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Information × Registration Number 0224U033423, (0124U001926) , R & D reports Title Creation of modern calixarene regulators of biochemical processes for medicine and biotechnology. Chapter 3. Search, design and establishment of properties of new potentially bioactive calixarene derivatives aimed at therapeutically important protein targets. popup.stage_title Пошук, конструювання і встановлення властивостей нових потенційно біоактивних похідних калікс[4]арену, спрямованих на терапевтично важливі протеїнові мішені. Механізми інгібування протеїнтирозинфосфатаз, глутатіон-S-трансфераз та інших ензимів Head Vovk Andrii I., Доктор хімічних наук Registration Date 27-12-2024 Organization V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine popup.description1 The purpose of the work is to search, design and establish the properties of new potentially bioactive organic and elementoorganic derivatives of calix[4]arene, aimed at known proteins as targets for the treatment of type 2 diabetes, as well as for antitumor therapy. The project involves the in vitro and in silico study of new inhibitors of protein tyrosine phosphatases and some other enzymes that catalyze the hydrolysis of phosphate bonds, as well as inhibitors of glutathione-S-transferases. popup.description2 The activity of calix[4]arene derivatives as inhibitors of protein tyrosine phosphatases and glutathione-S-transferases was assessed by molecular docking, taking into account the conformational state of the ligand, the nature of the scaffold, and the substituents on the upper and lower rings of the macrocycle. The ligand-binding sites of protein tyrosine phosphatase 1B were clustered. In vitro experiments revealed the features of the inhibitory effects of calix[4]arene methylenebisphosphonic acids on the activity of protein tyrosine phosphatases PTP1B, TC-PTP, MEG1, MEG2, SHP-2, VE-PTP, and PRL3. Amphiphilic anionic calix[4]arene derivatives were evaluated as potential inhibitors of glutathione-S-transferase and nucleotide pyrophosphatase/phosphodiesterase 1. The features of glutathione-S-transferase inhibition by calix[4]arenephosphoric acids were studied. The effect of calix[4]arene phosphonic acids on α-glucosidase activity was established for the first time. Sulfamide derivatives of calix[4]arene phosphonic acids were identified as new inhibitors of protein tyrosine phosphatases and α-glucosidase. It was established that the inhibitory effects of phosphonic acids with a calixarene scaffold on α-glucosidase activity depend on the nature of the macrocycle, increasing when going from calix[4]arene derivatives to thiacalix[4]arene and calix[6]arene derivatives. Based on kinetic data and computer modeling results, the mechanisms of action and the structure-activity relationship of calixarenes derivatives were substantiated. The obtained results may be used in further studies of macrocyclic phosphonic acid derivatives as potential inhibitors of therapeutically important enzymes. Product Description popup.authors Buldenko Vladyslav M. Kobzar Oleksandr L. Shulha Yrij V. popup.nrat_date 2024-12-27 Close