Crystal structure of diethyl {2,2,2-tri-chloro-1-[2-(1,3-dioxo-2,3-di-hydro-1H-isoindol-2-yl)-4-methyl-pentanamido]-eth-yl}phospho-nate.

In the title phospho-rylated compound, C20H26Cl3N2O6P, the phthalimide unit is essentially planar (r.m.s. deviation = 0.0129 Å) and the O atoms of this unit deviate from the mean plane by 0.080 (3) and 0.041 (3) Å. In the crystal, pairs of mol-ecules are linked by N-H⋯O and weak C-H⋯O hydrogen bonds involving the same acceptor atom, forming inversion dimers. In addition, π-π stacking inter-actions between the phthalimide groups, with a centroid-centroid distance of 3.7736 (13) Å, and further weak C-H⋯O hydrogen bonds connect the inversion dimers into columns along [01].

QSAR studies and antimicrobial potential of 1,3-thiazolylphosphonium salts.

The regression QSAR models were built to predict the antimicrobial activity of new thiazole derivatives. Compounds with high predicting activity were synthesized and evaluated against Gram-positive and Gram-negative bacteria and fungi. 1,3-Thiazole-4-ylphosphonium salts 4 and 5 displayed good antibacterial properties and high antifungal activity. The predictions are in a good agreement with the experiment results, which indicate the good predictive power of the created QSAR models.

Synthesis, biological evaluation and docking of novel bisamidinohydrazones as non-peptide inhibitors of furin.

A series of novel non-peptidicfurin inhibitors with values of inhibitory constants (Ki) in the range of 0.74-1.54 µM was obtained by interactions of aminoguanidine hydrocarbonate with three diaryldicarbalde- hydes. Correspondingly p-hydroquinone, piperazine and adipic acid were used as linkers between their ben- zene moieties. Docking studies of these new inhibitors into recently published 3D-structure of human furin (PDB code 4OMC) showed that they were able to interact with subsites S1 and S4 of the enzyme. The overall arrangement of bisamidinohydrazones into furin active site was similar to the position of the ligand co- crystallized with a protease. Observations obtained with molecular modeling allowed further guidance into chemical modifications of the synthesized inhibitors which improve their inhibitory activity.

[Non-peptide furin inhibitors based on amidinohydrazones of diarylaldehydes].

A series of novel non-peptidic furin inhibitors containing amidinohydrazone moieties has been synthesized under interaction of dialdehydes, the derivatives of ethylene diethylvanillin ethers, with aminoguanidine bicarbonate. Two aryl cycles were bridged by 1,2-ethylene-, 1,4-buthylene- or 1,4-dimethylenebenzene-group. The compounds have been found to inhibit furin. The antifurin activity was shown to grow with the increase of the length and/or hydrophobicity of the bridge. The most potent compound, containing in the bridge the lypophylic benzene cycle was found to inhibit the activity of furin with Ki = 0.51 microM.

[Participation of proteinkinase CK2 in regulation of human erythrocytes plasma membrane redox system activity: relative contribution of ca(2+)-dependent and ca(2+)-independent mechanisms of its activation].

Involvement of protein kinase CK2 (2.7.11.1) in modulation of live cells trans-plasma membrane electron transport was first discovered. Using human erythrocytes a decrease of plasma membrane redox system (PMRS) activity is shown under the action of specific protein kinase CK2 inhibitors. Using inhibitory analysis the activity regulation of human erythrocytes PMRS by Ca(2+)-dependent and Ca(2+)-independent mechanisms were investigated. It was shown that functional Ca(2+)-antagonists (nitrendipine and calmidazolium) significantly increased, and functional Ca(2+)-agonists to some extent reduced or did not affect the trans-plasma membrane electron transport in these cells.

[Study on derivatives of 5-amino-4-acylamino-1H-pyrazole as inhibitors of furin].

A series of 5-amino-1H-pyrazoles was synthesized and studied as inhibitors of furin. The most potent compound, 5-amino-4-acetylamino-3-(4-methylphenylamino)1H-pyrazole, was found to retard the activity of furin by mixed-type inhibition with K = 288 microM. These findings permit to plan new ways for chemical modifications of the 5-amino-1H-pyrazole structure and design more potent furin inhibitors of non-peptide nature.