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A copper-promoted reductive homocoupling reaction, for the first time used for a metal complex, allowed obtaining a new kind of complexes with the encapsulated metal ions, C-C conjugated bis-clathrochelates. These compounds demonstrate extremely high transcription inhibition activity in the T7 RNA polymerase system with values of IC50 reaching as low as the submicromolar range, which places them among the most potent metal-based transcription inhibitors.

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In this review we have summarized the results of our recent research on telomerase inhibitors and G-quadruplex DNA ligands. A series of potential enzyme inhibitors were synthesized and studied. These compounds were based on tricyclic heteroaromatic systems (thiazolobenzimidazoles phenazines, acridones), amino-substituted cyanines and natural and synthetic porphyrins and their metalocomplexes. A number of compounds, including cyanines and especially porphyrin derivatives and conjugates, were found to efficiently inhibit telomerase at low micromolar concentrations in the in vitro TRAP assay. Porphyrins demonstrated antiproliferative activity in tumor cell cultures at micro- and nanomolar concentrations. Spectral-fluorescent and electrophoretic experiments were performed to investigate the interaction of ligands with duplex and quadruplex DNA, and in many cases binding mode was established. Convenient G-octet model of G-quadruplex was developed to study the ligand-target binding using quantum-chemical methods. QM/MM hybrid approach ONIUM2 was employed to model the interaction of small molecules with Tel22 quadruplex DNA

To enlarge a spectrum of biologically active compounds in the series of the 1,2,4-triazino[5,6-b] [1,4]benzothiazine (1,2,4-TBT) derivatives and reveal among them efficient inhibitors of RNA synthesis Methods. The methods of structure optimization of the 3-oxo-1,2,4-TBT by fragment-oriented substitution, the molecular doking of new structures in a virtual target, the rational chemical synthesis of the theoretically predicted compounds and their testing in the system of transcription in vitro. Results. The series of 1,2,4-TBT derivatives with substituents in the benzene and triazine cycles of a base molecule were synthesized. The testing of synthesized compounds in the in vitro transcription system directed by T7 RNA polymerase revealed the structure-and concentration dependent inhibition of the RNA synthesis by some of these compounds. The experimental and virtual screening data for all investigated compounds have a good correlation. It was found that most effective derivative is the 3-oxo-8-butyl-1,2,4-TBT which completely inhibited transcription at the concentration of 6 mg/ml. Conclusions. The biotesting results allow us to assume that the inhibition of RNA synthesis is caused by binding of the 3-oxo-8-butyl-1,2,4-TBT to both free RNA polymerase molecules and those including in a transcriptional complex with DNA.

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A bacterial strain IMBG1S6 producing exopolysaccharide (EPS) was isolated from siliceous rock and identified as a Paenibacillus species by partial sequencing its 16S rDNA. Paenibacillus sp. IMBG156 was used in a novel technology for inoculant production based on co-cultivating this bacterium with any bacterium of choice. Paenibacillus sp. provides in situ the bacterial cells of the inoculant with EPS, a carrier, and most likely with a source of carbon and energy. The partner bacterium designates a type of inoculant (biopesticide or biofertiliser). The strain IMBG156 does not destroy the signaling system of Gram-negative partners, based on acylated homoserine lactones, stimulates plant growth, and is rather competitive in the plant rhizosphere and soil. A prototype of the inoculant based on dual-culturePaenibacillus sp. IMBG156 -Pseudomonas sp. IMBG163 exhibits a noticeably longer shelf life than monoculture of Pseudomonas sp. IMBGI63.