Nano-QSAR: Model of mutagenicity of fullerene as a mathematical function of different conditions

The experimental data on the bacterial reverse mutation test (under various conditions) on C60 nanoparticles for the cases (i) TA100, and (ii) WP2uvrA/pkM101 are examined as endpoints. By means of the optimal descriptors calculated with the Monte Carlo method a mathematical model of these endpoints has been built up. The models are a mathematical function of eclectic data such as (i) dose (g/plate); (ii) metabolic activation (i.e. with mix S9 or without mix S9); and (iii) illumination (i.e. darkness or irradiation). The eclectic data on different conditions were represented by so-called quasi-SMILES. In contrast to the traditional SMILES which are representation of molecular structure, the quasi-SMILES are representation of conditions by sequence of symbols. The calculations were carried out with the CORAL software, available on the Internet at http://www.insilico.eu/coral. The main idea of the suggested descriptors is the accumulation of all available eclectic information in the role of logical and digital basis for building up a model. The computational experiments have shown that the described approach can be a tool to build up models of mutagenicity of fullerene under different conditions

Supplementary data for article: Veselinović, J. B.; Kocić, G. M.; Pavic, A.; Nikodinovic-Runic, J.; Senerovic, L.; Nikolić, G. M.; Veselinović, A. M. Selected 4-Phenyl Hydroxycoumarins: In Vitro Cytotoxicity, Teratogenic Effect on Zebrafish (Danio Rerio) Embryos and Molecular Docking Study. Chemico-Biological Interactions 2015, 231, 167–174. https://doi.org/10.1016/j.cbi.2015.02.011

Supplementary material for: [https://doi.org/10.1016/j.cbi.2015.02.011]Related to published version: [http://cherry.chem.bg.ac.rs/handle/123456789/1699

The influence of divalent diamagnetic metal ions on vicinal trihydroxy phenolic compounds autoxidation in aqueous solutions

In this dissertation the influence of divalent diamagnetic metal ions (Mg(II), Ca(II), Sr(II), Ba(II), Zn(II), Cd(II) and Pb(II)) on vicinal trihydroxy phenolic compounds autoxidation in aqueous solutions was examined. Autoxidation processes of pyrogallol (the simplest compound with appropriate structure), gallic acid and ethyl gallate were studied with the application of UV/Vis spectrophotometry with chemometric data processing, EPR spectroscopy, High-performance liquid chromatography (HPLC) and Mass spectrometry (ESI-MS). It was determined that pH value of solution and presence and type of diamagentic metal ions have great influence on investigated compounds autoxidation processes rates and mechanism. With the aid of applied techniques the structures of transition free radical species and stable autoxidation processes products were determined. Obtained results enabled better understanding of investigated compounds autoxidation processes which is of great importance since gallic acid is found in many plants, while ethyl gallate is used as an antioxidant in food

The influence of divalent diamagnetic metal ions on vicinal trihydroxy phenolic compounds autoxidation in aqueous solutions

In this dissertation the influence of divalent diamagnetic metal ions (Mg(II), Ca(II), Sr(II), Ba(II), Zn(II), Cd(II) and Pb(II)) on vicinal trihydroxy phenolic compounds autoxidation in aqueous solutions was examined. Autoxidation processes of pyrogallol (the simplest compound with appropriate structure), gallic acid and ethyl gallate were studied with the application of UV/Vis spectrophotometry with chemometric data processing, EPR spectroscopy, High-performance liquid chromatography (HPLC) and Mass spectrometry (ESI-MS). It was determined that pH value of solution and presence and type of diamagentic metal ions have great influence on investigated compounds autoxidation processes rates and mechanism. With the aid of applied techniques the structures of transition free radical species and stable autoxidation processes products were determined. Obtained results enabled better understanding of investigated compounds autoxidation processes which is of great importance since gallic acid is found in many plants, while ethyl gallate is used as an antioxidant in food

Influence of Zn(II) Ion on the Autoxidation of Pyrogallol and Gallic Acid in Weakly Acidic Aqueous Solutions / Uticaj Zn(II) jona na autooksidaciju pirogalola i galne kiseline u slabo kiselim vodenim rastvorima

Fenolna jedinjenja sa strukturom pirogalola su široko rasprostranjena u prirodi i mogu da imaju značajan uticaj na ljudsko zdravlje. Kako je pokazano da Zn(II) jon ima sposobnost da pojačava neke biološke aktivnosti prirodnih fenolnih jedinjenja sa strukturom pirogalola, odlučili smo da ispitamo njegov uticaj na autooksidaciju pirogalola i galne kiseline u slabo kiselim vodenim rastvorima

Antioxidant properties of selected 4-phenyl hydroxycoumarins: Integrated in vitro and computational studies

A study on the structure-activity relationship of three hydroxy 4-phenyl coumarins, carried out by employing a series of different chemical cell-free tests is presented. Different assays involving one redox reaction with the oxidant (DPPH, ABTS, FRAP and CUPRAC) were employed. Further, the measurement of inhibition of oxidative degradation, such as lipid peroxidation, was used to define compound antioxidant activity. Our results confirm the good antioxidant activity of the 7,8-dihydroxy-4-phenyl coumarin and moderate antioxidant activity of 5,7-dihydroxy-4-phenyl coumarin. In this work, quantum chemical calculations based on density functional theory have been employed at B3LYP/6-311++G(d,p) level of theory to study the influence of number and position of hydroxyl groups in coumarin molecules on antioxidant activity. Calculated values for HOMO and LUMO energies, energy gap, stabilization energies and spin density distribution confirmed experimental results and were used for SAR definition. For determination of reaction mechanism in gas phase and selected solvents bond dissociation enthalpy, adiabatic ionization potential, proton dissociation enthalpy, proton affinity, electron transfer enthalpy and gas phase acidity have been calculated. Hydrogen Atom Transfer mechanism in vacuum and Single-Electron Transfer followed by the Proton Transfer mechanism in other studied systems are most probable free radical scavenging pathways. On the basis of these findings, these hydroxy 4-phenyl coumarins may be considered as potential therapeutic candidates for pathological conditions characterized by free radical overproduction

Selected 4-phenyl hydroxycoumarins: In vitro cytotoxicity, teratogenic effect on zebrafish (Danio rerio) embryos and molecular docking study

A study of structure cytotoxic-activity relationship of three hydroxy 4-phenyl-coumarins and basic coumarin molecule against two human cell lines (MRC5 fibroblasts and A375 melanoma cells) is presented. Of all investigated compounds the highest cytotoxic activity in both cell lines was determined for 7,8-dihydroxy-4-phenyl coumarin. SAR studies revealed the influence of phenyl group and hydroxyl group's number and position on cytotoxic activity. In addition, to get an insight about their binding preferences at the active site of the receptor (catalytic subunit of cAMP-dependent protein kinase) molecular docking studies were performed. Docking studies suggest that 4-phenyl hydroxycoumarins are potent cAMP-dependent protein kinase inhibitors, better than their analogs without phenyl group. The teratogenic potential was assessed in zebrafish embryo toxicity test and results showed that 4-phenyl dihydroxycoumarins were more while 7-hydroxy-4-phenyl coumarin was less embryo toxic in comparison to coumarin. In order to examine selected 4-phenyl hydroxycoumarins as a new lead compounds the druglikeness of selected 4-phenyl hydroxycoumarins was estimated by using Lipinski's "rule of five". All selected 4-phenyl hydroxycoumarins proved to have satisfying pharmacokinetic profile.Supplementary material: [http://cherry.chem.bg.ac.rs/handle/123456789/3410

Selected 4-phenyl hydroxycoumarins: In vitro cytotoxicity, teratogenic effect on zebrafish (Danio rerio) embryos and molecular docking study

A study of structure cytotoxic-activity relationship of three hydroxy 4-phenyl-coumarins and basic coumarin molecule against two human cell lines (MRC5 fibroblasts and A375 melanoma cells) is presented. Of all investigated compounds the highest cytotoxic activity in both cell lines was determined for 7,8-dihydroxy-4-phenyl coumarin. SAR studies revealed the influence of phenyl group and hydroxyl group's number and position on cytotoxic activity. In addition, to get an insight about their binding preferences at the active site of the receptor (catalytic subunit of cAMP-dependent protein kinase) molecular docking studies were performed. Docking studies suggest that 4-phenyl hydroxycoumarins are potent cAMP-dependent protein kinase inhibitors, better than their analogs without phenyl group. The teratogenic potential was assessed in zebrafish embryo toxicity test and results showed that 4-phenyl dihydroxycoumarins were more while 7-hydroxy-4-phenyl coumarin was less embryo toxic in comparison to coumarin. In order to examine selected 4-phenyl hydroxycoumarins as a new lead compounds the druglikeness of selected 4-phenyl hydroxycoumarins was estimated by using Lipinski's "rule of five". All selected 4-phenyl hydroxycoumarins proved to have satisfying pharmacokinetic profile

QSAR modeling of dihydrofolate reductase inhibitors as a therapeutic target for multiresistant bacteria

Antibacterial resistance is a growing public health threat of major concern around the world so development of new therapeutic approaches to prevent bacterial multidrug resistance has become a primary consideration for medicinal chemistry research. QSAR models for the dihydrofolate reductase inhibition with 2,4-diamino-5-(substituted-benzyle)-pyramidine derivatives were developed with further computer-aided design of new derivatives with desired activity. The Monte Carlo method has been used as a computational tool for QSAR modeling. For the representation of molecular structure and optimal descriptor calculation, the simplified molecular input line entry system (SMILES) together with the molecular graph (hydrogen-suppressed graph-HSG, hydrogen-filled graph-HFG, and the graph of atomic orbitals-GAO) was used. One-variable models have been calculated for one data split into training, test, and validation set. The impact of Morgan's extended connectivity index on built QSAR models and outliers was determined. Statistical parameters for the best QSAR model are satisfying. Structural indicators (molecular fragments) responsible for the increase and the decrease of the stated activity are defined, and with the application of defined structural alerts, the computer-aided design of new derivatives with desired activity is presented. Computational experiments presented and applied in this research can satisfactorily predict desired endpoint and can be used further for computer-aided antibacterial drug design

Potent anti-melanogenic activity and favorable toxicity profile of selected 4-phenyl hydroxycoumarins in the zebrafish model and the computational molecular modeling studies

7-Hydroxy-4-phenylcoumarin (7C) and 5,7-dihydroxy-4-phenylcoumarin (5,7C) have been evaluated as potential anti-melanogenic agents in the zebrafish (Danio rerio) model in comparison to commercially utilized depigmenting agents hydroquinone and kojic acid. 7C and 5,7C decreased the body pigmentation at 5 mu g/mL, while did not affect the embryos development and survival at doses lt = 50 mu g/mL and lt = 25 mu g/mL. Unlike hydroquinone and kojic acid, 4-phenyl hydroxycoumarins were no melanocytotoxic, showed no cardiotoxic side effects, neither caused neutropenia in zebrafish embryos, suggesting these compounds may present novel skin-whitening agents with improved pharmacological properties. Inhibition of tyrosinase was identified as the possible mode of anti-melanogenic action. Molecular docking studies using the homology model of human tyrosinase as well as adenylate cyclase revealed excellent correlation with experimentally obtained results