- Electrochemical degradation of sunscreen agent benzophenone-3 and its metabolite by Ti/SnO2-Sb/Ce-PbO2 anode: Kinetics, mechanism, toxicity and energy consumption. [Journal Article]
- STSci Total Environ 2019 Jun 14; 688:75-82
- Electrochemical degradation of sunscreen agent benzophenone-3 (BP-3) and its metabolite 4-hydroxybenzophenone (4-OH-BP) was investigated by using a Ti/SnO2-Sb/Ce-PbO2 anode. Results showed that the d…
Electrochemical degradation of sunscreen agent benzophenone-3 (BP-3) and its metabolite 4-hydroxybenzophenone (4-OH-BP) was investigated by using a Ti/SnO2-Sb/Ce-PbO2 anode. Results showed that the degradation of BP-3 and 4-OH-BP followed pseudo-first-order kinetics, and the rate constants were 0.083 and 0.113 min-1 at a current density of 25 mA cm-2, respectively. The electrochemical degradation of BP-3 and 4-OH-BP was efficient over a wide range of pH values, and the degradation was obviously accelerated in the presence of Cl-. Degradation intermediates were identified during the electrochemical process, and the degradation pathways, mainly including hydroxylation, carbonyl group broken from aromatic ring, benzene ring opening and carboxylation, were proposed. Quantitative structure-activity relationship model indicated that the potential risks of BP-3 and 4-OH-BP to fish, daphnia and green algae were decreased with the increase of reaction time. The energy consumption for the degradation of 90% BP-3 and 4-OH-BP was 3.3-62.1 and 3.6-79.5 Wh L-1, respectively. The results illustrate that the electrochemical technique with Ti/SnO2-Sb/Ce-PbO2 anode is expected to be an effective way for removing BP-3 and its metabolite 4-OH-BP from wastewater.
- Combinations of graph invariants and attributes of simplified molecular input-line entry system (SMILES) to build up models for sweetness. [Journal Article]
- FRFood Res Int 2019; 122:40-46
- The quantitative structure - activity relationships (QSARs) for sweetness value (log S) were built with a dataset of 315 molecules; following a novel criterion of 'Index of Ideality of Correlation(II…
The quantitative structure - activity relationships (QSARs) for sweetness value (log S) were built with a dataset of 315 molecules; following a novel criterion of 'Index of Ideality of Correlation(IIC)' This criterion of IIC is available in the latest version of the CORAL software (www.insilico.eu/coral). The descriptor used in the model building for log S is a hybrid optimal descriptor; obtained by combining the two descriptors: (i) molecular graph based descriptor derived from correlation weights of molecular features and (ii) descriptor derived from the simplified molecular input-line entry system (SMILES) code of sweetener molecule. The data set of 315 molecules was divided into four random splits. The four QSAR models which were build for log S using the criterion of IIC were compared with four similar models built "traditional protocol" described elsewhere. The comparison revealed that the models built using IIc were better with statistical performance.
- Molecular screening and docking analysis of LMTK3and AKT1 combined inhibitors. [Journal Article]
- BBioinformation 2018; 14(9):499-503
- The abnormal activation of AKT/mTOR signaling pathway and overexpression of LMTK3, are the main factors involved in the generation of drug resistance. Therefore, the use of computer-aided drug design…
The abnormal activation of AKT/mTOR signaling pathway and overexpression of LMTK3, are the main factors involved in the generation of drug resistance. Therefore, the use of computer-aided drug design in the inhibitors discovery offers an advantage to provide new candidates for the treatment of this resistance. We realised the virtual screening and molecular docking of AKT1 and LMTK3 proteins by the Dockblaster server. In addition, with abundance of candidates under development for AKT1 kinase, we have also conducted a Quantitative Structure-Activity Relationship (QSAR) study based on these compounds, in order to design more active compounds and predict their activity for development of a new inhibitor of AKT1. QSAR tests were performed for AKT1 using the Partial Least Squares method with a correlation coefficient of R2=0.8062 and a cross-validation of q2=0.6995. This test has selected five compounds as competitive inhibitors-AKT1-ATP with a better biological activities. In parallel the molecular screening has selected five other compounds as competitive ATP-inhibitors of LMTK3. One of them is a common inhibitor with AKT1, and it is marketed as a moderate to severe pain therapy. The ADME predictions confirmed the inhibitors pharmacological activity of these compounds for potential consideration as drug candidates.
- QSAR modeling, pharmacophore-based virtual screening, and ensemble docking insights into predicting potential epigallocatechin gallate (EGCG) analogs against epidermal growth factor receptor. [Journal Article]
- JRJ Recept Signal Transduct Res 2019 Jun 21; :1-10
- Epigallocatechin gallate (EGCG) is a major polyphenols of green tea may have the possibility to inhibit epidermal growth factor receptor (EGFR) activity and lead to reduce non-small cell lung cancer …
Epigallocatechin gallate (EGCG) is a major polyphenols of green tea may have the possibility to inhibit epidermal growth factor receptor (EGFR) activity and lead to reduce non-small cell lung cancer (NSCLC) progression. However, EGCG has some toxic features; moreover, there is a lack of explorations into the molecular interaction mechanisms of EGCG and the EGFR. In this examination, integration of quantitative structure-activity relationship (QSAR) modeling, pharmacophore-based virtual screening, and ensemble docking approaches were used to predict potential novel EGCG analogs as effective EGFR inhibitors. QSAR modeling of logP and logS predictions and toxicity endpoint investigation for a set of 82 compounds were shown good predictive ability and robustness from the applicability domain and confusion matrix elucidations. Virtual screening and docking studies revealed that seven high potential EGCG analogs as strong EGFR binders. Molecular interactions interpretations indicated some insights into the structural features of ligands that efficiently interfere with mutation possible residues (Gly719 and Thr790) of the EGFR. The hydrogen bonds, hydrophobic interactions, atomic π-cation interactions and salt bridges of ligands are contributing additional stability to receptor structure, which can lead to blocking the intracellular protein-tyrosine kinase activity, including EGFR associated pathways activation in NSCLC. Therefore, this can characterize as a block-cluster mechanism between EGCG analogs and EGFR complexes. In silico anti-EGFR and anticancer activity predictions suggested that, ligands could act as promising pharmacological, anticancer, and drug-like templates of EGFR towards moderating the NSCLC progressions. These results and provided pinpoints could be beneficial to recognize probable therapeutic targets for NSCLC therapy.
- Unlocking the potential of in silico chemical safety assessment - A report on a cross-sector symposium on current opportunities and future challenges. [Journal Article]
- CTComput Toxicol 2019; 10:38-43
- In silico chemical safety assessment can support the evaluation of hazard and risk following potential exposure to a substance. A symposium identified a number of opportunities and challenges to impl…
In silico chemical safety assessment can support the evaluation of hazard and risk following potential exposure to a substance. A symposium identified a number of opportunities and challenges to implement in silico methods, such as quantitative structure-activity relationships (QSARs) and read-across, to assess the potential harm of a substance in a variety of exposure scenarios, e.g. pharmaceuticals, personal care products, and industrial chemicals. To initiate the process of in silico safety assessment, clear and unambiguous problem formulation is required to provide the context for these methods. These approaches must be built on data of defined quality, while acknowledging the possibility of novel data resources tapping into on-going progress with data sharing. Models need to be developed that cover appropriate toxicity and kinetic endpoints, and that are documented appropriately with defined uncertainties. The application and implementation of in silico models in chemical safety requires a flexible technological framework that enables the integration of multiple strands of data and evidence. The findings of the symposium allowed for the identification of priorities to progress in silico chemical safety assessment towards the animal-free assessment of chemicals.
- Rational design of novel sirtuin 1 activators via structure-activity insights from application of QSAR modeling. [Journal Article]
- EJEXCLI J 2019; 18:207-222
- Sirtuin 1 (SIRT1) enzyme regulates major cell activities, and its activation offers lucrative therapeutic potentials for aging diseases including Alzheimer's disease (AD). Regarding the global aging …
Sirtuin 1 (SIRT1) enzyme regulates major cell activities, and its activation offers lucrative therapeutic potentials for aging diseases including Alzheimer's disease (AD). Regarding the global aging society, continual attention has been given to various chemical scaffolds as a source for the discovery of novel SIRT1 activators since the discovery of the pioneer activator, resveratrol. Understanding structure-activity relationship (SAR) is essential for screening, designing as well as improving the properties of drugs. In this study, an in silico approach based on quantitative structure-activity relationship (QSAR) modeling, was employed for understanding the SAR of currently available SIRT1 fused-aromatic activators (i.e., imidazothiazole, oxazolopyridine, and azabenzimidazole analogs). Three QSAR models constructed using multiple linear regression (MLR) provided good predictive performance (R 2 LOOCV = 0.729 - 0.863 and RMSE LOOCV = 0.165 - 0.325). An additional novel set of 181 structurally modified compounds were rationally designed according to key descriptors deduced from the QSAR findings and their SIRT1 activities were predicted using the constructed models. In overview, the study provides insightful SAR findings of currently available SIRT1 activators that would be useful for guiding the rational design, screening, and development of further potent SIRT1 activators for managing age-related clinical conditions. A series of promising compounds as well as important scaffolds and molecular properties for potent SIRT1 activator were highlighted. This study demonstrated the efficacious role of QSAR-driven structural modification for the rational design of novel leads.
- QSAR Models for Predicting Aquatic Toxicity of Esters Using Genetic Algorithm-Multiple Linear Regression Methods and Molecular Descriptors. [Journal Article]
- CCComb Chem High Throughput Screen 2019 Jun 18
- CONCLUSIONS: The predictive ability of the GA-MLR model with two selected molecular descriptors is satisfactory and it can be used for designing similar group and predicting of toxicity (log 1/IGC50) of ester derivatives.
- Application of a validated QSAR model for repurposing COX-2 inhibitor coumarin derivatives as potential antitumor agents. [Journal Article]
- CTCurr Top Med Chem 2019 Jun 18
- CONCLUSIONS: The promising results revealed that applied integrated in silico approach for repurposing by combining both the biological activity similarity and the molecular similarity via the computational method could be efficiently used to screen potential antitumor compounds among cyclooxygenase-2 inhibitors.
- Inhibition effect of natural flavonoids on red tide alga Phaeocystis globosa and its quantitative structure-activity relationship. [Journal Article]
- ESEnviron Sci Pollut Res Int 2019 Jun 17
- Red tides that occur off coasts have become a worldwide phenomenon over the past decades. In order to mitigate the damage of the red tides on the aquatic ecosystems, it is crucial to develop a method…
Red tides that occur off coasts have become a worldwide phenomenon over the past decades. In order to mitigate the damage of the red tides on the aquatic ecosystems, it is crucial to develop a method for predicting algicidal activities that requires less labor and time, and most importantly, this method can quickly screen potential algicides to control red tides. In this study, we have investigated the algicidal activity of 19 natural flavonoids against a typical red tide alga, Phaeocystis globosa. Our results indicate that after 5 days of flavonoid exposure, the half inhibition concentrations (IC50) ranged from 0.068 to 3.065 mg L-1, which showed the strong algicidal activities of the flavonoids. Furthermore, quantitative structure activity relationship (QSAR) model has been carried out between negative scale logarithm (pIC50) of the flavonoids and the corresponding molecular descriptors. The developed model was validated, both internally and externally, which displayed statistical robustness (R2 = 0.867, p = 0.0002, Q2LOO = 0.825, RMSEC = 0.182, Q2extF3 = 0.896, RMSEP = 0.161, CCC = 0.935). This indicates that the developed model was obtained successfully with satisfactory predictability and robustness for the future rapid screening of natural flavonoids with high inhibition activity on the red tide alga growth. Moreover, the main descriptors in the QSAR model were the molar refractivity, partition coefficient, lowest unoccupied molecular orbital, and highest occupied molecular orbital, illustrating that the molecular electro-chemical characteristics are significant in the algicidal actions of the flavonoids. Graphical abstract Red tides frequently occur worldwide and have become a global environment problem. Flavonoids showed great potential in allelopathic control of the excessive growth of red tide algae. In this study, the algicidal activity of 19 natural flavonoids was investigated on a typical red tide organism Phaeocystis globosa. Futhermore, we applied the quantitative structure-activity relationship (QSAR) model to the experimental data. The model between molecular descriptors of flavonoids and their antialgal activity displays statistical robustness, and 4 of 45 selected molecular descriptors were obtained by regression of training set. The numbers in the figure represent the half inhibition concentration (IC50) of flavonoids. Our results show that the algicidal activity of flavonoids is closely related to molar refraction, partition coefficient, lowest unoccupied molecular orbital, and highest occupied molecular orbital. The QSAR model can efficaciously predict the algicidal activity and provide insights into the inhibitory mechanisms of flavonoids.
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- Models for skin and brain penetration of major components from essential oils used in aromatherapy for dementia patients. [Journal Article]
- JBJ Biomol Struct Dyn 2019 Jun 23; :1-10
- Aromatherapy with essential oils (EOs) has been linked to improvement of cognitive function in patients with dementia. In order to act systemically, active EO components must be absorbed through the …
Aromatherapy with essential oils (EOs) has been linked to improvement of cognitive function in patients with dementia. In order to act systemically, active EO components must be absorbed through the skin, enter the systemic circulation, and cross the blood brain barrier (BBB). Thus, the aim of this work was to develop quantitative structure activity relationships (QSARs), to predict skin and blood barrier penetrative abilities of 119 terpenoids from EOs used in aromatherapy. The first model was based on experimentally measured skin permeability for 162 molecules, and the second model on BBB permeability for 138 molecules. Each molecule was encoded with 63 calculated molecular descriptors and an artificial neural network was used to correlate molecular descriptors to permeabilities. Developed QSAR models confirm that EOs components penetrate through the skin and across the BBB. Some well-known descriptors, such as log P (lipophilicity), molecular size and shape, dominated the QSAR model for BBB permeability. Compounds with the highest predicted BBB penetration were hydrocarbon terpenes with the smallest molecular size and highest lipophilicity. Thus, molecular size is a limiting factor for penetration. Compounds with the highest skin permeability have slightly higher molecular size, high lipophilicity and low polarity. Our work shows that a major disadvantage of novel multitarget compounds developed for the treatment of Alzheimer's disease is the size of molecules, which cause problems in their delivery to the brain. Therefore, there is a need for smaller compounds, which possess more desirable physicochemical properties and pharmacokinetics, in addition to targeted biological effects. Communicated by Ramaswamy H. Sarma.