Abstract

In this paper, we propose the first analytical procedure—using a screen-printed carbon electrode modified with carbon nanofibers (SPCE/CNFs)—for the detection and quantitative determination of an electroactive disubstituted fused triazinone, namely 4-Cl-PIMT, which is a promising anticancer drug candidate. The electrochemical performances of the sensor were investigated by cyclic voltammetry (CV), electrochemical impedance spectroscopy (EIS), and square-wave adsorptive stripping voltammetry (SWAdSV). The presence of carbon nanofibers on the sensor surface caused a decrease in charge-transfer resistance and an increase in the active surface compared to the bare SPCE. Under the optimised experimental conditions, the proposed voltammetric procedure possesses a good linear response for the determination of 4-Cl-PIMT in the two linear ranges of 0.5–10 nM and 10–100 nM. The low limits of detection and quantification were calculated at 0.099 and 0.33 nM, respectively. In addition, the sensor displays high reproducibility and repeatability, as well as good selectivity. The selectivity was improved through the use of a flow system and a short accumulation time. The SWAdSV procedure with SPCE/CNFs was applied to determine 4-Cl-PIMT in human serum samples. The SWAdSV results were compared to those obtained by the ultra-high-performance liquid chromatography coupled with electrospray ionization/single-quadrupole mass spectrometry (UHPLC-ESI-MS) method.

Highlights

  • Among pharmaceutically important disubstituted fused triazinones, 4-Cl-PIMT (i.e., 8-(4-chlorophenyl)-3-phenyl-7,8-dihydroimidazo[2,1-c][1,2,4]triazin-4(6H)-one; Figure 1), with a fully defined molecular structure, is the most promising anticancer drug candidate

  • In the initial stage of the experiments, we compared the voltammetric response of the title compound at the commercially available unmodified screen-printed carbon electrode (SPCE), screen-printed carbon electrode modified with carbon nanofibers (SPCE/CNFs), and screenprinted carbon electrode modified with multiwalled carbon nanotubes (SPCE/MWCNTs)

  • The analytical signals obtained at the SPCE/CNFs were significantly improved compared to those obtained at the SPCE and the SPCE/MWCNTs

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Summary

Introduction

Among pharmaceutically important disubstituted fused triazinones, 4-Cl-PIMT (i.e., 8-(4-chlorophenyl)-3-phenyl-7,8-dihydroimidazo[2,1-c][1,2,4]triazin-4(6H)-one; Figure 1), with a fully defined molecular structure, is the most promising anticancer drug candidate. This innovative nucleobase-like molecule revealed significant, concentrationdependent antiproliferative effects in human peripheral blood myeloma cells, indicating a possible usefulness in the treatment of such haematological malignancies. This compound proved to have the strongest antimigratory property in human tumour cells of the cervix among all disubstituted fused triazinones, suggesting the highest antimetastatic potential and, an applicability in the prevention of metastasis [1]. Sci. 2022, 23, x FOR PEER REVIEW agent, was found to be completely nontoxic to normal human skin fibroblast [1] and completely nontoxic to normal human [1] and green

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