation lasting 100 ns. Lastly, the new compounds underwent examination to determine their potential mutagenicity.

Synthesis, photochemistry and computational study of novel 1,2,3-triazole heterostilbenes: Expressed biological activity of their electrocyclization photoproducts.

New 1,2,3-triazolostilbenes were synthesized and photochemically transformed to substituted naphthotriazoles as electrocyclization products in high isolated yields for studying the acetyl- and butyrylcholinesterase inhibitory and anti-inflammatory activity. The best experimental results showed the naphthotriazole photoproducts providing interesting observation on cholinesterase inhibition associated with the inhibition of TNFα cytokine production. The geometries of synthesized triazolostilbenes were computationally examined using Density Functional Theory (DFT), followed by time-dependent DFT calculations to obtain insight into electronic properties observed by UV-Vis spectroscopy. The complexes between selected compounds with the active site of AChE are assessed by docking. A quantum mechanical cluster approach was utilized to optimize their structures, thus providing insight into the stabilizing interactions between the potential inhibitor and the active site.

Letter to the Editor: Comparing the Novel Parameter 'Slope of the Steepest Part of Hemolysis Curve' to Standard Median Corpuscular Fragility for Evaluating Erythrocyte Stability during Prolonged Storage.

OBJECTIVE: Several ways for presenting the results of osmotic fragility test have been described in the literature. Our aim was to compare the utility of a novel parameter for assessment of erythrocyte osmotic properties, i.e., 'Slope of the steepest part of hemolysis curve' with the most frequently used parameter 'Median corpuscular fragility' in order to assess the stability of erythrocytes in a blood sample during prolonged storage. METHODS: Ten whole blood samples were obtained from healthy donors. The osmotic fragility test was initially conducted on the day of venipuncture, and subsequent analyses were carried out on days 1, 2, 4, 7, 9, 11, and 14 after the venipuncture. Mean hemolysis percentage values were used to construct hemolysis curves. The steepest parts of hemolysis curves were estimated to be linear, and lines that overlapped those parts of the curves were created. The slope of these lines was calculated, and the resulting mean values are presented. RESULTS: A significant increase in Median corpuscular fragility values was observed, starting from day of venipuncture. We compared the average values for each day of analysis. The first significant difference in Median corpuscular fragility values was observed on day 4 compared to the day of venipuncture (p=0.006), with values 0.53±0.030 % and 0.41±0.014% respectively. Meanwhile, differences in the values of the slopes of the steepest parts of hemolysis curves were observed as early as day 2 when compared to the day of venipuncture (p=0.046), with values of -966.23±233.07 and -588.01±222.85, respectively. CONCLUSION: Prolonged storage of whole blood samples leads to an increase in osmotic fragility and alters the shape of the hemolysis curve. These changes suggest that postponing the osmotic fragility test could lead to diagnostic inaccuracies. These findings suggest that slope value is a more accurate parameter for evaluating erythrocyte stability during storage, compared to commonly used Median corpuscular fragility value. Hence, it has potential importance and can be complementary to the laboratory result of the OFT. Therefore, it can be useful to provide these results jointly with the results of the OFT test.

New naphtho/thienobenzo-triazoles with interconnected anti-inflammatory and cholinesterase inhibitory activity.

New 1,2,3-triazolo(thieno)stilbenes were synthesized by Wittig reaction and photochemically transformed to corresponding substituted thienobenzo/naphtho-triazoles in high isolated yields. They were prepared to study the acetyl- and butyrylcholinesterase inhibition associated with the inhibition of TNFα cytokine production and anti-inflammatory activity. The best experimental results were achieved with the allyl-thienobenzotriazole and isopropyl, p-methoxybenzyl, and hydroxybutyl substituted naphthotriazoles bearing additional chloro or methoxy groups. The allyl-thienobenzotriazole photoproduct is twice as potent an inhibitor of eqBChE compared to the standard galantamine. At the same time, this compound strongly inhibited TNFα production in PBMCs in response to the LPS stimulus. The complexes between selected compounds with the active site of BChE and AChE are assessed by docking, providing insight into the stabilizing interactions between the potential inhibitor and the active site.

The occurrence of lipophilic toxins in shellfish from the Middle Adriatic Sea.

The first survey of the phycotoxin profile in mussels (Mytilus galloprovincialis) from the coastal waters of Bosnia and Herzegovina (The Bay of Neum, Middle Adriatic Sea) in correlation to the Makarska City Bay (Croatia, Middle Adriatic Sea) was conducted in 2017. Throughout the monitoring period, occasions of gymnodimine (GYM) and azaspiracid (AZA2) shellfish toxicity were recorded in concentrations that do not endanger human health. The occurrence of yessotoxins (YTXs), the most common toxins found in the Adriatic Sea, was correlated to the presence of the Gonyaulax species, a potential source of YTX. The DSP group of toxins is represented by the ester-OA. Phytoplankton analysis confirmed the presence of dinoflagellates from the Prorocentrum genus, a species associated with DSP toxicity. Occurrence frequency and variability of toxin composition were investigated in conjunction to physico-chemical parameters in the surrounding sea water. In the central Adriatic Sea, the infestation period ranges in general from June to August. However, the depuration phase extended beyond September in the Bay of Neum, increasing the length of the decontamination period.