scholarly journals Lomefloxacin—Occurrence in the German River Erft, Its Photo-Induced Elimination, and Assessment of Ecotoxicity

2020 ◽  
Vol 2 (1) ◽  
pp. 74-90 ◽  
Author(s):  
Melanie Voigt ◽  
Benjamin Hentschel ◽  
Nina Theiss ◽  
Christina Savelsberg ◽  
Indra Bartels ◽  
...  
Keyword(s):  
Irradiation Time ◽  
Transformation Products ◽  
Quantitative Structure Activity Relationship ◽  
The Novel ◽  
Qsar Analysis ◽  
Water Matrix ◽  
Kinetic Rate Constants ◽  
Time Required ◽  
Far Ultraviolet ◽  
Uvc Radiation

Pharmaceuticals in waters represent a worldwide problem of today. Advanced oxidation processes (AOPs) are being researched for elimination of the ecological hazard. Among the substances, the fluoroquinolone antibiotic lomefloxacin was selected for investigation in this study. Lomefloxacin (LOM) was found in the German river Erft. Near and far ultraviolet (UVA, UVC) radiation were used as AOPs and compared for efficiency depending on pH, water matrix, and catalysts. Chemical kinetics description revealed that UVC at pH 8–9 led to the fastest degradation of LOM. The catalysts hydrogen peroxide and titanium dioxide had only limited influence on the degradation rate. Seven novel transformation products were structurally identified by high-resolution higher-order mass spectrometry. Ecotoxicity of the novel and known compounds was assessed by quantitative structure-activity relationship (QSAR) analysis. In addition, irradiation time dependent minimal, and half-maximal inhibitory concentrations (MIC, IC50) of LOM solutions were determined and suggested as ecotoxicological hazard indicators. From MIC and kinetic rate constants, the irradiation time required for compound and activity removal could be predicted.

scholarly journals Metoprolol and Its Degradation and Transformation Products Using AOPs—Assessment of Aquatic Ecotoxicity Using QSAR

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3102
Author(s):  
Melanie Voigt ◽  
Indra Bartels ◽  
Dorothee Schmiemann ◽  
Lars Votel ◽  
Kerstin Hoffmann-Jacobsen ◽  
...  
Keyword(s):  
Hydrogen Peroxide ◽  
High Performance ◽  
Degradation Products ◽  
Sewage Treatment ◽  
Transformation Products ◽  
Quantitative Structure Activity Relationship ◽  
Secondary Products ◽  
Structural Isomers ◽  
Qsar Analysis ◽  
Accelerated Degradation

Pharmaceuticals are found in waterbodies worldwide. Conventional sewage treatment plants are often not able to eliminate these micropollutants. Hence, Advanced Oxidation Processes (AOPs) have been heavily investigated. Here, metoprolol is exposed to UV irradiation, hydrogen peroxide, and ozonation. Degradation was analyzed using chemical kinetics both for initial and secondary products. Photo-induced irradiation enhanced by hydrogen peroxide addition accelerated degradation more than ozonation, leading to complete elimination. Degradation and transformation products were identified by high-performance liquid-chromatography coupled to high-resolution higher-order mass spectrometry. The proposed structures allowed to apply Quantitative Structure-Activity Relationship (QSAR) analysis to predict ecotoxicity. Degradation products were generally associated with a lower ecotoxicological hazard to the aquatic environment according to OECD QSAR toolbox and VEGA. Comparison of potential structural isomers suggested forecasts may become more reliable with larger databases in the future.

In vitro Cytotoxicity and Genotoxicity Analysis of Ten Tannery Chemicals Using SOS/umu Tests and High-content In vitro Micronucleus Tests

2018 ◽  
Vol 21 (4) ◽  
pp. 262-270 ◽  
Author(s):  
Zehao Huang ◽  
Na Li ◽  
Kaifeng Rao ◽  
Cuiting Liu ◽  
Zijian Wang ◽  
...  
Keyword(s):  
Micronucleus Test ◽  
A549 Cells ◽  
Quantitative Structure Activity Relationship ◽  
In Vitro Cytotoxicity ◽  
Cytotoxic Effects ◽  
Qsar Analysis ◽  
Cell Assays ◽  
Micronucleus Tests ◽  
Damaging Effects

Background: More than 2,000 chemicals have been used in the tannery industry. Although some tannery chemicals have been reported to have harmful effects on both human health and the environment, only a few have been subjected to genotoxicity and cytotoxicity evaluations. Objective: This study focused on cytotoxicity and genotoxicity of ten tannery chemicals widely used in China. Materials and Methods: DNA-damaging effects were measured using the SOS/umu test with Salmonella typhimurium TA1535/pSK1002. Chromosome-damaging and cytotoxic effects were determined with the high-content in vitro Micronucleus test (MN test) using the human-derived cell lines MGC-803 and A549. Conclusion: The cytotoxicity of the ten tannery chemicals differed somewhat between the two cell assays, with A549 cells being more sensitive than MGC-803 cells. None of the chemicals induced DNA damage before metabolism, but one was found to have DNA-damaging effects on metabolism. Four of the chemicals, DY64, SB1, DB71 and RR120, were found to have chromosome-damaging effects. A Quantitative Structure-Activity Relationship (QSAR) analysis indicated that one structural feature favouring chemical genotoxicity, Hacceptor-path3-Hacceptor, may contribute to the chromosome-damaging effects of the four MN-test-positive chemicals.

Synthesis of New N1Arylpiperazine Substituted Xanthine Derivatives and Evaluation of their Antioxidant and Cytotoxic Effects

2019 ◽  
Vol 19 (4) ◽  
pp. 528-537 ◽  
Author(s):  
Lily Andonova ◽  
Iva Valkova ◽  
Dimitrina Zheleva-Dimitrova ◽  
Maya Georgieva ◽  
Georgi Momekov ◽  
...  
Keyword(s):  
Antioxidant Activity ◽  
Structural Parameters ◽  
Leukemia Cell ◽  
Quantitative Structure Activity Relationship ◽  
Cytotoxic Effects ◽  
Qsar Analysis ◽  
Xanthine Derivatives ◽  
Human T Cell ◽  
Human Acute Myeloid Leukemia ◽  
Dye Reduction

Background: Cancer is one of the leading causes of morbidity and mortality worldwide, with approximately 14 million new cases in 2012, with most of the clinically used drugs being ineffective. Methylxanthines have raised more interest in research on modifying their structure because of their diverse biological activity. In addition, the piperazine nucleus is one of the most important heterocycles exhibiting remarkable pharmacological activities. Methods: The structure of the obtained compounds was characterized and elucidated by IR, 1H and 13C NMR and LCMS spectral analysis. The purity of the substances was proven by corresponding melting points and elemental analysis. The antioxidant activity was evaluated by four common methods – DPPH, ABTS, FRAP and lipid peroxidation assay. The cytotoxic effects of the tested series were evaluated using the standard MTT-dye reduction assay on three tumour cell lines. Results: A series of new xanthine derivatives comprising an arylpiperazine moiety at N1 were synthesized. The cytotoxicity against human T-cell leukemia cell SKW-3, human acute myeloid leukemia HL-60 and human Bcell precursor leukemia cell REH was evaluated. The relationship between the structure and citotoxicity of the compounds was investigated by quantitative structure-activity relationship (QSAR) analysis and the important structural parameters were drawn. Conclusion: The highest antioxidant activity was demonstrated by compound 6c. The highest cytotoxic effect was observed for compound 6f. It was found that cytotoxicity against SKW-3 depends on the electron density distribution in the structures. Branching of the molecular skeleton and introduction of heteroatoms like fluorine and sulfur in the structures also significantly improved the antiproliferative activity of the compounds.

scholarly journals Identification of Anti-SARS-CoV-2 Compounds from Food Using QSAR-Based Virtual Screening, Molecular Docking, and Molecular Dynamics Simulation Analysis

2021 ◽  
Vol 14 (4) ◽  
pp. 357
Author(s):  
Magdi E. A. Zaki ◽  
Sami A. Al-Hussain ◽  
Vijay H. Masand ◽  
Siddhartha Akasapu ◽  
Sumit O. Bajaj ◽  
...  
Keyword(s):  
Molecular Dynamics ◽  
Molecular Docking ◽  
Virtual Screening ◽  
Simulation Analysis ◽  
Qsar Model ◽  
Quantitative Structure Activity Relationship ◽  
Dynamics Simulation ◽  
Multilinear Regression ◽  
Qsar Analysis ◽  
Main Protease

Due to the genetic similarity between SARS-CoV-2 and SARS-CoV, the present work endeavored to derive a balanced Quantitative Structure−Activity Relationship (QSAR) model, molecular docking, and molecular dynamics (MD) simulation studies to identify novel molecules having inhibitory potential against the main protease (Mpro) of SARS-CoV-2. The QSAR analysis developed on multivariate GA–MLR (Genetic Algorithm–Multilinear Regression) model with acceptable statistical performance (R2 = 0.898, Q2loo = 0.859, etc.). QSAR analysis attributed the good correlation with different types of atoms like non-ring Carbons and Nitrogens, amide Nitrogen, sp2-hybridized Carbons, etc. Thus, the QSAR model has a good balance of qualitative and quantitative requirements (balanced QSAR model) and satisfies the Organisation for Economic Co-operation and Development (OECD) guidelines. After that, a QSAR-based virtual screening of 26,467 food compounds and 360 heterocyclic variants of molecule 1 (benzotriazole–indole hybrid molecule) helped to identify promising hits. Furthermore, the molecular docking and molecular dynamics (MD) simulations of Mpro with molecule 1 recognized the structural motifs with significant stability. Molecular docking and QSAR provided consensus and complementary results. The validated analyses are capable of optimizing a drug/lead candidate for better inhibitory activity against the main protease of SARS-CoV-2.

scholarly journals A Fast Retrieval of Cloud Parameters Using a Triplet of Wavelengths of Oxygen Dimer Band around 477 nm

2021 ◽  
Vol 13 (1) ◽  
pp. 152
Author(s):  
Haklim Choi ◽  
Xiong Liu ◽  
Gonzalo Gonzalez Abad ◽  
Jongjin Seo ◽  
Kwang-Mog Lee ◽  
...  
Keyword(s):  
Scattered Light ◽  
Trace Gas ◽  
Retrieval Algorithm ◽  
The Novel ◽  
Cloud Parameters ◽  
Retrieval Scheme ◽  
The Difference ◽  
The Look ◽  
Time Required ◽  
Cloud Top Pressure

Clouds act as a major reflector that changes the amount of sunlight reflected to space. Change in radiance intensity due to the presence of clouds interrupts the retrieval of trace gas or aerosol properties from satellite data. In this paper, we developed a fast and robust algorithm, named the fast cloud retrieval algorithm, using a triplet of wavelengths (469, 477, and 485 nm) of the O2–O2 absorption band around 477 nm (CLDTO4) to derive the cloud information such as cloud top pressure (CTP) and cloud fraction (CF) for the Geostationary Environment Monitoring Spectrometer (GEMS). The novel algorithm is based on the fact that the difference in the optical path through which light passes with regard to the altitude of clouds causes a change in radiance due to the absorption of O2–O2 at the three selected wavelengths. To reduce the time required for algorithm calculations, the look-up table (LUT) method was applied. The LUT was pre-constructed for various conditions of geometry using Vectorized Linearized Discrete Ordinate Radiative Transfer (VLIDORT) to consider the polarization of the scattered light. The GEMS was launched in February 2020, but the observed data of GEMS have not yet been widely released. To evaluate the performance of the algorithm, the retrieved CTP and CF using observational data from the Global Ozone Monitoring Experiment-2 (GOME-2), which cover the spectral range of GEMS, were compared with the results of the Fast Retrieval Scheme for Clouds from the Oxygen A band (FRESCO) algorithm, which is based on the O2 A-band. There was good agreement between the results, despite small discrepancies for low clouds.

Design of Dual COX-2 and 5-LOX Inhibitors with Iron-Chelating Properties Using Structure-Based and Ligand-Based Methods

2021 ◽  
Vol 18 ◽  
Author(s):  
Jelena Bošković ◽  
Dušan Ružić ◽  
Olivera Čudina ◽  
Katarina Nikolic ◽  
Vladimir Dobričić
Keyword(s):  
Molecular Docking ◽  
External Validation ◽  
Three Dimensional ◽  
3D Qsar ◽  
Quantitative Structure Activity Relationship ◽  
Docking Studies ◽  
Qsar Analysis ◽  
In Silico Admet ◽  
Cox 2 ◽  
Lox Inhibitors

Background: Inflammation is common pathogenesis of many diseases progression, such as malignancy, cardiovascular and rheumatic diseases. The inhibition of the synthesis of inflammatory mediators by modulation of cyclooxygenase (COX) and lipoxygenase (LOX) pathways provides a challenging strategy for the development of more effective drugs. Objective: The aim of this study was to design dual COX-2 and 5-LOX inhibitors with iron-chelating properties using a combination of ligand-based (three-dimensional quantitative structure-activity relationship (3D-QSAR)) and structure-based (molecular docking) methods. Methods: The 3D-QSAR analysis was applied on a literature dataset consisting of 28 dual COX-2 and 5-LOX inhibitors in Pentacle software. The quality of developed COX-2 and 5-LOX 3D-QSAR models were evaluated by internal and external validation methods. The molecular docking analysis was performed in GOLD software, while selected ADMET properties were predicted in ADMET predictor software. Results: According to the molecular docking studies, the class of sulfohydroxamic acid analogues, previously designed by 3D-QSAR, was clustered as potential dual COX-2 and 5-LOX inhibitors with iron-chelating properties. Based on the 3D-QSAR and molecular docking, 1j, 1g, and 1l were selected as the most promising dual COX-2 and 5-LOX inhibitors. According to the in silico ADMET predictions, all compounds had an ADMET_Risk score less than 7 and a CYP_Risk score lower than 2.5. Designed compounds were not estimated as hERG inhibitors, and 1j had improved intrinsic solubility (8.704) in comparison to the dataset compounds (0.411-7.946). Conclusion: By combining 3D-QSAR and molecular docking, three compounds (1j, 1g, and 1l) are selected as the most promising designed dual COX-2 and 5-LOX inhibitors, for which good activity, as well as favourable ADMET properties and toxicity, are expected.

scholarly journals Quantitative Structure Activity Relationship (QSAR) Based on Electronic Descriptors and Docking Studies of Quinazoline Derivatives for Anticancer Activity

2018 ◽  
Vol 34 (5) ◽  
pp. 2361-2369
Author(s):  
Herlina Rasyid ◽  
Bambang Purwono ◽  
Ria Armunanto
Keyword(s):  
External Validation ◽  
Quantitative Structure Activity Relationship ◽  
Structure Activity Relationship ◽  
Docking Studies ◽  
Activity Relationship ◽  
Quantitative Structure ◽  
Qsar Analysis ◽  
Structure Activity ◽  
B3lyp Method ◽  
Quinazoline Derivatives

Quantitative structure-activity relationship (QSAR) based on electronic descriptors had been conducted on 2,3-dihydro-[1,4]dioxino[2,3-f]quinazoline analogues as anticancer using DFT/B3LYP method. The best QSAR equation described as follow: Log IC50 = -11.688 + (-35.522×qC6) + (-21.055×qC10) + (-85.682×qC12) + (-32.997×qO22) + (-85.129 EHOMO) + (19.724×ELUMO). Statistical value of R2 = 0.8732, rm2 = 0.7935, r2-r02/r2 = 0.0118, PRESS = 1.5727 and Fcalc/Ftable = 2.4067 used as external validation. Atomic net charge showed as the most important descriptor to predict activity and design new molecule. Following QSAR analysis, Lipinski rules was applied to filter the design compound due to physicochemical properties and resulted that all filtered compounds did not violate the rules. Docking analysis was conducted to determine interaction between proposed compounds and EGFR protein. Critical hydrogen bond was found in Met769 residue suggesting that proposed compounds could be used to inhibit EGFR protein.

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