Design, synthesis and antiviral evaluation of novel conjugates of the 1,7,7-trimethylbicyclo[2.2.1]heptane scaffold and saturated N-heterocycles via 1,2,3-triazole linker.

A new series of heterocyclic derivatives with a 1,7,7-trimethylbicyclo[2.2.1]heptane fragment was designed, synthesised and biologically evaluated. Synthesis of the target compounds was performed using the Cu(I) catalysed cycloaddition reaction. The key starting substances in the click reaction were an alkyne containing a 1,7,7-trimethylbicyclo[2.2.1]heptane fragment and a series of azides with saturated nitrogen-containing heterocycles. Some of the derivatives were found to exhibit strong antiviral activity against Marburg and Ebola pseudotype viruses. Lysosomal trapping assays revealed the derivatives to possess lysosomotropic properties. The molecular modelling study demonstrated the binding affinity between the compounds investigated and the possible active site to be mainly due to hydrophobic interactions. Thus, combining a natural hydrophobic structural fragment and a lysosome-targetable heterocycle may be an effective strategy for designing antiviral agents.

Design of Conjugates Based on Sesquiterpene Lactones with Polyalkoxybenzenes by "Click" Chemistry to Create Potential Anticancer Agents.

Using the methodology of "click" chemistry, a singular method has been developed for the synthesis of unique conjugates based on sesquiterpene lactones: dehydrocostuslactone and alantolactone with polyalkoxybenzenes. To expand the structural range of the resulting conjugates, the length of the 1,2,3-triazole spacer was varied. For all synthesized compounds, the cytotoxic profile was determined on the cell lines of tumor origin (SH-SY5Y, HeLa, Hep-2, A549) and normal Hek 293 cells. It was found that the compounds based on alantolactone 7a-d with a long spacer and substances containing dehydrocostuslactone 10a-d with a short spacer have the greatest toxic effect. The decrease in cell survival under the action of these conjugates may be due to their ability to cause dissipation of the transmembrane potential of mitochondria and inhibit the process of glycolysis, leading to cell death. The obtained results confirm the assumption that the development of conjugates based on sesquiterpene lactones and polyalkoxybenzenes can be considered as a promising strategy for the search for potential antitumor agents.

Synthesis of camphecene derivatives using click chemistry methodology and study of their antiviral activity.

A series of seventeen tetrazole derivatives of 1,7,7-trimethyl-[2.2.1]bicycloheptane were synthesized using click chemistry methodology and characterized by spectral data. Studies of cytotoxicity and in vitro antiviral activity against influenza virus A/Puerto Rico/8/34 (H1N1) in MDCK cells of the compounds obtained were performed. The structure-activity relationship analysis suggests that to possess virus-inhibiting activity, the compounds of this group should bear oxygen atom with a short linker (C2-C4), either as a hydroxyl group (18, 19, 29), keto-group (21) or as a part of a heterocycle (24). These compounds demonstrated low cytotoxicity along with high anti-viral activity.

Novel class of functionalized ionic liquids with grafted CMPO-moieties for actinides and rare-earth elements recovery.

The general approach to a novel class of functionalized ionic liquids 4-6 bearing grafted diphenylcarbamoylmethylphosphine oxide complexing groups in the cation has been elaborated. The synthetic route comprises the preparation of the intermediate (diphenylphosphorylmethylcarbamoyl)propylimidazole 3, followed by sequential quaternization by alkyl halides (chlorides or bromides) and anionic exchange in the case of ionic liquids bearing the hexafluorophosphate anion. The structures of two ionic liquids were confirmed by X-ray analysis, revealing the strong intramolecular hydrogen bond formed by the acidic protons of the heterocycle and oxygen atom either of the P=O or C=O group, depending on the anion nature. In neutral media, these ionic ligands form complexes ML(2) with europium chloride or europium nitrate via an O,O-bidentate mode similar to known neutral CMPO compounds. The solid phase extractants prepared by immobilization of these FILs on solid matrixes possess sorption activity towards actinides and rare-earth elements in nitric acid solutions.

Electroencephalographic intercentral interaction as a reflection of normal and pathological human brain activity.

The authors summarized EEG findings and defined the nature of the intercentral EEG relationships in different functional states in healthy subjects and patients with organic cerebral pathology, based on a coherence analysis. Similar EEG characteristics in healthy individuals were identified: an anterior-posterior gradient of average coherence levels, the type of cortical-subcortical relationships in anterior cerebral structures. Right- and left-handed individuals showed frequent and regional differences in EEG coherence, which mainly reflected specificity of intracortical relationships. Development and regression of pathology in right-and left-handed individuals with organic brain lesions were thought to be caused by these differences. Lesions of regulatory structures (diencephalic, brain stem and limbic structures) provoked a more diffused kind of changes of intercentral relationships, in contrast to cortical pathology. These changes tended to reciprocate. The dynamic nature of intercentral relationships and their interhemispheric differences was revealed when changing functional states of the brain (increase and decrease of functional level) in healthy individuals and patients with organic cerebral pathology in the process of conscious and psychic activity restoration. Changing activity predominance of certain regulatory structures was considered one of the most important factors determining the dynamic nature of EEG coherence.