Effect of Glycyrrhetic Acid Derivatives on Regulation of Thymocyte Volume.

We studied the effects of glycyrrhetinic acid (bioactive aglycone of glycyrrhizin) and its ester derivatives at positions C-3 and C-30 on the cell volume regulation in rat thymocytes under conditions of hypoosmotic stress. Native glycyrrhetinic acid completely suppressed this process with half-maximal concentration of 12.7±1.4 µM and Hill coefficient of 3.1±0.6. Formation of esters at C-3 (esters with the acetic, cinnamic and methoxi-cinnamic acid) and at C-30 (methyl ester) drastically decreased the inhibitory activity of the molecule, suggesting that intact hydroxyl group at C-3 and carboxyl group at C-30 are structurally important determinants of biological activity of glycyrrhetinic acid towards volume regulation of thymic lymphocytes.

[The effect of ionic strength on reversible inhibition of catalytic activity of acetylcholinesterase by thione phosphonates]. / Vliianie ionnoi sily na obratimoe tormozhenie kataliticheskoi aktivnosti atsetilkholinésterazy tionfosfonatami.

The effect of ionic strength was used to analyze the mechanism of reversible acetylcholinesterase inhibition by three alkoxymethylthionphosphonates. The most considerable realization of the hydrophobic interaction with the surroundings of the enzyme esteratic site was marked for n-butyl derivative (compound I). The replacement of piperidine by morpholine (compound II) resulted in a decrease of the anticholinesterase activity by an order due to enhancement of the inhibitor hydrophilicity. An increase of MgCl2 concentration promotes an enhancement of the uncompetitive component contribution for compound III contrast to compound II. Hydrophobicity of the phosphoryl part of the compound I molecule is balanced under hydrophobic interaction of the heterocyclic "cationic head" with the enzyme anionic site. The break of this equilibrium intensifies the allosteric regulation, on the one hand, and lowers the inhibitor efficiency, on the other hand.