Procena antikancerogene aktivnosti novih organokalaj(IV) jedinjenja koja sadrže derivate 2-propanske kiseline

Two novel organotin(IV) compounds containing 2-propanoic acid derivatives were synthesized and characterized by standard spectroscopic methods. In vitro antiproliferative activity of these complexes was investigated versus four tumor cell lines: PC3 (prostate), HT-29 (colon), MCF-7 (breast) and HepG2 (hepatic) using MTT and CV assays. The results have shown that that synthesized complexes exhibit remarkable anticancer activity toward all tested cell lines with 54 to 113 fold higher activity than the reference compound cisplatin. The obtained promising results indicate the necessity for further in vitro/in vivo research with the aim to investigate the mechanism of action of these potencial antitumor agents.Dva nova organokalaj(IV) jedinjenja, koja sadrže derivate 2-propanske kiseline, sintetisana su i okarakterisana pomoću standardnih spektroskopskih metoda. In vitro antiproliferativna aktivnost ovih jedinjenja ispitana je prema četiri tumorske ćelijske linije: PC3 (prostata), HT-29 (debelo crevo), MCF-7 (dojka) i HepG2 (jetra) pomoću MTT and CV testova. Rezultati ispitivanja ukazuju da sintetisana jedinjenja ispoljavaju izvanrednu antikancerogenu aktivnost prema svim ispitanim ćelijskim linijama i njihova aktivnost je od 54 do 113 puta veća od aktivnosti referentne supstance, cisplatine. Dobijeni rezultati ukazuju na neophodnost daljih in vitro/in vivo istraživanja sa ciljem ispitivanja mehanizma delovanja ovih potencijalnih antitumorskih agenasa

Procena antikancerogene aktivnosti novih organokalaj(IV) jedinjenja koja sadrže derivate 2-propanske kiseline

Two novel organotin(IV) compounds containing 2-propanoic acid derivatives were synthesized and characterized by standard spectroscopic methods. In vitro antiproliferative activity of these complexes was investigated versus four tumor cell lines: PC3 (prostate), HT-29 (colon), MCF-7 (breast) and HepG2 (hepatic) using MTT and CV assays. The results have shown that that synthesized complexes exhibit remarkable anticancer activity toward all tested cell lines with 54 to 113 fold higher activity than the reference compound cisplatin. The obtained promising results indicate the necessity for further in vitro/in vivo research with the aim to investigate the mechanism of action of these potencial antitumor agents.Dva nova organokalaj(IV) jedinjenja, koja sadrže derivate 2-propanske kiseline, sintetisana su i okarakterisana pomoću standardnih spektroskopskih metoda. In vitro antiproliferativna aktivnost ovih jedinjenja ispitana je prema četiri tumorske ćelijske linije: PC3 (prostata), HT-29 (debelo crevo), MCF-7 (dojka) i HepG2 (jetra) pomoću MTT and CV testova. Rezultati ispitivanja ukazuju da sintetisana jedinjenja ispoljavaju izvanrednu antikancerogenu aktivnost prema svim ispitanim ćelijskim linijama i njihova aktivnost je od 54 do 113 puta veća od aktivnosti referentne supstance, cisplatine. Dobijeni rezultati ukazuju na neophodnost daljih in vitro/in vivo istraživanja sa ciljem ispitivanja mehanizma delovanja ovih potencijalnih antitumorskih agenasa

Supplementary data for the article: Pešić, M. B.; Milinčić, D. D.; Kostić, A.; Stanisavljević, N. S.; Vukotić, G. N.; Kojić, M. O.; Gašić, U. M.; Barać, M. B.; Stanojević, S. P.; Popović, D. A.; et al. In Vitro Digestion of Meat- and Cereal-Based Food Matrix Enriched with Grape Extracts: How Are Polyphenol Composition, Bioaccessibility and Antioxidant Activity Affected? Food Chem. 2019, 284, 28–44. https://doi.org/10.1016/j.foodchem.2019.01.107

Supplementary material for: [https://doi.org/10.1016/j.foodchem.2019.01.107]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/2843]Related to accepted version: [http://cherry.chem.bg.ac.rs/handle/123456789/2867

Synthesis, characterization and in vitro biological evaluation of novel organotin(IV) compounds with derivatives of 2-(5-arylidene-2,4- dioxothiazolidin-3-yl)propanoic acid

Two novel triphenyltin(IV) compounds, [Ph3SnL1] (L1 = 2-(5-(4-fluorobenzylidene)-2,4-dioxotetrahydrothiazole-3-yl)propanoate (1)) and [Ph3SnL2] (L2 = 2-(5-(5-methyl-2-furfurylidene)-2,4-dioxotetrahydrothiazole-3-yl)propanoate (2)) were synthesized and characterized by FT-IR, (1H and 13C) NMR spectroscopy,mass spectrometry, and elemental microanalysis. The in vitro anticancer activity of the synthesized organotin(IV)compounds was determined against four tumor cell lines: PC-3 (prostate), HT-29 (colon), MCF-7 (breast), andHepG2 (hepatic) using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-12 diphenyltetrazolium bromide) and CV (crystalviolet) assays. The IC50 values are found to be in the range from 0.11 to 0.50 μM. Compound 1 exhibits thehighest activity toward PC-3 cells (IC50 = 0.115 } 0.009 μM; CV assay). The tin and platinum uptake in PC-3cells showed a threefold lower uptake of tin in comparison to platinum (as cisplatin). Together with its higheractivity this indicates a much higher cell inhibition potential of the tin compounds (calculated to ca. 50 to 100times). Morphological analysis suggested that the compounds induce apoptosis in PC-3 cells, and flow cytometryanalysis revealed that 1 and 2 induce autophagy as well as NO (nitric oxide) production.This is the peer-reviewed version of the article: Nebojša Đ. Pantelić, Bojana B. Zmejkovski, Bojan Božić, Biljana Dojčinović, Nebojša R. Banjac, Ludger A. Wessjohann, Goran N. Kaluđerović, Synthesis, characterization and in vitro biological evaluation of novel organotin(IV) compounds with derivatives of 2-(5-arylidene-2,4- dioxothiazolidin-3-yl)propanoic acid, Journal of Inorganic Biochemistry, 2020, 212, 111207, doi: [https://doi.org/10.1016/j.jinorgbio.2020.111207]The published version: [http://cer.ihtm.bg.ac.rs/handle/123456789/3653

Synthesis, structure and solvatochromism of 5-methyl-5-(3- or 4-substituted phenyl)hydantoins

Several 5-methyl-5-(3- or 4-substituted phenyl)hydantoins were prepared and their ultraviolet absorption spectra were recorded in the region 200–400 nm in twelve solvents of different polarity. The effect of solvent dipo¬larity/polarizability and solvent/solute hydrogen bonding interactions were analyzed by means of the linear solvation energy relationship (LSER) concept proposed by Kamlet and Taft. The lipophilic activity of the investigated hydantoins was estimated by calculation of log P values with Advanced Chemistry Development Software. The calculated values of log P were correlated with the contribution of hydrogen bond donor–solvent interactions. By employing the thus obtained linear dependence, the pharmacological activity of the studied hydantoin derivatives is discussed

In Vitro Evaluation of Antiproliferative Properties of Novel Organotin(IV) Carboxylate Compounds with Propanoic Acid Derivatives on a Panel of Human Cancer Cell Lines

The synthesis of novel triphenyltin(IV) compounds, Ph3SnLn (n = 1–3), with oxaprozin (3-(4,5-diphenyloxazol-2-yl)propanoic acid), HL1, and the new propanoic acid derivatives 3-(4,5bis(4-methoxylphenyl)oxazol-2-yl)propanoic acid, HL2, and 3-(2,5-dioxo-4,4-diphenylimidazolidin1-yl)propanoic acid, HL3, has been performed. The ligands represent commercial drugs or their derivatives and the tin complexes have been characterized by standard analytical methods. The in vitro antiproliferative activity of both ligands and organotin(IV) compounds has been evaluated on the following tumour cell lines: human prostate cancer (PC-3), human colorectal adenocarcinoma (HT29), breast cancer (MCF-7), and hepatocellular cancer (HepG2), as well as on normal mouse embryonic fibroblast cells (NIH3T3) with the aid of MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-12 diphenyltetrazolium bromide) and CV (crystal violet) assays. Contrary to the inactive ligand precursors, all organotin(IV) carboxylates showed very good activity with IC50 values ranging from 0.100 to 0.758 µM. According to the CV assay (IC50 = 0.218 ± 0.025 µM), complex Ph3SnL1 demonstrated the highest cytotoxicity against the caspase 3 deficient MCF-7 cell line. Inductively coupled plasma mass spectrometry (ICP-MS) analysis indicated a two-fold lower concentration of tin in MCF-7 cells in comparison to platinum. To investigate the mechanism of action of the compound Ph3SnL1 on MCF-7 cells, morphological, autophagy and cell cycle analysis, as well as the activation of caspase and ROS/RNS and NO production, has been performed. Results suggest that Ph3SnL1 induces caspase-independent apoptosis in MCF-7 cells

Buckwheat and quinoa seeds as supplements in wheat bread production

The aim of this work was to compare the nutritional characteristics of wheat bread with the bread produced of wheat flour supplemented with quinoa and buckwheat seeds. Bread making properties of these blends were analyzed in order to investigate their ability to make moulded bread. Quinoa (Chenopodium quinoa Will.) and buckwheat seeds were grown in the vicinity of Belgrade, Serbia. The addition of pseudocereal seeds (at levels of 30% and 40%) and a selected technological process, which included hydrothermal preparation of supplements, resulted with a valuable effect on nutritive value of breads. In comparison with the wheat bread that was used as control sample, the protein increase of 2% and the increase of crude fiber content at around 0.5% in 30% supplemented breads were registered. Furthermore, the incorporation of both seeds mixture at the level of 40%, increased the content of protein for 2.5% and fiber content for 0.4%. In regard to the starch, fat, and ash contents there were no major differences. The investigated breads were nutritionally superior to the wheat bread. Chemical composition of the selected seeds was also investigated. The results showed that the blends containing either 30% or 40% of selected seeds expressed high potential for the production of molded breads, as new baking products with enhanced nutritional composition. The applied technological procedure was modified in such way that for all blended combination of supplements it changed rheological properties of dough. Furthermore, it resulted in a good volume of breads with excellent sensory properties of aroma-odor and taste

Solvent effects on the absorption spectra of potentially pharmacologically active 5-alkyl-5-arylhydantoins: A structure-property relationship study

To obtain an insight into the interactions of potential anticonvulsant drugs with their surrounding, two series of 5-methyl-5-aryl- and 5-ethyl-5-arylhydantoins were synthesized and their absorption spectra were recorded in the region from 200 to 400 nm in a set of selected solvents. The effects of solvent dipolarity/polarizability and solvent-solute hydrogen bonding interactions on the absorption maxima shifts were analyzed by means of the linear solvation energy relationship (LSER) concept of Kamlet and Taft. The ratio of the contributions of specific and nonspecific solvent-solute interactions were correlated with the corresponding ADME properties of the studied compounds. The correlation equations were combined with different physicochemical parameters to generate new equations, which demonstrate the reasonable relationships between solvent-solute interactions and the structure-activity parameters. [Projekat Ministarstva nauke Republike Srbije, br. 172013

In vitro digestion of meat- and cereal-based food matrix enriched with grape extracts: How are polyphenol composition, bioaccessibility and antioxidant activity affected?

The aim of this study was to evaluate the effect of enriching a complex food matrix (FM) with grape extracts on polyphenol content, composition, bioaccessibility and antioxidant activity during digestion. The grape extracts and FM were separately tested under the same conditions as controls. The FM by itself contains a significant amount of phenolic acids and flavonols, influencing the final recovery of polyphenols from grape extracts. The FM significantly increased the total recovery of polyphenols after digestion of grape seed extracts compared to those digested without the FM; however, a low recovery of proantocyanidins and total flavonoids was observed. Digestive fluids and FM compounds significantly increased the total polyphenol content of grape digests and significantly contributed to their ABTS(center dot+) scavenging activity and ferrous-ion-chelating capacity. The present study suggested that enrichment of meat-and cereal-based products with grape polyphenol extracts could be a good strategy to formulate a healthier diet.This is the peer-reviewed version of the article: [https://imagine.imgge.bg.ac.rs/handle/123456789/1609][https://www.sciencedirect.com/science/article/abs/pii/S030881461930175X?via%3Dihub

Quntum mechanical and spectroscopic (FT-IR, C-13, H-1 NMR and UV) investigations of potent antiepileptic drug 1-(4-chloro-phenyl)-3-phenyl-succinimide

This study represents an integrated approach towards understanding the vibrational, electronic, NMR, and structural aspects, and reactivity of 1-(4-chloro-phenyl)-3-phenyl-succinimide (CPPS). A detailed interpretation of the FT-IR, UV and NMR spectra were reported. The equilibrium geometry, bonding features, and harmonic vibrational frequencies have been investigated with the help of density functional theory (DFT) B3LYP method using 6-31G(d,p) and 6-311++G(d,p) basis set. The scaled theoretical wave-number showed very good agreement with the experimental values. The H-1 and C-13 nuclear magnetic resonance (NMR) chemical shifts of the molecule were calculated by the Gauge-Invariant Atomic Orbital (GIAO) method. Stability of the molecule, arising from hyperconjugative interactions and charge delocalization, has been analyzed using Natural Bond Orbital (NBO) analysis. The results show that ED in the sigma* and pi* antibonding orbitals and second order delocalization energies E(2) confirm the occurrence of intramolecular charge transfer (ICT) within the molecule. UV-Vis spectrum of the compound was recorded and the electronic properties, such as HOMO and LUMO energies, were calculated by Time-Dependent (TD-DFT) approach. To estimate chemical reactivity of the molecule, the molecular electrostatic potential (MEP) surface map is calculated for the optimized geometry of the molecule