Electrochemical-based remote biomarker monitoring: Toward Internet of Wearable Things in telemedicine.

Internet of Wearable Things (IoWT) will be a major breakthrough for remote medical monitoring. In this scenario, wearable biomarker sensors have been developing not only to diagnose point-of-care (POC) of diseases, but also to continuously manage them. On-body tracking of biomarkers in biofluids is regarded as a proper substitution of conventional biomarker sensors for dynamic sampling and analyzing due to their high sensitivity, conformability, and affordability, creating ever-rising the market demand for them. In a wireless body area network (WBAN), data is captured from all sensors on the body to a smartphone/laptop, and sent the sensed data to a cloud for storing, processing, and retrieving, and ultimately displayed the data on custom applications (Apps). Wearable IoT biomarker sensors are used for early diseases diagnosis and continuous monitoring in developing countries in which people hardly access to healthcare systems. In this review, we aim to highlight a wide range of wearable electrochemical biomarker sensors, accompanied by microfluidics for continuous sampling, which will pave the way toward developing wearable IoT biomarker sensors to track health status. The current challenges and future perspective in skin-conformal biomarker sensors will be discussing their potential applicability for IoWT in cloud-based telemedicine.

In Silico Optimization of Frizzled-8 Receptor Inhibition Activity of Carbamazepine: Designing New Anti-Cancer Agent.

BACKGROUND: Frizzled-8 (FZD8) receptor is a therapeutic target for cancer treatment and recent research has shown that carbamazepine (CBZ) can inhibit this receptor. OBJECTIVE: In this work, it has been tried to optimize CBZ to enhance its binding capacity to the N6W binding site of FZD8 by using structure-based drug design methods. METHODS: CBZ and its 83 derivatives were docked to the N6W binding site of FZD8. RESULTS: Docking results show that two compounds 79 and 82 have the smallest binding energies and are fitted to the N6W binding site. Compounds C79 and C82 have been synthesized by replacing a hydrogen atom of the seven-membered ring in CBZ with benzoate and nicotinate groups, respectively. In addition, docking results show that a trifluoromethyl on one of the phenyl rings is favorable for improving the FZD8 inhibition activity of the molecule. CONCLUSION: Both molecules C79 and C82 were subjected to molecular dynamics (MD) simulation. MD results show that FZD8-C82 complex is stable and this compound binds to the N6W binding site more strongly than compounds C79 and CBZ.

QSAR analysis on a large and diverse set of potent phosphoinositide 3-kinase gamma (PI3Kγ) inhibitors using MLR and ANN methods.

Phosphorylation of PI3Kγ as a member of lipid kinases-enzymes, plays a crucial role in regulating immune cells through the generation of intracellular signals. Deregulation of this pathway is involved in several tumors. In this research, diverse sets of potent and selective isoform-specific PI3Kγ inhibitors whose drug-likeness was confirmed based on Lipinski's rule of five were used in the modeling process. Genetic algorithm (GA)-based multivariate analysis was employed on the half-maximal inhibitory concentration (IC50) of them. In this way, multiple linear regression (MLR) and artificial neural network (ANN) algorithm, were used to QSAR models construction on 245 compounds with a wide range of pIC50 (5.23-9.32). The stability and robustness of the models have been evaluated by external and internal validation methods (R2 0.623-0.642, RMSE 0.464-0.473, F 40.114, Q2LOO 0.600, and R2y-random 0.011). External verification using a wide variety of structures out of the training and test sets show that ANN is superior to MLR. The descriptors entered into the model are in good agreement with the X-ray structures of target-ligand complexes; so the model is interpretable. Finally, Williams plot-based analysis was applied to simultaneously compare the inhibitory activity and structural similarity of training, test and validation sets.

Fully united, easy, and economical sensor array for newborn babies' amino acids monitoring: Identification of amino acids in healthy and unhealthy with PKU newborn babies.

Amino acid (AA) disorders are the main class of inborn errors of metabolism with diverse medical presentations. This paper was aimed to provide a novel and efficient sensor array for the quantification and differentiation of AAs using different pH buffer solutions as sensor elements (SEs) and nanocurcumin (NC) in the role of a marker in biofluids of newborn babies. Amino and carboxyl groups along with the side chain of different AAs in different pH buffer solutions are protonated or deprotonated. This makes each AA molecule an acid (in the role of a proton donor), a hydrogen bonding donor, as well as a polar ion. So that, these differences may permit a profile differentiation-based sensor array for AAs discrimination. Using NC as a marker, the interactions between AA and NC in different pH buffer solutions (mainly involved in acid-base, hydrogen bonding, and π- π stacking interactions) result in absorbance changes, making a discriminate response profile for each AA. The results reveal that AAs can be discriminated successfully at three concentrations levels 10, 25, and 50 µM by linear discrimination analysis (LDA) and hierarchical clustering analysis (HCA). Complex AA mixtures are also capable to be classified. The results show that our sensor array can be potentially employed to the differentiation of AAs in biofluids of healthy and unhealthy newborn babies. It should be noted that the sensor array requires only common and available lab equipment and materials, which can be applied in AAs-related fundamental studies and clinical diagnosis.

Highly specific fingerprinting of alkaline earth metal ions by a tunable plasmonic nanosensor array based on nanoaggregation of metallochromic dyes-AuNPs.

Metal ions, specifically alkaline earth metal ions (AEMIs; Mg2+, Ca2+, Sr2+, and Ba2+), have essential roles in industrial processes, medical testing, and environmental evaluation; therefore, developing sensitive detection methods capable of their contents is highly required. To this aim, we have designed an absorbance nanosensor array using three metallochromic dyes decorated on AuNPs and have monitored variations in AuNP plasmonic profiles upon the addition of AEMIs in different buffer and pH solutions. The array is designed in a tunable size of 2 × 3 × 1(2/3); as the type buffer and pH of solution are fixed, the number of dyes can be changed in three individual modes, three binary modes, and a ternary mode, respectively. Owing to the different binding affinities of AEMIs toward dyes in different buffer and pH solutions, fingerprint-like plasmonic profiles with different levels of aggregation AuNPs were generated for all modes of array. These aggregation AuNP-based fingerprint profiles in the wavelengths of 500, 525, 550, 575, 600, 625, 650, 675, 700, 725, and 750 nm were used to discriminate the AEMIs by applying pattern recognition methods including linear discrimination analysis (LDA) and hierarchical clustering analysis (HCA) to identify each AEMI in the range 2.1-24.7 µM. Accordingly, limits of detection (LODs) values of 0.013 (±3.13), 0.014 (±2.99), 0.020 (±4.17), and 0.017 (±4.31) µM were obtained the Mg2+, Ca2+, Sr2+, and Ba2+, respectively. The results revealed that all the modes of array could well differentiate complex mixtures of the AEMIs. Our suggested array also exhibited a good performance in the differentiation of AEMIs in real samples and a certified reference material (CRM) sample.

A 3×3 visible-light cross-reactive sensor array based on the nanoaggregation of curcumin in different pH and buffers for the multivariate identification and quantification of metal ions.

Here, a facilely constructed 3 × 3 visible-light cross reactive sensor array based on nanoaggregation of curcumin (Cur) is proposed for the identification and quantification of metal ions (MIs). Synthesis of nanocurcumin (NCur) was characterized by UV-Vis spectrophotometry, transmission electron microscopy (TEM) and Fourier transform infrared (FT-IR). The average particle size was estimated about 5.21 ± 1.13 nm) n = 50 (. Our sensor array consists of nine receptors with distinct but overlapping specificities for 11 MIs: Al3+, Cd2+, Co2+, Cu2+, Hg2+, Fe2+, Fe3+, Mn2+, Ni2+, Pb2+, and Zn2+. The receptors include the nine solutions of NCur at three buffers of phosphate, ammonium, and tris each at three pH of 7, 8, and 9 (in total 9 receptors). On account of different pH and buffers, NCur-MI binding affinities can be distinguished by monitoring the UV-Vis absorbance changes. These changes are optical fingerprints that can be used to identify each MI. The absorption values in sixteen wavelengths (i.e. 332, 352, 372, 392, 412, 432, 452, 472, 492, 512, 532, 552, 572, 592, 612, and 632 nm) are considered as analytical signals to quantitatively evaluate of the absorbance responses of the sensor array. A color difference map is provided to qualitatively visualize of the colorimetric sensor array responses. Under optimal conditions, the MIs are successfully discriminated in the range of 4-48 µmol L-1. The limit of detections (LODs) values ranged from 0.47 (for Fe3+) to 1.40 µmol L-1 (for Pb2+). Furthermore, two different mixing sets of the MIs are prepared for multivariate multicomponent analysis. Finally, the suggested sensor array is employed to evaluate its practicability in the discrimination of MIs in samples of river water and serum. Moreover, it can identify the MIs in these samples. The sensor array presents a simple, save time, cost-effective, and environmentally friendly method for the identification and quantification of MIs.

Study of interaction of metal ions with methylthymol blue by chemometrics and quantum chemical calculations.

In this study, we determine the acidity constants of methylthymol blue (MTB) and association constants of its complexes with the ZnII, CuII, and FeII metal ions (MIs), through theoretical and experimental means. The complexes were characterized using UV-Visible absorption spectroscopy combined with soft/hard chemometrics methods and quantum chemical calculations. Quantum chemical calculations revealed that electronic transitions in the UV-Visible spectra of MTB have mixed n → π* and π → π* characters. The results of molar ratio and multivariate curve resolution alternating least squares (MCR-ALS) revealed the formation of successive 1:2 and 1:1 complexes (MI:MTB) for the ZnII and CuII systems. However, the formation of successive 1:1 and 2:1 complexes are suggested for FeII by the molar ratio and MCR-ALS. The majority of transitions observed in the UV-Visible spectra of the Zn(MTB) and Cu(MTB) complexes have ligand-to-ligand charge transfer (LLCT) characters. However, the transitions in the UV-Visible spectrum of the Fe(MTB) complex have LLCT and metal-to-ligand charge transfer (MLCT) characters. For the Fe2(MTB) complex, the lowest energy transition of has an LLCT character. However, its higher energy transitions are a mixture of LLCT, MLCT, and metal-to-metal charge transfer (MMCT) characters. The correlation between experimental and computed wavelengths revealed that the 1:1 complexes of ZnII and CuII prefer square pyramidal geometries. However, the FeII complexes always show octahedral geometry.

Phytochemicals toward Green (Bio)sensing.

Because of numerous inherent and unique characteristics of phytochemicals as bioactive compounds derived from plants, they have been widely used as one of the most interesting nature-based compounds in a myriad of fields. Moreover, a wide variety of phytochemicals offer a plethora of fascinating optical and electrochemical features that pave the way toward their development as optical and electrochemical (bio)sensors for clinical/health diagnostics, environmental monitoring, food quality control, and bioimaging. In the current review, we highlight how phytochemicals have been tailored and used for a wide variety of optical and electrochemical (bio)sensing and bioimaging applications, after classifying and introducing them according to their chemical structures. Finally, the current challenges and future directions/perspective on the optical and electrochemical (bio)sensing applications of phytochemicals are discussed with the goal of further expanding their potential applications in (bio)sensing technology. Regarding the advantageous features of phytochemicals as highly promising and potential biomaterials, we envisage that many of the existing chemical-based (bio)sensors will be replaced by phytochemical-based ones in the near future.

Facile Approach to Fabricate a Chemical Sensor Array Based on Nanocurcumin-Metal Ions Aggregates: Detection and Identification of DNA Nucleobases.

Here, a three-channel absorbance sensor array based on the nanocurcumin-metal ion (NCur-MI) aggregates is designed for the detection and identification of deoxyribonucleic acid nucleobases (DNA NBs) for the first time. For this purpose, the binding affinities of some of MIs (i.e., Co2+, Cr3+, Cu2+, Fe2+, Fe3+, Hg2+, Mn2+, Ni2+, V3+, and Zn2+) to the NCur to induce the aggregation were evaluated under various experimental conditions. Further studies reveal that in the presence of DNA NBs, the aggregates of NCur-Co2+, NCur-Ni2+, and NCur-Zn2+ show the diverse absorbance responses to the deaggregation of NCur depending on the binding affinity of each of DNA NBs to the metal ions Co2+, Ni2+, and Zn2+. These responses are distinguishable from one another. Thus, clear differentiation among the DNA NBs is achieved by linear discriminant analysis and hierarchical clustering analysis to generate clustering maps. The discriminatory capacity of the sensor array for the identification of the DNA NBs is tested in the ranges of 2.4-16 and 5.6-10.4 µM. Furthermore, a mixed set of the DNA NBs was prepared for multivariate multicomponent analysis. Finally, the practicability of the sensor array is confirmed by the discrimination of the DNA NBs in an animal DNA sample. It should be noted that the proposed array is the first example to fabricate an NCur-based sensor array for the simultaneous detection of DNA NBs.

Simultaneous optical detection of human serum albumin and transferrin in body fluids.

A nanocurcumin (NCur)-VO2+ ensemble-based optical nanoprobe is proposed for monitoring of human serum albumin (HSA) and transferrin (TF) in biofluids of serum and urine. The determination strategy of HSA and TF is based on the decrease of the absorbance/color intensity of NCur in the presence of VO2+ due to the formation of NCur-VO2+ ensemble. This leads to aggregation of the NCur and the color change of solution from orange to pale pink. Upon addition of HSA or TF, release of VO2+ from NCur-VO2+ ensemble occurs due to their stronger binding affinities to VO2+ in competition with the NCur. This leads to deaggregation of the NCur and recovery of the decreased absorption/color intensity within a defined time range. The absorption changes at λ = 455 and the color of NCur solution can be monitored spectrophotometrically or visually by a smartphone camera, respectively. Under optimal conditions, the analytical signals increase linearly in the ranges 50-200 nM (LOD = 11 nM) and 20-140 nM (LOD = 8 nM) for HSA and TF, respectively. The difference in the different affinities between the HSA and the TF for binding to VO2+ produces the unique time profiles of each protein. Therefore, the simultaneous determination of HSA and TF is provided by using the least-square support-vector machine (LS-SVM) model. The good recoveries and small errors of predicted values suggest that the nanoprobe is capable to resolve binary mixtures of HSA and TF. The method was applied to the simultaneous determination of HSA and TF in serum and urine samples. Graphical abstract.

A novel label-free colorimetric aptasensor for sensitive determination of PSA biomarker using gold nanoparticles and a cationic polymer in human serum.

In this colorimetric assay for sensitive detection of prostate specific antigen (PSA) tumor marker, adsorbed non-thiolated poly-Adenine aptamer (polyA Apt) on the gold nanoparticles (AuNPs) surface was used. By incubating the AuNPs and the PSA specific aptamer prior to target addition, polyA Apt adsorbed on the gold nanoparticles and could bind the target while preventing non-specific interactions. Adsorbed polyA Apt on the AuNPs prevents aggregation of them by poly(diallyldimethylammoniumchloride) (PDDA). Upon the addition of PSA, it bind to the polyA Apt and induce the formation of a secondary structure. Therefore, interaction between polyA Apt and PDDA is repressed and PDDA induce the aggregation of the AuNPs. This analytical platform produces a remarkable optical signal in the absence and presence of PSA that accompanied by a color change from red to blue. This effect as a sensing strategy can be observed with naked eyes and quantified by colorimetry via measurement of the ratio of absorbances at 680 nm and 520 nm. Fabricated aptasensor for detection of PSA is linear in the concentration range of 0.1-100 ng/ml with 20 pg/ml as the limit of detection (S/N = 3). Because of the selectively recognized for PSA in the presence of other interfering substances, this proposed assay applied to real samples for the rapid screening of PSA.

A nanocellulose-based colorimetric assay kit for smartphone sensing of iron and iron-chelating deferoxamine drug in biofluids.

The current work describes the development of a "nanopaper-based analytical device (NAD)", through the embedding of curcumin in transparent bacterial cellulose (BC) nanopaper, as a colorimetric assay kit for monitoring of iron and deferoxamine (DFO) as iron-chelating drug in biological fluids such as serum blood, urine and saliva. The iron sensing strategy using the developed assay kit is based on the decrease of the absorbance/color intensity of curcumin-embedded in BC nanopaper (CEBC) in the presence of Fe(III), due to the formation of Fe(III)-curcumin complex. On the other hand, releasing of Fe(III) from Fe(III)-CEBC upon addition of DFO as an iron-chelating drug, due to the high affinity of this drug to Fe(III) in competition with curcumin, which leads to recovery of the decreased absorption/color intensity of Fe(III)-CEBC, is utilized for selective colorimetric monitoring of this drug. The absorption/color changes of the fabricated assay kit as output signal can be monitored by smartphone camera or by using a spectrophotometer. The results of our developed sensor agreed well with the results from a clinical reference method for determination of Fe(III) concentration in human serum blood samples, which revealed the clinical applicability of our developed assay kit. Taken together, regarding the advantageous features of the developed sensor as an easy-to-use, non-toxic, disposable, cost-effective and portable assay kit, along with those of smartphone-based sensing, it is anticipated that this sensing bioplatform, which we name lab-on-nanopaper, will find utility for sensitive, selective and easy diagnosis of iron-related diseases (iron deficiency and iron overload) and therapeutic drug monitoring (TDM) of iron-chelating drugs in clinical analysis as well.

Spectrophotometric and visual determination of zoledronic acid by using a bacterial cell-derived nanopaper doped with curcumin.

A nanopaper-based analytical device (NAD) is described for a colorimetric metal-complexing indicator-displacement assay (M-IDA) for zoledronic acid (ZA). Bacterial cellulose nanopaper was doped with curcumin to obtain a chemosensor on which hydrophilic test zones were patterned via laser printing of hydrophobic walls. The color intensity of the test zones decreases in the presence of Fe(III) due to the formation of Fe(III)-curcumin complex. However, upon addition of ZA, Fe(III) ions preferably binds ZA. Subsequently, the color of the zone changes from light yellow to dark yellow. The changes in the absorption (measured at 427 nm) and of the color of the test stripe can be monitored visually, by using a digital camera, or by a spectrophotometer. Under optimal conditions, the analytical signals increase linearly in the 0.01-100 µM ZA concentration range, and the detection limits are 8.8 and 8.0 nM for smartphone and spectrophotometer-based methods, respectively. The method was employed to the determination of ZA in (spiked) urine, serum, saliva, and in pharmaceutical samples. Graphical abstract Schematic representation of a nanopaper-based analytical device based on curcumin-doped BC nanopaper (CDBC) integrated with smartphone for metal-complexing indicator-displacement assay of zoledronic acid (ZA). High affinity of ZA to Fe(III) on the NAD/CDBC leads to color change.

Development linear and non-linear QSAR models for predicting AXL kinase inhibitory activity of N-[4-(quinolin-4-yloxy)phenyl]benzenesulfonamides.

In this research, we used CoMFA, LSSVM and FFANN for creating QSAR models for predicting AXL Kinase inhibitory activity of N-[4-(Quinolin-4-yloxy)phenyl]benzenesulfonamides. A CoMFA model with three components was developed and CoMFA contour maps were interpreted to extract chemical features that influence the inhibitory activity of these molecules. R2 for train and test set of CoMFA model were 0.8900 and 0.8171, respectively. Model created by five Dragon descriptors and LSSVM model showed slightly better predictive power with respect to CoMFA model. R2 for train, test set of created LSSVM model were 0.0.8477 and 0.8218, respectively. Also, a FFANN model, using the same five descriptors, was developed with 2 neurons in its hidden layer and R2 for its train and test sets were 0.8314 and 0.8522, respectively. All created models were validated by calculating several statistical parameters and their applicability domain were investigated by calculating leverage. Furthermore, a homology model was built for Axl structure and molecules with the lowest and the greatest activity were docked to it and their interactions with Axl were investigated.

Two colorimetric ampicillin sensing schemes based on the interaction of aptamers with gold nanoparticles.

Two kinds of aptasensors for ampicillin (AMP) are described. The assay strategies include the use of gold nanoparticles (AuNPs) that were modified with (a) a thiolated aptamer (T-Apt), and (b) a non-thiolated polyadenine aptamer (polyA Apt). The AuNPs and the aptamers were brought to interaction prior to addition of AMP. T-Apt and polyA Apt are adsorbed on the AuNPs by different mechanisms. The adsorbed aptamer was able to bind the target while preventing non-specific interactions. Remarkably different optical absorbances (measured at 520 and 680 nm) are produced the absence and presence of AMP. The assay can selectively recognize AMP even in the presence of species of similar chemical structure. The T-Apt based assay has a linear response in the 1-600 nM AMP concentration range and a 0.1 nM limit of detection. The respective data for the polyA Apt assay are 1-400 nM and 0.49 nM. Graphical abstract Schematic presentation of the colorimetric aptasensor for ampicillin detection using two kinds of anti-ampicillin aptamers and gold nanoparticles. Polydiallyldimethylammonium chloride (PDDA) acts as aggregation agent.

A paper-based optical probe for chromium by using gold nanoparticles modified with 2,2'-thiodiacetic acid and smartphone camera readout.

A paper based analytical device is presented for the determination of Cr(III) and Cr(VI) using gold nanoparticles (AuNPs) modified with 2,2'-thiodiacetic acid. The modified AuNPs were characterized using UV-Vis spectrophotometry, Fourier transform infrared, dynamic light scattering, zeta potential, energy dispersive spectroscopy and transmission electron microscopy. Cr(III) ions induce the aggregation of the modified AuNPs, and the color of the nanoprobe changes from red to blue. This can be detected visually, or by colorimetry, or with a camera. No interference is observed in the presence of 19 other cations and anions. Cr(VI) (chromate) can be determined by after reduction to Cr(III) by using ascorbic acid and then quantified total Cr(III). The concentration of Cr(VI) is obtained by subtracting the concentration of Cr(III) from that of total chromium. Under optimal conditions, the ratio of the absorbances measured at 670 (blue) and 522 (red) increases linearly in the 1.0 nM to 22.1 µM chromium concentration range, with 0.66 nM (0.034 ppb) limit of detection (LOD) in solution. In case of the paper device, the linear range extends from 1.0 nM to 0.1 mM, and the LOD is 0.64 nM (0.033 ppb). The method was applied to the determination of chromium in spiked water, urine and dilutes human plasma, and results were confirmed by GF-AAS analysis. This method is highly selective, fast and portable, requires minimum volume of reagents and samples and no washing steps. Graphical abstract A paper based analytical device is presented for determination of Cr(III) and Cr(VI) using gold nanoparticles modified with 2,2'-thiodiacetic acid. In paper optical probe, linear range and limit of detection are 1.0 nM to 0.1 mM and 0.64 nM, respectively. The method was applied to the determination of total chromium in spiked water, urine and dilutes human plasma, and results were confirmed by GF-AAS analysis.

Towards the In-silico Design of New HSP90 Inhibitors: Molecular Docking and 3D-QSAR CoMFA Studies of Tetrahydropyrido [4, 3-d] Pyrimidine Derivatives as HSP90 Inhibitors.

BACKGROUND: HSP90 is necessary for the conformational maturation of proteins, proteins disaggregation, folding newly synthesized peptides and the refolding of denatured proteins. The inhibition of HSP90 leads to proteasomal degradations of client proteins that finally kill cancer cells. METHODS: In this research, molecular docking and comparative molecular field analysis (CoMFA) were used to investigate the interactions of tetrahydropyrido[4,3-d]pyrimidine derivatives with the N-terminal domain binding site of the HSP90 and predicting their inhibitory activities. RESULTS: A CoMFA model with five components and q2 of 0.81 was developed. R2 for training and test sets were 0.96 and 0.79, respectively. Based on extracted Contour maps for this CoMFA model, three new inhibitors with greater pIC50 with respect to the greatest active molecule in the data-set were designed by modifying molecule m45. Molecule m45 and designed inhibitors were docked to the N-terminal domain binding site of the HSP90. Designed inhibitors obtained lower binding energy with respect to m45. CONCLUSION: Based on extracted CoMFA contour maps, bulky substituents are favored for the R1 group and in R3 group, short and bulky substituents increase the activity of molecules. Less bulky and longer substituents are favored for R2. The molecular docking analysis of compound m45 with the N-terminal domain binding site of the HSP90 show hydroxyl group on phenyl ring is necessary to form hydrogen bonding with hydrophilic residues in binding site and a conserved water molecule. Molecule m45 has Pi-Sigma interaction with phenyl ring in the side chain of Phenylalanine 138 via isopropyl substituent on meta position of the phenyl ring. Also, Molecule m45 forms carbon-hydrogen bond with oxygen atoms at the side chain of Aspartic acid 54 and Asparagine 51 via its dimethylamine group. Others are Van der Waals interactions.

Predictive and Descriptive CoMFA Models: The Effect of Variable Selection.

Aims & Scope: In this research, 8 variable selection approaches were used to investigate the effect of variable selection on the predictive power and stability of CoMFA models. MATERIALS & METHODS: Three data sets including 36 EPAC antagonists, 79 CD38 inhibitors and 57 ATAD2 bromodomain inhibitors were modelled by CoMFA. First of all, for all three data sets, CoMFA models with all CoMFA descriptors were created then by applying each variable selection method a new CoMFA model was developed so for each data set, 9 CoMFA models were built. Obtained results show noisy and uninformative variables affect CoMFA results. Based on created models, applying 5 variable selection approaches including FFD, SRD-FFD, IVE-PLS, SRD-UVEPLS and SPA-jackknife increases the predictive power and stability of CoMFA models significantly. RESULT & CONCLUSION: Among them, SPA-jackknife removes most of the variables while FFD retains most of them. FFD and IVE-PLS are time consuming process while SRD-FFD and SRD-UVE-PLS run need to few seconds. Also applying FFD, SRD-FFD, IVE-PLS, SRD-UVE-PLS protect CoMFA countor maps information for both fields.

Enhanced Sensitivity to Detection Nanomolar Level of Cu2+ Compared to Spectrophotometry Method by Functionalized Gold Nanoparticles: Design of Sensor Assisted by Exploiting First-order Data with Chemometrics.

A simple, sensitive and efficient colorimetric assay platform for the determination of Cu2+ was proposed with the aim of developing sensitive detection based on the aggregation of AuNPs in presence of a histamine H2-receptor antagonist (famotidine, FAM) as recognition site. This study is the first to demonstrate that the molar extinction coefficients of the complexes formed by FAM and Cu2+ are very low (by analyzing the chemometrics methods on the first order data arising from different metal to ligand ratio method), leading to the undesirable sensitivity of FAM-based assays. To resolve the problem of low sensitivity, the colorimetry method based on the Cu2+-induced aggregation of AuNPs functionalized with FAM was introduced. This procedure is accompanied by a color change from bright red to blue which can be observed with the naked eyes. Detection sensitivity obtained by the developed method increased about 100 fold compared with the spectrophotometry method. This sensor exhibited a good linear relation between the absorbance ratios at 670 to 520nm (A670/520) and the concentration in the range 2-110nM with LOD=0.76nM. The satisfactory analytical performance of the proposed sensor facilitates the development of simple and affordable UV-Vis chemosensors for environmental applications.

Molecular docking and CoMFA studies of thiazoloquin(az)olin(on)es as CD38 inhibitors: determination of inhibitory mechanism, pharmacophore interactions, and design of new inhibitors.

In this research, molecular docking and 3D-QSAR studies were carried out on a series of 79 thiazoloquin(az)olin(on)es as CD38 inhibitors. Based on docking results, four interactions including hydrogen bonding with main chain of GLU-226 (H-M-GLU-226), Van der Waals interactions with side chain of TRP-125 (V-S-TRP-125), TRP-189 (V-S-TRP-189), and THR-221 (V-S-THR-221) were considered as pharmacological interactions. Active conformation of each ligand was extracted from docking studies and was used for carrying out 3D-QSAR modeling. Comparative molecular field analysis (CoMFA) was performed on CD38 inhibitory activities of these compounds on human and mouse. We developed CoMFA models with five components as optimum models for both data-sets. For human data-set, a model with high predictive power was developed. R2, RMSE, and F-test values for training set of this model were .94, .24, and 179.58, respectively, and R2 and RMSE for its test set were .92 and .32, respectively. The q2 and RMSE values for leave-one-out cross validation test on training set were .78 and .46, respectively, that demonstrate created model is robust. Based on extracted steric and electrostatic contour maps for this model, three inhibitors with pIC50 larger than 8.85 were designed.