Monitoring the mechanism of anti-cancer agents to inhibit colorectal cancer cell proliferation: Enzymatic biosensing of glucose combined with molecular docking.

Glucose, a major energy source in cellular metabolism, has a significant role in cell growth. The increase in glucose uptake is a distinguishing hallmark in cancer cells. A key step in glucose utilization is the transport of glucose to the cancer cells for supplying their additional energy. The glucose transporter (or GLUT) family is a membrane protein which facilitates the uptake of glucose in most cancer cell types. Given the increased glucose level in cancer cells and the regulatory role of GLUTs in glucose uptake, it is required to combine both experimental and theoretical studies to develop new methods to monitor cell proliferation. Herein, for the first time, a new strategy was proposed to evaluate the cell proliferation of HT-29 based on glucose consumption in the presence of resveratrol (RSV) as an anticancer agent. A hybrid nanocomposite of carbon nanofibers and nitrogen-doped graphene quantum dots was used to design an enzymatic sensor for the selective and sensitive determination of glucose in cancer cells. The results obtained from the voltammetric technique were compared with the conventional colorimetric assay. A good correlation was observed between the proliferation rate and glucose utilization by cancer cells. As it was observed, RSV induces a decrease in glucose consumption, indicating lower glucose uptake efficiency for HT-29 cells. Molecular docking studies reveal that RSV can block the interaction of glucose with the GLUT family. This is one of the possible mechanisms for the decrease of glucose level followed by the reduction of cell proliferation in the presence of RSV. Compared with traditional methods, in vitro electrochemical techniques benefit from simple, nontoxic, sensitive and low-cost detection assays and hence serve as a novel tool to pursue the growth inhibition of cancer cell in response to anti-cancer agents.

Deciphering the inhibition effect of thymoquinone on xanthine oxidase activity using differential pulse voltammetry in combination with theoretical studies.

Xanthine oxidase (XO) catalyzes the oxidation of xanthine to uric acid. Over-production of uric acid is a risk factor for hyperuricemia and other diseases. Although allopurinol decreases uric acid levels, it causes severe adverse effects. Therefore, more effort is needed in finding novel XO inhibitors with fewer side effects. In this study, differential pulse voltammetry was used to investigate the inhibitory effect of thymoquinone (TQ) on the XO activity while the major problem was the overlap of the obtained signals. Thus, Parallel Factor Analysis (PARAFAC) was applied to extract the useful information. Also, docking was used to investigate how TQ and the active site of XO fit together. PARAFAC results based on the voltammetry studies revealed that TQ blocks the catalytic centers of XO, which leads to a decrease in the electrochemical signal of Mo center in XO. The results also indicated the dose-dependent inhibition of XO with TQ. Molecular docking studies were shown TQ surrounds the active sites of XO and reduces the oxidation of xanthine to uric acid. Therefore, the electrochemical response of Mo decreases in the presence of TQ. This finding is in good agreement with the results obtained from molecular docking studies.

Potentiality of PARAFAC approaches for simultaneous determination of N-acetylcysteine and acetaminophen based on the second-order data obtained from differential pulse voltammetry.

N-acetylcysteine (N-AC) has widespread application such as pharmaceutical drug and nutritional supplement. Its adverse effects are rash, urticaria, and itchiness and large doses of N-AC could potentially cause damage to the heart and lungs. Therefore, in this work, a sensitive voltammetric sensor based on a carbon paste electrode modified with silica nano particles (i.e. Mobil Composition of Matter (No. 41) modified with Boron Trifluoride or BF3@MCM-41) with a combination of 4,4'-dihydroxybiphenyl (DHB) (BF3@MCM-41/DHB/CPE) was designed for determination of N-AC. The electrochemical oxidation of N-AC was examined using various techniques such as cyclic voltammetry (CV), chronoamperometry and differential pulse voltammetry (DPV). Under the optimum conditions, some parameters such as electron transfer coefficient (α) and heterogeneous rate constant (ks) were estimated for N-AC. Due to the use of N-AC for the treatment of acetaminophen (AC) overdose, the application of modified electrode was investigated for the simultaneous determination of N-AC and AC in blood serum and tablet samples. Since, the signals of these species overlap and due to the presence of interfering species in blood samples, the simultaneous determination of mentioned species is difficult or impossible. To overcome this challenge, parallel factor analysis (PARAFAC) was used for the analysis of the complex matrices to obtain the spectral profile of each component and interference. To achieve this goal, electrochemical second-order data were generated using a simple change in pulse height of differential pulse voltammetry. The results of the presently proposed strategy for the real samples analysis are similar to those obtained with HPLC. Thus, the proposed method has acceptable performance for simultaneous determination of the two species in real samples.

An in-depth view of potential dual effect of thymol in inhibiting xanthine oxidase activity: Electrochemical measurements in combination with four way PARAFAC analysis and molecular docking insights.

Xanthine oxidase (XO) can catalyze xanthine to uric acid and has also been linked with the extension of some serious diseases such as cancer, gout, diabetes and so on. Thymol is a part of diet in the form of spices. Due to the high antioxidant activity, its inhibitory effect on XO was studied in the present work. XO organized in four redox domains which exhibiting electrochemical signals. Therefore, voltammetric methods can be used to obtain the valuable information about the action mechanism of thymol on XO. However, there are extreme complexities in these biological sample matrices which make the deeper understanding of inhibition mechanism of thymol on XO activity is difficult. Thus, development of electrochemical techniques coupled with the four-way parallel factor analysis (PARAFAC) has provided promising solutions for analyzing of complex matrix. To better explore this inhibitory effect, electrochemical technologies have been used as a complement with ultraviolet and visible (UV-Vis) spectroscopy and molecular docking studies. For the first time, molecular docking studies were used to gain a fundamental understanding to explain how the electron transfer coupling occurs at XO active sites in the presence of thymol. It is in good agreement with the experimental data. These studies reveal that thymol could enter into the catalytic centers of XO. Also, it inhibits the XO activity through the direct binding to flavin adenine dinucleotides (FAD) center. The results display dose-dependent inhibition of XO with thymol. Its inhibitory activity was linked to its antioxidant properties to reduce the formation of free radicals (FRs) and related diseases.

Chemometric studies of thymol binding with bovine serum albumin: A developing strategy for the successful investigation of pharmacological activity.

Thymol (Thy) is a hydrophobic active ingredient present in thyme essential oils. It is marginally soluble in water which is one of the challenging limitations for its application in foods or as drugs. An important aspect of our understanding from this system is to quantitatively comprehend how albumin interacts with Thy. Herein, this study has been focused on the interactions between thymol and bovine serum albumin (BSA) using electrochemical methods and ultraviolet and visible (UV-Vis) spectroscopy. Due to the overlap between obtained signals of existing species, it is apparent that multivariate methods can resolve overlapping signal trough unique decomposition. These obtained profiles are then analyzed to give the thermodynamic parameters, concentration and structural information of BSA binds to Thy. The thermodynamic results show that hydrogen bonding formation and van der Waals forces play major role in the binding process. Also, docking studies suggested that Thy binds mainly to the subdomain IIA of BSA through the formation of hydrogen bonding with Arg 217. Good agreement was found between the results obtained from experimental and theoretical studies. Thus, the current approaches seem to be promising that are not only for the transport of thymol in blood but also for its effective action in food applications.

New insights into the efficiency of thymol synergistic effect with p-cymene in inhibiting advanced glycation end products: A multi-way analysis based on spectroscopic and electrochemical methods in combination with molecular docking study.

Protein glycation in the body is one of the main reasons of diabetes complications. The electrochemical studies on the inhibitory mechanism of glycation are rather scarce. Thus, it is important to investigate the role of electrochemistry in the glycation process with basic chemometric frameworks. The aim of the current study is to investigate the anti-glycation effects of candidate compounds from thyme species i.e. thymol and p-cymene. To gain this objective, the electrochemical and absorption responses of glycated bovine serum albumin (BSA) in the absence and presence of inhibitors were recorded after 20 day of incubation. Due to the presence of multiple binding sites on BSA for the interaction with glucose, there are overlapping between the signals of these sites. Therefore, it is reasonable to use chemometric methods such as parallel factor analysis (PARAFAC) and alternating penalty trilinear decomposition (APTLD). The obtained results from chemometric methods showed that the solution of thymol at 5.0 mg mL-1 mixture with p-cymene (2.5 mg mL-1) was effective than thymol of 5.0 mg mL-1. Computational docking studies revealed the interaction pattern of thymol with BSA. The binding affinity of thymol was greater than glucose which it is in well agreement with the experimental data.

Monitoring the protective ability of thymoquinone mixture with p-cymene against bovine serum albumin (BSA) glycation: MCR-ALS analysis based on combined spectroscopic and electrochemical methods.

Protein glycation with sugars such as glucose start by the initial reaction between the carbonyl group of sugars and the amino group of proteins such as albumin and hemoglobin. This leads to the generation of Schiff base and following that the amadori and advanced glycation end products (AGEs). AGEs products can store in tissues and blood of diabetic patients. So, they play key roles to generate free radicals, which cause the development of diabetes complications. Inhibition of protein glycation plays an important role in controlling diabetes, so the identification of anti-glycation compounds is now receiving considerable interest. In this study, the protection effects of thymoquinone and its mixture with p-cymene on the glycation of bovine serum albumin (BSA) have been investigated by differential pulse voltammetry (DPV) and UV-vis spectrophotometry (UV-vis) techniques. Also, the multivariate curve resolution-alternating least squares (MCR-ALS) method was used since the results of the experimental measurements have a strongly overlapping signals. Molecular docking was applied to determine the site specific binding of inhibitor with residues of BSA. This study demonstrates that thymoquinone and its mixture with p-cymene have the potent ability to use as a dietary adjuvant against glycation.

Three-way spectrofluorimetric-assisted multivariate determination of nonylphenol ethoxylate and 2-naphtalene sulfonate in wastewater samples and optimization approach for their photocatalytic degradation by CoTiO3 nanostructure.

This study presents a new strategy for the simultaneous quantification of two industrial contaminants. The excitation-emission fluorescence data matrix combined with a three-way chemometric method, such as parallel factor analysis, was used for the determination of nonylphenol ethoxylate (NPE-9) as a nonionic surfactant and 2-naphthalene sulfonate (2-NS) in waste water samples. It is noticeable that this method can resolve overlapping signal into spectral and relative concentration profiles. By spiking the known concentrations of these compounds in the wastewater samples, the accuracy of the proposed methods was validated and recoveries of the spiked values were calculated. High recoveries (i.e. 90-110%) obtained for the waste water samples indicate the present method can be used successfully to determine the analytes concentration in the environmental contaminations. The photocatalytic degradation of NPE-9 and 2-NS in aqueous solution was studied using the CoTiO3 nanoparticles catalyst. It was synthesized by the sol-gel technique. The catalytic activity of the prepared nanoparticles was measured in a batch photoreactor containing appropriate solutions of these compounds with UV irradiation. The photodegradation process of these compounds was optimized by using the central composite design. The CoTiO3 showed high activity for UV-photocatalytic degradation of NPE-9 and 2-NS.

Spectrophotometric determination of synthetic colorants using PSO-GA-ANN.

Four common food colorants, containing tartrazine, sunset yellow, ponceau 4R and methyl orange, are simultaneously quantified without prior chemical separation. In this study, an effective artificial neural network (ANN) method is designed for modeling multicomponent absorbance data with the presence of shifts or changes of peak shapes in spectroscopic analysis. Gradient descent methods such as Levenberg-Marquardt function are usually used to determine the parameters of ANN. However, these methods may provide inappropriate parameters. In this paper, we propose combination of genetic algorithms (GA) and partial swarm optimization (PSO) to optimize parameters of ANN, and then the algorithm is used to process the relationship between the absorbance data and the concentration of analytes. The hybrid algorithm has the benefits of both PSO and GA techniques. The performance of this algorithm is compared to the performance of PSO-ANN, PC-ANN and ANN based Levenberg-Marquardt function. The obtained results revealed that the designed model can accurately determine colorant concentrations in real and synthetic samples. According to the observations, it is clear that the proposed hybrid method is a powerful tool to estimate the concentration of food colorants with a high degree of overlap using nonlinear artificial neural network.

Chemometrics-assisted excitation-emission fluorescence analytical data for rapid and selective determination of optical brighteners in the presence of uncalibrated interferences.

This study describes a novel approach for the simultaneous determination of CBS-X and CXT as widely used optical brighteners in household detergent, by combining the advantage of the high sensitivity of molecular fluorescence, and the selectivity of second-order chemometric methods. The proposed method is assisted by second-order chemometric analyses employing the PARAFAC, SWATLD and APTLD that help us to determine CBS-X and CXT in laundry powders and environmental samples, through the unique decomposition of the three-way data array. Proposed method can provide the extraction of relative concentrations of the analytes, as well as the spectral profiles. This approach achieves the second-order advantage and in principle could be able to overcome the spectral uncalibrated interference problems in the determination of CBS-X and CXT at the ng g(-1) level. By spiking the known concentrations of these compounds to the real samples, the accuracy of the proposed methods was validated and recoveries of the spiked values were calculated. High recoveries (90.00%-113.33%) for the spiked laundry powders and real environmental samples indicate the present method successfully faces this complex challenge without the necessity of applying separation and preconcentration steps in environmental contaminations.

Quality assessment of the saffron samples using second-order spectrophotometric data assisted by three-way chemometric methods via quantitative analysis of synthetic colorants in adulterated saffron.

Saffron is a valuable culinary spice that can be used not only for dyes and cooking, but also for many medical purposes. Due to its high price and restriction of its production, various fraud manners in its production have been growing. Addition of synthetic colorants to saffron is the most common way for adulteration. In this work, chemometric methods are proposed to resolve the three-dimensional absorbance spectra-pH data for simultaneous determination of the two colorants Tartrazin and Sunset yellow, in adulterated saffron. The rank deficiency in the concentration mode impaired the system. Therefore, to extirpate the ambiguity, which results from rank deficiency, three-way variation array V was generated by subtracting the first pH spectrum from each spectrum at each pH. This allows the extraction of extent reaction profile and mixture reaction spectral profiles, as well as the relative concentrations of the analytes.