Plant-based zinc nanoflowers assisted molecularly imprinted polymer for the design of an electrochemical sensor for selective determination of abrocitinib.

The first electrochemical sensor application in the literature is described for the sensitive and selective determination of the selective Janus kinase (JAK)-1 inhibitor abrocitinib (ABR). ABR is approved by the U.S. Food and Drug Administration (FDA) for the treatment of atopic dermatitis. The molecularly imprinted polymer (MIP)-based sensor was designed to incorporate zinc nanoflower (ZnNFs)-graphene oxide (GO) conjugate (ZnNFs@GO), synthesized from the root methanolic extract (RME) of the species Alkanna cappadocica Boiss. et Bal. to improve the porosity and effective surface area of the glassy carbon electrode (GCE). Furthermore, the MIP structure was prepared using ABR as a template molecule, 4-aminobenzoic acid (4-ABA) as a functional monomer, and other additional components. Scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared spectroscopy (FTIR) were used to characterize the surface and structure of the synthesized nanomaterial and MIP-based surface. Among the electrochemical methods, cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS) were preferred for detailed electrochemical characterization, and differential pulse voltammetry (DPV) was preferred for all other electrochemical measurements using 5.0 mM [Fe(CN)6]3-/4- solution as the redox probe. The MIP-based sensor, which was the result of a detailed optimization phase, gave a linear response in the 1.0 × 10-13 - 1.0 × 10-12 M range in standard solution and serum sample. The obtained limit of detection (LOD) and limit of quantification (LOQ) values and recovery studies demonstrated the sensitivity, accuracy, and applicability of the sensor. Selectivity, the most important feature of the MIP-based sensor, was verified by imprinting factor calculations using ibrutinib, ruxolitinib, tofacitinib, zonisamide, and acetazolamide.

A molecularly imprinted polymer-based electrochemical sensor for the determination of tofacitinib.

Tofacitinib citrate (TOF) is a Janus kinase-3 inhibitor used for rheumatoid arthritis treatment. In this study, a molecularly imprinted polymer (MIP)-based sensor was produced using acrylamide as the functional monomer via photopolymerization technique for the electrochemical determination of TOF. This study is the first one to explain the electrochemical determination of TOF with a highly selective MIP-based sensor. The surface characterization of the MIP-based sensor was performed with scanning electron microscopy and energy-dispersive X-ray spectroscopy methods, and it was expanded with electrochemical characterization by cyclic voltammetry and electrochemical impedance spectroscopy (EIS) methods. TOF determination was performed using differential pulse voltammetry (DPV) and EIS methods in standard solution and spiked serum sample in the linear range between 1×10-11 M and 1×10-10 M. Very low limit of detection and limit of quantification values were found, confirming the sensitivity of the sensor. Recovery analysis with spiked serum and tablet samples verified the sensor's accuracy and applicability using DPV and EIS methods. The selectivity of the sensor was confirmed with imprinting factor and interference studies, and the sensor performance was controlled using non-imprinted polymer for comparison at every step.

A semi-covalent molecularly imprinted electrochemical sensor for rapid and selective detection of tiotropium bromide.

Tiotropium bromide (TIO) is a long-acting bronchodilator used in the treatment of chronic obstructive pulmonary disease (COPD) and asthma. Specifically, it is used to prevent patients from worsening breathing difficulties. In this study, a new TIO-imprinted electrochemical sensor was designed to detect TIO in serum and pharmaceutical samples. Methacryloyl-L-histidine-cobalt(II) [MAH-Co(II)] has been used as a metal-chelating monomer for synthesizing selective molecularly imprinted polymer (MIP). MIP film has been developed on glassy carbon electrodes using MAH-Co(II) as the functional monomer, 2-hydroxyethyl methacrylate (HEMA) as the basic monomer, and ethylene glycol dimethacrylate (EGDMA) as the cross-linker in the photopolymerization method. The surface characterization of the developed MAH-Co(II)@MIP/GCE electrochemical sensor was done using scanning electron microscopy (SEM) and Fourier transform infrared spectroscopy (FTIR). Also, the electrochemical behavior of the sensor was provided by differential pulse voltammetry (DPV), cyclic voltammetry (CV), and electrochemical impedance spectroscopy (EIS) techniques. Under optimized experimental conditions, the linearity range was in the range of 10-100 fM, and the limit of detection (LOD) and limit of quantitation (LOQ) values were calculated as 2.73 fM and 9.75 fM, respectively. The MAH-Co(II)@MIP/GCE sensor was used to precisely determine TIO in capsule and commercial serum samples. The results demonstrated that the MIP could specifically recognize TIO compared to structurally related drugs and could be reliably applied to the direct determination of drugs from real samples.

Novel inhibitors of eukaryotic elongation factor 2 kinase: In silico, synthesis and in vitro studies.

Eukaryotic elongation factor 2 kinase (eEF2K) is an unusual alpha kinase whose expression is highly upregulated in various cancers and contributes to tumor growth, metastasis, and progression. More importantly, eEF2K expression is associated with poor clinical outcome and shorter patient survival in breast, lung and ovarian cancers. Therefore, eEF2K is an emerging molecular target for development of novel targeted therapeutics and precision medicine in solid cancers. Currently, there are not any available potent and specific eEF2K inhibitors for clinical translation. In this study, we designed and synthesized a series of novel compounds with coumarin scaffold with various substitutions and investigated their effects in inhibiting eEF2K activity using in silico approaches and in vitro studies in breast cancer cells. We utilized an amide substitution at position 3 on the coumarin ring with their pharmacologically active groups containing pyrrolidine, piperidine, morpholine and piperazine groups with (CH2)2 bridged for aliphatic amides. Due to their ability to form covalent binding to the target enzyme, we also investigated the effects of boron containing groups on functionalized coumarin ring (3 compounds) and designed novel aliphatic and aromatic derivatives of coumarin scaffolds (10 compounds) and phenyl ring with boron groups (4 compounds). The Glide/SP module of the Maestro molecular modeling package was used to perform in silico analysis and molecular docking studies. According to our combined results, structure activity relationship (SAR) was performed in detail. Among the newly designed, synthesized, and tested compounds, our in vitro findings revealed that several compounds displayed a highly effective eEF2K inhibition at submicromolar concentrations in in vitro breast cancer cells. In conclusion, we identified novel compounds that can be used as eEF2K inhibitors and that they should be further evaluated by in vivo preclinical tumor models studies for antitumor efficacy and clinical translation.

A molecularly imprinted polymer-based detection platform confirmed through molecular modeling for the highly sensitive and selective analysis of ipratropium bromide.

This study presented a new method to design a MIP-based electrochemical sensor that could improve the selective and sensitive detection of ipratropium bromide (IPR). The polymeric film was designed using 2-hydroxyethyl methacrylate (HEMA) as the basic monomer, 2-hydroxy-2-methylpropiophenone as the initiator, ethylene glycol dimethacrylate (EGDMA) as the crosslinking agent, and N-methacryloyl-L-aspartic acid (MAAsp) as the functional monomer. The presence of MAAsp results in the functional groups in imprinting binding sites, while the presence of poly(vinyl alcohol) (PVA) allows the generation of porous materials not only for sensitive sensing but also for avoiding electron transport limitations. Electrochemical characterizations of the changes at each stage of the MIP preparation process were confirmed using cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). In addition, morphological characterizations of the developed sensor were performed using scanning electron microscopy (SEM), attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR), and contact angle measurements. Theoretical calculations were also performed to explain/confirm the experimental results better. It was found that the results of the calculations using the DFT approach agreed with the experimental data. The MAAsp-IPR@MIP/GCE sensor was developed using the photopolymerization method, and the sensor surface was obtained by exposure to UV lamp radiation at 365 nm. The improved MIP-based electrochemical sensor demonstrated the ability to measure IPR for standard solutions in the linear operating range of 1.0 × 10-12-1.0 × 10-11 M under optimized conditions. For standard solutions, the limit of detection (LOD) and limit of quantification (LOQ) were obtained as 2.78 × 10-13 and 9.27 × 10-13 M, respectively. The IPR recovery values for the inhalation form were calculated as 101.70 % and 100.34 %, and the mean relative standard deviations (RSD) were less than 0.76 % in both cases. In addition, the proposed modified sensor demonstrated remarkable sensitivity and selectivity for rapid assessment of IPR in inhalation forms. The sensor's unique selectivity is demonstrated by its successful performance even in the presence of IPR impurities.

An electrochemical sensor based on carbon nanofiber and molecular imprinting strategy for dasatinib recognition.

Herein, we proposed a new approach to design a MIP-based electrochemical sensor with carbon nanofiber (CNF), which could improve its conductivities as well as electrode sensitivity and successful detection of dasatinib (DAS). CNFs are capable of forming high porosity with significant interconnected porous networks. The poly(2-hydroxyethyl-methacrylate-N-methacryloyl-L-tyrosine) (PHEMA-MATyr) copolymer was synthesized in the presence of both CNF and DAS by photopolymerization. After optimization of the parameters, the modified MIP-based electrochemical sensor demonstrated the ability to determine the DAS in the linear working range of 1.0 × 10-14-1.0 × 10-13 M for the standard solution and commercial serum samples with a LOD of 1.76 × 10-15 and 2.46 × 10-15, respectively. Good linearity for DAS was observed with correlation coefficients (r) of 0.996 and 0.997 for the standard solution and commercial serum samples, respectively. The recoveries of the DAS ranged from 99.45 % to 99.53 % for the tablet dosage form and commercial serum samples, with average relative standard deviations below 1.96 % in both cases. The proposed modified sensor demonstrated significant sensitivity and selectivity for the rapid determination of DAS in commercial serum samples and tablet form.

The electrochemical quantitation method for sugammadex via a molecularly imprinted polymer-based sensor.

Sugammadex (SUG) is a synthetically modified γ-cyclodextrin derivative used in hospitals after surgeries to reverse the neuromuscular blockade induced by rocuronium or vecuronium. In this study, we aimed to develop the first electroanalytical quantification method for sugammadex by using molecular imprinting (MIP) via the electropolymerization (EP) technique. An EP-MIP film was formed by EP on a screen-printed gold electrode (SPAuE) and a new electrochemical sensor, EP-MIP(SUG)/SPAuE, was fabricated using the 4-aminophenol monomer with copper ions to enhance the MIP-binding site. Surface and electrochemical characterization of the EP-MIP(SUG)/SPAuE sensor have been done via scanning electron microscopy (SEM), energy dispersive X-ray spectroscopy (EDX), cyclic voltammetry (CV) and electrochemical impedance spectroscopy (EIS). After screening and optimization studies were carried out to fabricate a MIP-based electrochemical sensor, the analytical performance of EP-MIP(SUG)/SPAuE and the validation parameters were tested according to the ICH guidelines. The specificity/selectivity of the developed sensor has been shown by using common interferents found in the biological fluids and also molecules having similar structures, such as α-cyclodextrin, ß-cyclodextrin, and γ-cyclodextrin. As a result, a quantitative analysis method has been developed and validated by using the EP-MIP(SUG)/SPAuE sensor in the concentration range of 0.1-1.0 pM with very high sensitivity (limit of detection: 27.3 fM). The applicability of the method has been shown for bulk drug substances, pharmaceutical dosage forms, and commercial serum samples with good recovery and RSD% results. The EP-MIP(SUG)/SPAuE is the first electrochemical sensor developed for the determination of sugammadex serving the aims of simplicity, short analysis time, and low cost, and has the potential to be adapted in the future as a portable and/or wearable sensor via miniaturization.

Development of highly selective and sensitive molecularly imprinted polymer-based electrochemical sensors for tolvaptan assay in tablets and serum.

In this research, two different molecularly imprinted polymer (MIP)-based electrochemical sensors were proposed for the determination of tolvaptan (TOL). Photopolymerization (PP) and thermal polymerization (TP) techniques were developed for the determination of TOL. The advantages of MIP were used to design an electrochemical sensor for selective and sensitive determination of TOL. TOL was determined on a glassy carbon electrode (GCE) using differential pulse voltammetry (DPV) for both techniques. Some important parameters affecting the sensor efficiency, such as template/monomer ratio, PP and TP time, drop volume, removal solutions, removal and rebinding time, etc., were optimized. The surface characterization of the proposed MIP-based electrochemical sensors was carried out with electrochemical characterization by electrochemical impedance spectroscopy (EIS) and cyclic voltammetry (CV) methods. It was extended with the scanning electron microscopy (SEM) technique. Under optimal conditions, the developed sensors showed good linearity between 1.0 × 10-11 M and 1.0 × 10-10 M, and 2.5 × 10-11 M and 2.5 × 10-10 M for PP and TP, respectively. Low detection limits (2.89 × 10-12 M (PP) and 1.88 × 10-13 M (TP)) were also obtained for TOL determination. The applicability of the proposed sensor was evaluated using tablet and commercial human serum samples. Interference and imprinting factor studies verified the selectivity and specificity of the proposed sensors, and the efficiency of the sensors was verified using an unprinted polymer for comparison at each step.

Human hair rich in pyridinic nitrogen-base DNA biosensor for direct electrochemical monitoring of palbociclib-DNA interaction.

Carbon material derived from the waste-based biomass human hair (H), which is naturally rich in pyridinic nitrogen, provides a significant benefit in biosensor applications with its dominant conductivity character. The carbon material was synthesized from human hair waste by the hydrothermal carbonization (HTC) method, which is a promising green synthesis. A morphological characterization of the carbon materials was performed. In this study, H and amine-functionalized multi-walled carbon nanotubes (NH2-MWCNT) were combined for the first time as a modifier, which enhanced the glassy carbon electrode (GCE) surface area for deoxyribonucleic acid (DNA) biosensor studies. Palbociclib (PLB) is clinically used in the treatment of breast cancer. The novel electrochemical nanobiosensor was used to investigate the dsDNA-PLB interaction to evaluate the possibility that PLB causes conformational changes in DNA structure and/or oxidative damage. The interaction was conducted based on the voltammetric signals of deoxyguanosine (dGuo) and deoxyadenosine (dAdo) by differential pulse voltammetry (DPV) on a bare and H + NH2-MWCNT modified GCE. The proposed analytical method was applied to a pharmaceutical dosage form with a satisfactory recovery of 98.25 %. The nanobiosensor was tested in the presence of some interfering agents. The binding mechanism of dsDNA-PLB was also evaluated by spectroscopic and theoretical calculations.

A molecularly imprinted electrochemical sensor based on highly selective and an ultra-trace assay of anti-cancer drug axitinib in its dosage form and biological samples.

In this study, a novel, fast, selective, and sensitive molecularly imprinted polymer (MIP)-based electrochemical sensor was developed to determine axitinib (AXI) at low concentrations in pharmaceutical dosage forms and human serum. The newly developed MIP-based sensor (MIP@o-PD/GCE) was designed through electropolymerization of functional monomer o-phenylenediamine (o-PD) in the presence of a template molecule AXI, on a glassy carbon electrode (GCE) using cyclic voltammetry. Differential pulse voltammetry and electrochemical impedance spectroscopy (EIS) techniques were employed for removal and rebinding processes, optimization of conditions, as well as for performance evaluation of MIP@o-PD/GCE using [Fe(CN)6]3-/4- as the redox probe. Under the optimum experimental conditions, MIP@o-PD/GCE shows a linear response toward AXI in a range of 1 × 10-13 M - 1 × 10-12 M. The limit of the detection value of MIP@o-PD/GCE was found as 0.027 pM while the limit of the quantification was obtained as 0.089 pM, respectively. To demonstrate the applicability and validity of the developed sensor, it was successfully applied to tablet dosage form and human serum sample. The selectivity of the sensor was qualified by comparing the binding of AXI, erlotinib, dasatinib, nilotinib, and imatinib, which are similarly structured and in the same group of anticancer drugs. MIP@o-PD/GCE sensor showed a significant selectivity toward AXI. The non-imprinted polymer (NIP) based GCE was prepared and used to control the analytical performance of the MIP-based electrochemical sensor.