Inhibition of glutathione S-transferases by photoactive calix[4]arene α-ketophosphonic acids.

Calix[4]arenes bearing photoactive α-ketophosphonic acid groups at the upper rim of the macrocycle were synthesized and evaluated as inhibitors of glutathione S-transferases. Irradiation at 365 nm increased the inhibition effects of some macrocyclic compounds on GSTP1-1 by more than two orders of magnitude. Calix[4]arene bis-α-ketophosphonic acids substituted at the lower rim by n-propyl or n-butyl groups showed IC50 values in the low micromolar range. Kinetics of the irreversible inhibition was described by pseudo-first-order rate constants dependent on inhibitor concentration. The values of second-order rate constants were higher for glutathione S-transferase from human placenta than for the enzyme from equine liver. Molecular docking suggested that photoactive macrocyclic compounds cover the active site of glutathione S-transferase, providing the possibility to modify the catalytically important amino acid residues during irradiation.

Calixarene-based phosphinic acids as inhibitors of protein tyrosine phosphatases.

In the present work, the derivatives of calix[4]arene, thiacalix[4]arene, and sulfonylcalix[4]arene bearing four methylene(phenyl)phosphinic acid groups on the upper rim of the macrocycle were synthesized and studied as inhibitors of human protein tyrosine phosphatases. The inhibitory capacities of the three compounds towards PTP1B were higher than those for protein tyrosine phosphatases TC-PTP, MEG1, MEG2, and SHP2. The most potent sulfonylcalix[4]arene phosphinic acid displayed Ki value of 32 nM. The thiacalix[4]arene phosphinic acid was found to be a low micromolar inhibitor of PTP1B with selectivity over the other PTPs. The kinetic experiments showed that the inhibitors compete with the substrate for the active site of the enzyme. Molecular docking was performed to explain possible binding modes of the calixarene-based phosphinic inhibitors of PTP1B.

Trapping of thermally generated ortho- and para-quinone methides by imidazoles and pyrazoles: a simple route to green synthesis of benzopyrone-azole hybrids and their evaluation as α-glucosidase inhibitors.

An efficient green approach for the trapping of in situ generated ortho-and para-quinone methide intermediates by imidazoles and pyrazoles has been developed. A wide range of quinone methide precursors based on simple phenols are compatible with the experimental protocol under mild thermal conditions. This methodology was demonstrated to be suitable for the synthesis of methylene-linked benzopyrone-azole hybrids using naturally occurring coumarin and chromone Mannich bases. In most cases, the products were isolated in good to excellent yields without chromatographic purification. In vitro studies showed that some of the synthesized compounds exhibit inhibitory activity towards α-glucosidase.