Buldenko V. Sulfonylcalix[4]arene as a new platform for the design of phosphatase inhibitors.

Іnhibition patterns of some therapeutically important phosphatases by macrocyclic compounds with a sulfonylcalix[4]arene scaffold. The effect of sulfonylcalix[4]arene, unsubstituted on the upper rim, on activity of protein tyrosine phosphatase in vitro was shown. It was found that sulfonylcalix[4]arene is a potential inhibitor of MEG2 with selectivity in comparison to PTP1B and TC-PTP, displaying low activity towards SHP2, PTPβ, and MEG1. The influence of some nonionogenic derivatives of sulfonylcalix[4]arene on activity of a number of human protein tyrosine phosphatases PTP1B, TC-PTP, SHP2, MEG2, MEG1, and РТРβ was shown and compared with activity of sulfonylcalix[4]arene phosphonic acids. As a result of the study of phosphinic acid derivatives on the macrocyclic platform, effective and selective inhibitors of PTP1B were found among derivatives of sulfonylcalix[4]arene and its structural analogues – calix[4]arene and thiacalix[4]arene. The ability of phosphonate derivatives of sulfonylcalix[4]arene to effectively inhibit nucleotidepyrophosphatase/phos-phodiesterase 1, displaying selectivity compared to its closely related alkaline phosphatases was shown. By means of fluorescence spectroscopy and computer modeling method, it was demonstrated the ability of sulfonylcalix[4]arene and some of its derivatives to form complexes with human serum albumin. Scope – bioorganic chemistry.