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Publikacije (54)

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M. Huremović, Majda Srabovic, M. Salihović, E. Pehlić

Fexofenadine hydrochloride (FFN), (±)-4-[1-hydroxy-4[4-(hydroxydiphenylmethyl)-1-piperidinyl]-butyl] α,α-dimethylbenzeneacetic acid hydrochloride, is a second-generation antihistamine that is used to treat allergies. The drug is highly hydrophobic and slightly soluble in water. Cyclodextrins are widely used to improve the physicochemical and pharmaceutical properties such as solubility, stability, and bioavailability of poorly soluble drug molecules.Cyclodextrins can molecularly encapsulate various drugs into their hydrophobic cavity without forming any covalent bonds. Cyclodextrin (CDs), especially ß-Cyclodextrin (ß-CD), are widely used in the pharmaceutical field due to its ability to stabilize drug molecules and taste masking purposes. The phase solubility study was performed according to the method of Higuchi and Connors by adding the fexofenadine hydrochloride in excess to different concentrations of cyclodextrin solutions. Phase solubility study records show that the stability constant and complex stoichiometry of FFN-CD complexes increases linearly with CD concentration. Also, an increase in the concentration of β-cyclodextrin leads to an increase in the aqueous solubility of FFN. Complexes were analyzed by UV-VIS spectroscopy using the calibration curve of FFN. Also, UV-VIS spectra indicate a bathochromic shift which proves that complex formation has occurred.Solid inclusion complexes of fexofenadine/β-cyclodextrin and its derivatives were prepared at the molar ratios of 1:1 by the physical mixing method. Characterization of the complexes was performed by using infrared spectroscopy. 

M. Salihović, M. Pazalja, A. Sapcanin, Biljana P. Dojčinović, S. Špirtović-Halilović

The content of macro- and microelements in dry samples of mushrooms of the species Macrolepiota procera, Boletus edulis and Cantharellus cibarius, collected at different areas in Bosnia and Herzegovina, was determined using the ICP-OES method (inductively coupled plasma optical emission spectrometry). Of the macroelements, K is the most represented, followed by S, P, Mg, and the least represented Ca and Na. Zn is the most represented of the essential microelements, followed by Fe, Se, Cu, Mn and Co. Al is the most abundant of the other trace elements followed by Ni and Cr. Of the toxic metals, the most represented is Cd, followed by Pb and As. There are differences in the concentration of micro- and macroelements in the mushrooms analysed, depending on the area from which they were collected because natural geology and geochemistry influence the content of macro- and microelements in wild edible mushrooms. The results show that the analysed mushrooms can be considered a good source of essential elements. The study also assessed potential health risks of heavy metals and the target hazard quotient (THQ) for As, Cd, Pb, Cu, Zn, Ni and Cr in the analysed mushrooms was lower than the safe level. The carcinogenic risk index revealed that Cd and Ni are the most prevalent pollutants in the mushrooms studied.  

M. Salihović, M. Pazalja, Selma Špirtović Halilović, E. Veljović, I. Mahmutović-Dizdarević, S. Roca, I. Novaković, S. Trifunović

Many species of wild mushrooms are used as a delicacy in the diet, but data on their nutritional value and the effects of their storage on nutritional values are rare. The aim of this study was to determine the content of Free Amino Acids (FAAs), total carbohydrates, vitamin C, and total anthocyanins in six wild mushroom species collected in Bosnia and Herzegovina. Results showed that the drying of mushrooms does not have much influence on the presence of essential and non-essential amino acids. Mushrooms are an excellent source of amino acids whether they are fresh or dry. The total carbohydrate content varied between 12.25-62.75 mg g-1 for fresh mushroom extracts and 40.98-167.24 mg g-1 for dry mushroom extracts. The total carbohydrate content in dry mushrooms is significantly higher than in extracts of fresh mushrooms. The vitamin C content of mushrooms varied between 0.02-1.95 mg g-1 for fresh mushrooms and 0.0-0.63 mg g-1 for dry mushrooms. A lower vitamin C content was found in dry mushrooms, which can be affected by the method of drying mushrooms. The total anthocyanins content varied between 0.39-0.66 mg CGE mL-1 for fresh mushroom extracts and 0.10-0.19 mg CGE mL-1 for dry mushroom extracts. Lower total anthocyanins content was found in dry mushroom extracts, probably due to the destruction of anthocyanins by drying. Our research shows that selected wild edible mushrooms, fresh and dry, have considerable nutritional potential. However, further research is needed on both other nutrients and anti-nutrients in these mushrooms to support their nutritional dominance.

U. Glamočlija, S. Špirtović-Halilović, M. Salihović, I. Turel, Jakob Kljun, E. Veljović, S. Zukić, D. Završnik

Using X-ray single crystal diffraction, the crystal structures of biologically active benzoxazole derivatives were determined. DFT calculation was performed with standard 6-31G*(d), 6-31G** and 6-31+G* basis set to analyze the molecular geometry and compare with experimentally obtained X-ray crystal data of compounds. The calculated HOMO-LUMO energy gap in compound 2 (2-(2-hydroxynaphtalen-1-yl)-4-methyl-7-isopropyl-1,3-benzoxazol-5-ol) is 3.80 eV and this small gap value indicates that compound 2 is chemically more reactive compared to compounds 1 (4-methyl-2-phenyl-7-isopropyl-1,3-benzoxazol-5-ol) and 3 (2-(4-chlorophenyl)-4-methyl-7-isopropyl-1,3-benzoxazol-5-ol). The crystal structures are stabilized by both intra- and intermolecular hydrogen bonds in which an intermolecular O-H⋅⋅⋅N hydrogen bond generates N3 and O7 chain motif in compounds 1, 2, and 3, respectively. The calculated bond lengths and bond angles of all three compounds are remarkably close to the experimental values obtained by X-ray single crystal diffraction.

S. Špirtović-Halilović, A. Osmanović, D. Završnik, Aida Selmanagić, Selma Škrbo, Nihada Škrijelj, S. Trifunović, S. Roca et al.

Four 4-hydroxycoumarin derivatives were synthesized and the structure was confirmed by NMR spectroscopy and Mass spectrometry. Tested compounds have shown significant antimicrobial activity against Bacillus subtilis subsp. spizizenii, Bacillus cereus, Staphylococcus aureus, and Staphylococcus epidermidis, and the effect of more halogens on the benzene nucleus, as well as the combination of halogen and alkyl groups, on the antimicrobial activity, was investigated. According to the docking study, these compounds can operate simultaneously on two enzymes, amylase and gyrase (1BAG and 1KZN), which are known to play an important role in bacterial life. Obtained docking study parameters for tested compounds showed an association with the in vitro results of the antimicrobial activity of these compounds. In silico tests of molecular properties of the tested compounds showed that the compounds met Lipinski's rule of five. In this paper, the ADME parameters of tested compounds were also calculated: Caco2 (in vitro Caco2 cell permeability), HIA (human intestinal absorption), MDCK (in vitro Mandin Darby Canine Kidney (MDCK) cell permeability), TPSA (topological polar surface area), etc.

Rutin is quercetin heteroside widely present in plants that exhibit many health-beneficial effects, such as strengthening the capillary walls, reducing the harmful effects of LDL cholesterol, and reducing the risk of cardiovascular diseases. Rutin was determined from three <i>Allium</i> species (<i>A. cepa</i>, <i>A. sativum</i>, and <i>A. ursinum</i>) collected in Bosnia and Herzegovina by the HPLC method associated with electrochemical detection. The analysis was performed from methanol extracts of bulb and leaf of garlic, bulb and leaf of onion, and leaves of wood garlic. Rutin was present in all of the examined samples. The highest rutin content was found in garlic leaves (0.78 ± 0.09 mg g<sup>–1</sup>), and the lowest in onion bulbs (0.04 ± 0.10 mg g<sup>–1</sup>). The contents of rutin were higher in leaf samples, suggesting that leaves of onion and garlic are recommended as a better natural source of this glycoside.

E. Veljović, S. Špirtović-Halilović, Samija Muratović, A. Osmanović, S. Haverić, A. Haverić, M. Hadzic, M. Salihović et al.

Abstract 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’ position of the phenyl ring showed the best inhibitory activity towards HeLa and A549 tumor cells with IC50 of 0.7 and 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.

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