9-(4'-dimethylaminophenyl)-2,6,7-trihydroxy-xanthene-3-one is a potentially novel antiplatelet drug which antagonizes the effect of thromboxane A2

Background: Currently, used oral antiplatelet drugs are both limited and associated with the risk of treatment failure/resistance. Research in this area is hence highly desired. A series of xanthene-3-ones derivatives, we had synthesized, showed us that these derivatives had antiplatelet activity. As far as we know, no research on the effects of xanthen-3-ones in this area has been done. Objective: The aim was to study the antiplatelet potential of a series of synthesised 9-phenylxanthene- 3-ones and to find the ideal structural feature(s) for antiplatelet potential and determine the mechanism of action. Methods: The compounds were synthesized from 1,2,4-triacetoxybenzene and various benzaldehydes. The reaction proceeded smoothly under acidic alcoholic conditions, furnishing the desired products in good yields. The compounds were first screened in whole human blood where platelet aggregation was induced by arachidonic acid. Further analysis was targeted at search of the mechanism of action. Results: Initial screening showed that a majority of the synthesized derivatives had substantial antiplatelet potential. None of the compounds were able to block cyclooxygenase 1 or thromboxane synthase. The mechanism appeared to be based on antagonism of thromboxane effects. The most potent compound 9-(4'-dimethylaminophenyl)-2,6,7-trihydroxy-xanthene-3-one had better potential to block collagen induced platelet aggregation than clinically used acetylsalicylic acid. Conclusion: The last mentioned derivative is promising for further in vivo testing

SYNTHESIS OF BISCOUMARIN DERIVATIVES AS ANTIMICROBIAL AGENTS

Objective: As a further part of our chemical and biological studies in this field, we describe the preparations of the properly substituted benzylidene-bis-(4-hydroxycoumarin) derivatives 5a-h and 3-(6-oxo-(1H)-benzopyrano[4,3-b]benzopyran-7-yl)-4-hydroxycoumarin derivatives 6a-e. Methods: The synthesized compounds were screened for their in vitro antimicrobial activity against five strains of bacteria and two fungal strains using disk diffusion assay and dilution method. The way in which the substituent group's physicochemical properties influence the antimicrobial activity is discussed in the paper. Results: The in vitro evaluation of their inhibitory properties towards five strains of Gram-positive and Gram-negative bacteria and two fungal strains indicated that the                                       4-trifluoromethylbenzylidene derivative of bis-(4-hydroxycoumarin) (compound 5c) and                    3-(6-oxo-(1H)-18-bromobenzopyrano[4,3-b]benzopyran-7-yl)-4-hydroxycoumarin derivative (compound 6b) possess the most potent antibacterial activities, with MIC of 3.9 μg/mL - 7.8 μg/mL against Gram-positive bacteria. Conclusion: The compound 6b has greater antibacterial activity than the standard chloramfenicol (inhibition zone 26 mm and MIC 1.9 μg/mL) against Staphyloccocus aureus and could be considered as leading compound in the future antimicrobial drug development.   Key words: Benzylidene-bis-(4-hydroxycoumarin), benzopyranocoumarin derivatives, antibacterial assays, antifungal activity

Sadržaj mikro- i makroelementa i procjena zdravstvenog rizika Morchella esculenta i Lactarius piperatus iz Bosne i Hercegovine

The content of micro- and macroelements in dry wild and edible Morchella esculenta and Lactarius piperatus mushrooms collected in Bosnia and Herzegovina was determined using the ICP-OES (inductively coupled plasma optical emission spectrometry) technique. The contents of microelements in M. esculenta and L. piperatus expressed in mg kg–1 DW (dry weight) were as follows: Co 0.08 and 0.28, Cu 37.35 and 27.66, Fe 174.29 and 28.11, Mn 21.26 and 19.31, Se 0.46 and 0.52, Zn 122.84 and 45.06, Al 27.80 and 24.80, Cr 0.83 and 1.06, Ni 0.99 and 0.96, As 0.32 and 0.09, Cd 0.48 and 0.13, and Pb 0.61 and 0.12, respectively, while the contents of macroelements were: K 26989.48 and 36117.20, Na 70.85 and 28.60, Ca 643.48 and 271.93, Mg 684.16 and 840.64, S 2329.33 and 610.42, and P 10339.35 and 5107.63, respectively. In this study, the potential health risks of heavy metals were assessed, and target hazard quotient (THQ) for As, Cd, Pb, Cu, Zn, Ni, and Cr in the tested mushrooms was lower than the safe level. Edible wild mushrooms M. esculenta and L. piperatus, according to this study, could be used in human nutrition due to their favourable characteristics. Based on the accumulations of heavy metals in the tested mushrooms, it was shown that the collection surfaces are environmentally acceptable. Mushrooms collected from this area are generally safe to eat and pose no health risks to humans.Sadržaj mikro i makroelemenata u sušenim divljim jestivim gljivama Morchella esculenta i Lactarius piperatus prikupljenim u Bosni i Hercegovini određen je tehnikom ICP-OES (induktivno spregnuta plazma s optičkom emisijskom spektrometrijom). Sadržaj mikroelemenata kod M. esculenta i L. piperatus izražen u mg kg–1 suhe težine bio je sljedeći: Co 0,08 i 0,28, Cu 37,35 i 27,66, Fe 174,29 i 28,11, Mn 21,26 i 19,31, Se 0,46 i 0,52, Zn 122,84 i 45,06, Al 27,80 i 24,80, Cr 0,83 i 1,06, Ni 0,99 i 0,96, As 0,32 i 0,09, Cd 0,48 i 0,13, te Pb 0,61 i 0,12, dok je sadržaj makroelemenata bio: K 26989,48 i 36117,20, Na 70,85 i 28,60, Ca 643,48 i 271,93, Mg 684,16 i 840,64, S 2329,33 i 610,42, te P 10339,35 i 5107,63. U ovom radu procijenjeni su potencijalni zdravstveni rizici teških metala, a kvocijent ciljane opasnosti (THQ) za As, Cd, Pb, Cu, Zn, Ni i Cr u ispitivanim gljivama bio je niži od sigurnosne razine. Prema rezultatima istraživanja, divlje jestive gljive M. esculenta i L. piperatus, zbog svojih povoljnih karakteristika, mogle bi se upotrebljavati u ljudskoj prehrani. Podatci o akumuliranosti teških metala u ispitivanim gljivama pokazali su da su sabirne površine ekološki prihvatljive, a gljive sigurne za jelo

Antimicrobial Activity and Docking Study of Synthesized Xanthen-3-on Derivatives

Twelve previously synthesized biologically active 2,6,7-trihydroxy-9-aryl-3H-xanthen-3-one derivatives (1-12) were evaluated in vitro for their antimicrobial activity against four bacteria, S. aureus, B. subtilis P. aeruginosa and E. coli, and two fungi strains, C. albicans and S. cerevisiae. The most potent compound were derivatives 1 which possess hydroxyl group and bromine as substituent and 11 with bromine as substituent on phenyl ring. The results indicate that bromine increase antimicrobial activity of 2,6,7-trihydroxy-9-aryl-3-Hxanthen-3-one derivatives. Compound 7 with ethoxy substituent on phenyl ring showed the least activity against tested bacteria and fungi strains, which is in line with an earlier observation that ethoxy substitution decreases antimicrobial activity. The most and the least potent compounds were subjected to molecular docking simulations to preliminary find out the potential molecular target and at the same moment further support the experimental antimicrobial test of xanthen derivatives

Antimicrobial Activity and Docking Study of Synthesized Xanthen-3-on Derivatives

Twelve previously synthesized biologically active 2,6,7-trihydroxy-9-aryl-3H-xanthen-3-one derivatives (1-12) were evaluated in vitro for their antimicrobial activity against four bacteria, S. aureus, B. subtilis P. aeruginosa and E. coli, and two fungi strains, C. albicans and S. cerevisiae. The most potent compound were derivatives 1 which possess hydroxyl group and bromine as substituent and 11 with bromine as substituent on phenyl ring. The results indicate that bromine increase antimicrobial activity of 2,6,7-trihydroxy-9-aryl-3-Hxanthen-3-one derivatives. Compound 7 with ethoxy substituent on phenyl ring showed the least activity against tested bacteria and fungi strains, which is in line with an earlier observation that ethoxy substitution decreases antimicrobial activity. The most and the least potent compounds were subjected to molecular docking simulations to preliminary find out the potential molecular target and at the same moment further support the experimental antimicrobial test of xanthen derivatives

Antioxidant, Antimicrobial and Antiproliferative Activities of Synthesized 2,2,5,5-Tetramethyl-9-aryl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione Derivatives

Ten biologically active 2,2,5,5-tetramethyl-9-aryl-3,4,5,6,7,9-hexahydro-1H-xanthene-1,8(2H)-dione derivatives were synthesized and their structures were confirmed by IR, 1H and 13C NMR spectroscopy and mass spectrometry. Synthesized compounds were scanned for their antioxidant, antimicrobial and antiproliferative activity. Antibacterial activity was tested by the diffusion and dilution method against Bacillus subtilis, Staphylococcus aureus, Escherichia coli and Pseudomonas aeruginosa, while antifungal activity was tested against Candida albicans and Saccharomyces cerevisiae. Antiproliferative activity was tested against HeLa (cervical carcinoma), SW620 (colorectal adenocarcinoma, metastatic), hepatocellular carcinoma (HEpG2), lung carcinoma cells (A549) and mouse embryo fibroblast cell line (3T3). The best antioxidant activity showed compound 2 with two hydroxy groups substituted on phenyl ring in positions 2\u27 and 3\u27. The best antimicrobial activity of all synthesized compounds showed compound 8, while the best antiproliferative activity showed compound 6. Results signify the importance of xanthene-1,8-dione derivatives as potential antioxidant and antiproliferative agents. This work is licensed under a Creative Commons Attribution 4.0 International License

9-Aryl Substituted Hydroxylated Xanthen-3-ones: Synthesis, Structure and Antioxidant Potency Evaluation

Oxidative stress is directly related to several diseases and symptoms, where antioxidant compounds, such as xanthenes, may become important in prevention and/or treatmant. Ten biologically active 9-aryl substituted 2,6,7-trihydroxyxanthen-3-one derivatives were synthesized using reliable one-pot synthesis and their structures were confirmed by IR, 1H and 13C NMR spectroscopy and mass spectrometry. Some of the synthesized compounds were scanned for their antioxidant potency using electrochemical method cyclic voltammetry of immobilized microparticles. Substitution of hydrogen at the phenyl ring of 2,6,7-trihydroxy-9-phenylxanthen-3-one with an electron-donating group affected the reducing power of the compounds by lowering the biological oxidation potential. These results signify the importance of xanthen-3-one derivatives as antioxidant agents and their further biological evaluation

Antiproliferative and genotoxic potential of xanthen-3-one derivatives

Twelve previously synthesized, biologically active 2,6,7-trihydroxyxanthen-3-one derivatives were evaluated in vitro for antiproliferative activity. Compounds were screened against HeLa, SW620, HepG2 and A549 tumor cell lines. Compound with the trifluormethyl group on C-4\u27 position of the phenyl ring showed the best inhibitory activity towards HeLa and A549 tumor cells with IC50 of 0.7 µmol L–1 4.1 µmol L–1, resp. Compound with chlorine and fluorine substituents on aryl ring showed the best antiproliferative activity against SW620 with IC50 of 4.1 µmol L–1 and against HepG2 tumor cell line with IC50 of 4.2 µmol L–1. Analyses of cytotoxic and genotoxic potential of the trifluormethyl derivative were performed with cytokinesis-block micronucleus cytome assay in human lymphocyte culture and revealed no genotoxic and cytotoxic effects. The most potent compounds were subjected to molecular docking simulations in order to analyse bindings to molecular targets and, at the same time, further support the results of experimental cytotoxic tests. Docking studies showed sites of importance in forming hydrogen bonds of the most potent compounds with targets of interest

Synthesis of Arylmethylene-bis(3-hydroxy-5,5-dimethylcyclohex-2-en-1-one) Derivatives and Their Effect on Tyrosinase Activity

The objective of this study was to test the inhibitory effect of five newly synthesized arylmethylene-bis(3-hydroxy-5,5-dimethylcyclohex-2-en-1-one) derivatives. The structural characterization and stereochemistry of synthesized compounds were deduced from analyses of experimental FT-IR, 1H, 13C NMR spectra and theoretical methodology of DFT study based on the global chemical reactivity indices calculated using the 6-31G** level of theory. To predict the stability of the newly synthesized compounds, the reactivity descriptors obtained at B3LYP level (Egap, dipole moment, μ, η, ω) were computed. The docking study and the selected quantum chemical descriptors computed for compounds 1−5 exhibit a good agreement. The strongest inhibitors showed 25 to 30 % inhibition of tyrosinase activity. Results were supported by docking studies of the binding of the strongest inhibitors to the enzyme. The results suggest that tetraketones of this type, due to their tyrosinase inhibitory effect, represent potential agents in the treatment of various types of melanomas and skin hyperpigmentation