Environmentally Friendly Quinolones Design for a Two-Way Choice between Biotoxicity and Genotoxicity through Double-Activity 3D-QSAR Model Coupled with the Variation Weighting Method

Quinolone (QN) antibiotics are widely used, which lead to their accumulation in soil and toxic effects on ryegrass in pasture. In this study, we employed ryegrass as the research object and selected the total scores of 29 QN molecules docked with two resistant enzyme structures, superoxide dismutase (SOD, PDB ID: 1B06) and proline (Pro, PPEP-2, PDB ID: 6FPC), as dependent variables. The structural parameters of QNs were used as independent variables to construct a QN double-activity 3D-QSAR model for determining the biotoxicity on ryegrass by employing the variation weighting method. This model was constructed to determine modification sites and groups for designing QNs molecules. According to the 3D contour map of the model, by considering enrofloxacin (ENR) and sparfloxacin (SPA) as examples, 23 QN derivatives with low biotoxicity were designed, respectively. The functional properties and environmental friendliness of the QN derivatives were predicted through a two-way selection between biotoxicity and genotoxicity before and after modification; four environmentally friendly derivatives with low biotoxicity and high genotoxicity were screened out. Mixed toxicity index and molecular dynamics methods were used to verify the combined toxicity mechanism of QNs on ryegrass before and after modification. By simulating the combined pollution of ENR and its derivatives in different soils (farmland, garden, and woodland), the types of combined toxicity were determined as partial additive and synergistic. Binding energies were calculated using molecular dynamics. The designed QN derivatives with low biotoxicity, high genotoxicity, and environmental friendliness can highly reduce the combined toxicity on ryegrass and can be used as theoretic reserves to replace QN antibiotics.

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Environment-friendly PCN derivatives design and environmental behavior simulation based on a multi-activity 3D-QSAR model and molecular dynamics

Journal of Hazardous Materials ◽

10.1016/j.jhazmat.2020.122339 ◽

2020 ◽

Vol 393 ◽

pp. 122339 ◽

Cited By ~ 3

Author(s):

Wenwen Gu ◽

Qing Li ◽

Yu Li

Keyword(s):

Molecular Dynamics ◽

Environmental Behavior ◽

3D Qsar ◽

Qsar Model ◽

Environment Friendly ◽

Behavior Simulation ◽

Simulation Based

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Potential Environmental Risk Characteristics of PCB Transformation Products in the Environmental Medium

Toxics ◽

10.3390/toxics9090213 ◽

2021 ◽

Vol 9 (9) ◽

pp. 213

Author(s):

Minghao Li ◽

Wei He ◽

Hao Yang ◽

Shimei Sun ◽

Yu Li

Keyword(s):

Environmental Risk ◽

Polychlorinated Biphenyl ◽

Degradation Products ◽

Organic Pollutant ◽

Environmentally Friendly ◽

3D Qsar ◽

Transformation Products ◽

Qsar Model ◽

Environmental Risks ◽

Environmental Media

The complementary construction of polychlorinated biphenyl (PCB) phytotoxicity and the biotoxicity 3D-QSAR model, combined with the constructed PCB environmental risk characterization model, was carried out to evaluate the persistent organic pollutant (POP) properties (toxicity (phytotoxicity and biotoxicity), bioconcentration, migration, and persistence) of PCBs and their corresponding transformation products (phytodegradation, microbial degradation, biometabolism, and photodegradation). The transformation path with a significant increase in environmental risks was analyzed. Some environmentally friendly PCB derivatives, exhibiting a good modification effect, and their parent molecules were selected as precursor molecules. Their transformation processes were simulated and evaluated for assessing the environmental risks. Some transformation products displayed increased environmental risks. The environmental risks of plant degradation products of the PCBs in the environmental media showed the maximum risk, indicating that the potential risks of the transformation products of the PCBs and their environmentally friendly derivatives could not be neglected. It is essential to further improve the ability of plants to degrade their transformation products. The improvement of some degradation products for environmentally friendly PCB derivatives indicates that the theoretical modification of a single environmental feature cannot completely control the potential environmental risks of molecules. In addition, this method can be used to analyze and evaluate environmentally friendly PCB derivatives to avoid and reduce the potential environmental and human health risks caused by environmentally friendly PCB derivatives.

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A 3D QSAR Model of 17β-HSD1 Inhibitors Based on a Thieno[2,3-d]pyrimidin-4(3H)-one Core Applying Molecular Dynamics Simulations and Ligand–Protein Docking

ChemMedChem ◽

10.1002/cmdc.200700271 ◽

2008 ◽

Vol 3 (3) ◽

pp. 461-472 ◽

Cited By ~ 26

Author(s):

Sampo Karkola ◽

Annamaria Lilienkampf ◽

Kristiina Wähälä

Keyword(s):

Molecular Dynamics ◽

Molecular Dynamics Simulations ◽

3D Qsar ◽

Qsar Model ◽

Protein Docking ◽

Dynamics Simulations

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Computational Investigation of Adenosine 5′- (α, β-methylene)- diphosphate (AMPCP) Derivatives as Ecto-5′-nucleotidase (CD73) Inhibitors by Using 3D-QSAR, Molecular Docking, and Molecular Dynamics Simulations

10.21203/rs.3.rs-873328/v1 ◽

2021 ◽

Author(s):

Jiatong Wen ◽

Heng Zhang ◽

Churen Meng ◽

Di Zhou ◽

Gang Chen ◽

...

Keyword(s):

Molecular Dynamics ◽

Molecular Docking ◽

Tumor Cells ◽

Binding Free Energy ◽

3D Qsar ◽

Qsar Model ◽

Field Analysis ◽

Dynamics Simulation ◽

Comfa Model ◽

Structure Activity

Abstract CD73, as a surface enzyme anchored on the outside of the cell membrane via glycosylphosphatidylinositol (GPI), can convert the AMP in the tumor cell microenvironment into adenosine to promote the growth of tumor cells. It has been overexpressed in many different types of human tumors, such as gastric cancer, pancreatic cancer, liver cancer and other tumor cells. Therefore, targeted inhibitors of CD73 are considered as potential tumor treatment methods. Due to the low bioavailability of nucleoside CD73 inhibitors, it is necessary to develop new inhibitors. In this study, through molecular docking, three-dimensional quantitative structure-activity relationship (3D-QSAR) and molecular dynamics (MD) simulations, a series of CD73 inhibitors were calculated and studied to reveal their structure-activity relationships. Through molecular docking studies, explore the possible mode of interaction between inhibitors and protein. Subsequently, a 3D-QSAR model was established by comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA). For the best CoMFA model, the Q2 and R2 values are 0.708 and 0.983, respectively, while for the best CoMSIA model, the Q2 and R2 values are 0.809 and 0.992, respectively. In addition, the stability of the complex formed by the two inhibitors and CD73 was evaluated by molecular dynamics simulation, and the results are consistent with the results of molecular docking and 3D-QSAR research. Finally, the binding free energy was calculated by the surface area method (MM-GBSA), and the results are consistent with the activities that Van Der Waals and Coulomb contribute the most during the binding process of the molecule to the CD73 protein. In conclusion, our research provides valuable information for the further development of CD73 inhibitors.

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Integration of Fuzzy Matter-Element Method and 3D-QSAR Model for Generation of Environmentally Friendly Quinolone Derivatives

International Journal of Environmental Research and Public Health ◽

10.3390/ijerph17093239 ◽

2020 ◽

Vol 17 (9) ◽

pp. 3239

Author(s):

Xixi Li ◽

Baiyu Zhang ◽

Wendy Huang ◽

Cuirin Cantwell ◽

Bing Chen

Keyword(s):

Density Functional ◽

Molecular Design ◽

Environmentally Friendly ◽

3D Qsar ◽

Qsar Model ◽

Spectral Intensity ◽

Field Analysis ◽

Genetic Toxicity ◽

Quinolone Derivatives ◽

Element Method

The environmental pollution of quinolone antibiotics (QAs) has caused rising public concern due to their widespread usage. In this study, Gaussian 09 software was used to obtain the infrared spectral intensity (IRI) and ultraviolet spectral intensity (UVI) of 24 QAs based on the Density Functional Theory (DFT). Rather than using two single-factor inputs, a fuzzy matter-element method was selected to calculate the combined effects of infrared and ultraviolet spectra (CI). The Comparative Molecular Field Analysis (CoMFA) was then used to construct a three-dimensional quantitative structure–activity relationship (3D-QSAR) with QAs’ molecular structure as the independent variable and CI as the dependent variable. Using marbofloxacin and levofloxacin as target molecules, the molecular design of 87 QA derivatives was carried out. The developed models were further used to determine the stability, functionality (genetic toxicity), and the environmental effects (bioaccumulation, biodegradability) of these designed QA derivatives. Results indicated that all QA derivatives are stable in the environment with their IRI, UVI, and CI enhanced. Meanwhile, the genetic toxicity of the 87 QA derivatives increased by varying degrees (0.24%–29.01%), among which the bioaccumulation and biodegradability of 43 QA derivatives were within the acceptable range. Through integration of fuzzy matter-element method and 3D-QSAR, this study advanced the QAs research with the enhanced CI and helped to generate the proposed environmentally friendly quinolone derivatives so as to aid the management of this class of antibiotics.

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Identification of potential quinoxalinone-based aldose reductase inhibitors by 3D-QSAR, molecular docking and molecular dynamics

RSC Advances ◽

10.1039/c6ra05649k ◽

2016 ◽

Vol 6 (57) ◽

pp. 51716-51724 ◽

Cited By ~ 2

Author(s):

Dan Zhou ◽

Jianbo Chen ◽

Yi Xu

Keyword(s):

Molecular Dynamics ◽

Molecular Docking ◽

Aldose Reductase ◽

Inhibitory Activity ◽

3D Qsar ◽

Qsar Model ◽

Structural Factors ◽

Factors Affecting ◽

Aldose Reductase Inhibitors ◽

Reductase Inhibitors

The 3D-QSAR model of aldose reductase (ARIs) inhibitors is built to gain insights into the key structural factors affecting the inhibitory activity. Based on the model, six new potential ARIs were designed.

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Theoretical Design and Process Control of Neonicotinoids Insecticides Suitable for Synergistic Degradation of Rhizobia and Carbon-fixing Bacteria in Soil

10.21203/rs.3.rs-612837/v1 ◽

2021 ◽

Author(s):

Zhengyang Deng ◽

Zhixing Ren ◽

Shuhai Sun ◽

Yujun Wang

Keyword(s):

Evaluation Method ◽

Comprehensive Evaluation ◽

Orthogonal Experiment ◽

Environmentally Friendly ◽

3D Qsar ◽

Qsar Model ◽

Binding Ability ◽

Comprehensive Evaluation Method ◽

Contour Maps ◽

Synergistic Degradation

Abstract This study studied and developed the modification schemes of environmentally friendly substitutes of NNIs along with the regulatory measures that effectively enhanced the synergistic degradation of NNIs by soil rhizobia and carbon-fixing bacteria. Firstly, the binding ability of NNIs to the two key proteins was characterized by molecular docking; Secondly, the mean square deviation decision method, which is a comprehensive evaluation method was used to investigate the binding ability of NNI molecules with the two Rubisco rate-limiting enzymes. The 3D-QSAR model was established for the synergistic degradation and single effect of rhizobia and carbon fixing bacteria, subsequently. Finally, after combining the 3D-QSAR model with a contour maps analysis of the synergistic degradation effect of soil rhizobia and carbon-fixing bacteria, 102 NNI derivatives were designed. 4 NNI derivatives passed the functional and environmentally friendly evaluation. Taguchi orthogonal experiment and factorial experiment assisted molecular dynamics method were used to simulate the effects of 32 regulation schemes on the synergistic degradation of NNIS and its derivatives by rhizobia and carbon fixing bacteria. The synergistic degradation capacity of soil rhizobia and carbon-fixing bacteria was increased to 33.32% after right nitrogen supplementation. This indicated that supplementing the correct amount of nitrogen was beneficial to the microbial degradation of NNIs and their derivatives.

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Computational Studies on Imidazo[1,2-a] Pyridine-3-Carboxamide Analogues as Antimycobacterial Agents: Common Pharmacophore Generation, Atom-based 3D-QSAR, Molecular dynamics Simulation, QikProp, Molecular Docking and Prime MMGBSA Approaches

Open Pharmaceutical Sciences Journal ◽

10.2174/1874844901805010012 ◽

2018 ◽

Vol 5 (1) ◽

pp. 12-23 ◽

Cited By ~ 10

Author(s):

Suraj N. Mali ◽

Hemchandra K. Chaudhari

Keyword(s):

Molecular Dynamics ◽

Molecular Docking ◽

Molecular Dynamics Simulation ◽

3D Qsar ◽

Qsar Model ◽

Dynamics Simulation ◽

Drug Resistant ◽

Drug Resistant Tuberculosis ◽

Resistant Tuberculosis ◽

Pharmacophore Hypothesis

Background: IMB-1402, Q203 and ND09759 analogs were found to have strong efficiency against Multi-drug-resistant tuberculosis (MDR-TB)/Extensively drug-resistant tuberculosis (XDR-TB) strains. Objectives: To know the structural necessities for imidazo[1,2-a]pyridine-3-carboxamide analogues, we intended to develop the ligand-based pharmacophore, Quantitative structure–activity relationship models(3D-QSAR model). We also performed Molecular docking, molecular simulation and Prime/Molecular Mechanics Generalized Born Surface Area (Prime/MM-GBSA) studies. Methods: All the studies like Common pharmacophore hypothesis generation, Atom based 3D-QSAR study, Prime MMGBSA, Docking, Qikprop, and Molecular dynamics simulation were processed using various modules incorporated within the maestro software interface from Schrodinger, LLC, New York USA (release 2017). Results: The common pharmacophore hypothesis(CPH) generation resulted in a five-featured hypothesis HHPRR, containing 1 positive, 2 hydrophobic and 2 aromatic rings. An Atom-based 3D-QSAR model was predicted for twenty seven training sets (a correlation coefficient i.e.R2= 0.9181,Standard deviation i.e.SD =0.3305, variance ratio i.e. F = 85.9) and eleven test sets (cross-validation correlation coefficient i.e.Q2 =0.6745, Root Mean Square Error i.e. RMSE = 0.65, Pearson R = 0.8427, P=1.21E-12) compounds employing alignment based on CPH. The dataset of thirty-eight molecules was allowed for docking into the active site of pantothenate synthetase (PDBID-3IVX) that shows H-bonding (Hydrogen bonding) interactions with residues Gly158, Met195, Pro38 and additionally shows further Pi-cation interactions with a residue like Hie47. We also obtained good simulation results for1.2ns study. Conclusion: From the results, the generated 3D-QSAR model may be applicable for additional designing of various novel potent derivatives in the future.

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