Boronates react directly and stoichiometrically with peroxynitrite and hydrogen peroxide. For this reason, boronates have been widely used as peroxynitrite- and hydrogen peroxide-sensitive moieties in various donors of bioactive compounds. So far, numerous boronate-based prodrugs and theranostics have been developed, characterized, and used in biological research.
View Article and Find Full Text PDFMyeloperoxidase (MPO) is an important component of the human innate immune system and the main source of a strong oxidizing and chlorinating species, hypochlorous acid (HOCl). Inadvertent, misplaced, or excessive generation of HOCl by MPO is associated with multiple human inflammatory diseases. Therefore, there is a considerable interest in the development of MPO inhibitors.
View Article and Find Full Text PDFAzanone (HNO, also known as nitroxyl) is the protonated form of the product of one-electron reduction of nitric oxide (NO), and an elusive electrophilic reactive nitrogen species of increasing pharmacological significance. Over the past 20 years, the interest in the biological chemistry of HNO has increased significantly due to the numerous beneficial pharmacological effects of its donors. Increased availability of various HNO donors was accompanied by great progress in the understanding of HNO chemistry and chemical biology.
View Article and Find Full Text PDFMPO-derived oxidants including HOCl contribute to tissue damage and the initiation and propagation of inflammatory diseases. The search for small molecule inhibitors of myeloperoxidase, as molecular tools and potential drugs, requires the application of high throughput screening assays based on monitoring the activity of myeloperoxidase. In this study, we have compared three classes of fluorescent probes for monitoring myeloperoxidase-derived hypochlorous acid, including boronate-, aminophenyl- and thiol-based fluorogenic probes and we show that all three classes of probes are suitable for this purpose.
View Article and Find Full Text PDFAzanone (HNO) is an elusive electrophilic reactive nitrogen species of growing pharmacological and biological significance. Here, we present a comparative kinetic study of HNO reactivity toward selected cyclic -nucleophiles under aqueous conditions at pH 7.4.
View Article and Find Full Text PDFThe current pandemic outbreak clearly indicated the urgent need for tools allowing fast predictions of bioactivity of a large number of compounds, either available or at least synthesizable. In the computational chemistry toolbox, several such tools are available, with the main ones being docking and structure-activity relationship modeling either by classical linear QSAR or Machine Learning techniques. In this contribution, we focus on the comparison of the results obtained using different docking protocols on the example of the search for bioactivity of compounds containing N-N-C(S)-N scaffold at the S-protein of SARS-CoV-2 virus with ACE2 human receptor interface.
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