What we develop

The central chemical core is vindeburnol, a synthetic derivative inspired by eburnamine-vincamine alkaloids. Medicinal chemistry work is focused on fine-tuning this core and identifying a molecule that improves memory and reduces depression-like behavior. Lead selection includes in vitro ADME-T studies, blood-brain barrier permeability assessment, and biochemical analysis of monoamine levels in brain regions.To elucidate the lead compound's mechanism of action, we plan to conduct receptor binding assays. The project is being carried out in collaboration with the V. Serbsky National Medical Research Center for Psychiatry and Narcology and with financial support from "R-Pharm".

Cancer is one of the leading causes of death worldwide. It is known that cancer cells eventually develop resistance to existing drugs. To address this issue, it is necessary to develop next-generation inhibitors and improve combination therapies. The project aims to discover and develop a safe and effective drug candidate based on a thiophene scaffold for the treatment of a specific type of cancer. We employ NCI60 screening to conduct early-stage studies on the structure-activity relationship of the chemical class under investigation.Certain molecules from our laboratory's library inhibit the growth of melanoma and central nervous system cancer cells by up to 85% in vitro. We are currently profiling protein kinase inhibitors and conducting in vitro ADME-T studies to select the most promising molecules for in vivo toxicity and efficacy testing. The project is being conducted in partnership with Collaboration Pharmaceuticals (USA).

Dispirotripiperazines are tricyclic molecules featuring two shared atoms, or "spiro-atoms." A distinctive structural feature of these compounds is the presence of two positively charged nitrogen atoms; the precise significance of these atoms is not yet fully understood and forms part of the focus of our research. It is hypothesized that these atoms facilitate electrostatic interactions with negatively charged heparan sulfate residues on the host cell surface, thereby preventing viruses from entering the cell to replicate. The PDSTP molecule—the most potent representative of this chemical class to date—inhibits, in vitro, a range of known viruses that utilize heparan sulfate to interact with host cells. It has recently demonstrated efficacy in rabbit models of herpetic keratitis. This research is being conducted in the UK in collaboration with Charité – Universitätsmedizin Berlin and the University of Cagliari.

Inspired by interesting pharmacological compounds containing the thieno[2,3-d]pyrimidine scaffold, we decided to investigate this chemical class against M. tuberculosis. Structure-activity relationship studies led to the identification of TP053 compounds, which exhibit low minimum inhibitory concentration values ​​against both replicating (H37Rv) and non-replicating (ss18b) forms of M. tuberculosis. TP053 acts as a prodrug against Mtb H37Rv through activation by the mycothiol-dependent nitroreductase Mrx2. The transformation of TP053 involves the condensation of the fused thiophene ring and the release of nitric oxide, an agent long known to be active against non-replicating forms of Mtb. At the same time, the resulting highly reactive metabolite exhibits activity against replicating mycobacteria. This project is being carried out in collaboration with the University of Pavia (Italy).

We have long been interested in the development of effective anti-tuberculosis drugs. In 2007–2008, working with several team leaders and with financial support from the commission, we discovered the class of benzothiazinones as potent anti-tuberculosis agents. Molecules of this class served as chemical probes for the discovery of a new target in the tuberculosis bacillus—the enzyme decaprenylphosphoryl-β-D-ribose-2'-epimerase (DprE1), which plays a key role in mycobacterial cell wall synthesis and, consequently, in bacterial growth. During the optimization of the hit compound BTZ043, the lead compound PBTZ169 was developed. This molecule exhibits greater in vitro activity against multidrug-resistant and extensively drug-resistant M. tuberculosis strains, as well as other isolates. PBTZ169—which was assigned the INN "macozinone" in 2018—has demonstrated safety and efficacy not only in animal models (preclinical studies) but also in human trials (NCT03423030, NCT03036163, NCT03776500, NCT04150224, NCT03334734).