Search academic texts

Information × Registration Number 0220U104297, 0120U100111 , R & D reports Title Search for new photocontrolled inhibitors of therapeutically important enzymes. popup.stage_title Head Kobzar Oleksandr L., к.х.н. Registration Date 16-12-2020 Organization V.P. Kukhar Institute of Bioorganic Chemistry and Petrochemistry of the National Academy of Sciences of Ukraine popup.description2 Alkyl- and aryl-α-ketophosphonates derivatives and α-ketophosphonate derivatives of calix[4]arene were for the first time studied as photocontrolled inhibitors of GST from equine liver and GST from human placenta, as well as human recombinant GSTA1-1 and GSTP1-1. Under experimental conditions, without irradiation of a model system containing an enzyme and a potential inhibitor, the alkyl- and aryl-α-ketophosphonates derivatives did not affect the activity of GSTase, and α-ketophosphonate derivatives of calix[4]arene were weak inhibitors of the enzymes. The inhibitory potential of the compounds was improved by photoactivation of model system by wavelength 365 nm. In this case, obtained IC50 values of alkyl- and aryl-α-ketophosphonate derivatives were in micromolar range, and IC50 value of α-ketophosphonate derivatives of calix[4]arene were decreased to micromolar and submicromolar range. According to the experimental results, the α-ketophosphonate derivatives are irreversible inhibitors of the enzymes. Kinetic parameters of the reactions, which include formation of an intermediate complex of α-ketophosphonate with enzyme and its further transformation, were analyzed based on kinetic studies. Molecular docking calculations revealed that compounds can be located between C- and N-terminal domains of GSTA1-1 leading to disruption of the enzyme catalytic activity. Moreover the compounds can occupy the region of active sites of GSTas near catalytically important amino acids residues Tyr7 and Tyr108 in structure of GSTP1-1, and Tyr9 in structure of GSTA1-1. Product Description popup.authors Buldenko Vladyslav M. Mrug Galyna P. Shulga Yrij V. popup.nrat_date 2020-12-15 Close