Laboratory for Redox-active Molecular Systems

Name of the project: Molecular design of redox-active heterocyclic systems - new antitumor agents

Research directions: Chemistry and chemical technology

Goals of project:

Developing a new methodology for the design of redox-active molecular systems, determining the correlation between their structure and properties, establishing the mechanisms of the antitumor action of such systems and creating highly efficient antitumor agents.

Project objective:

1. Creating a world-class interdisciplinary laboratory that will feature highly-qualified professionals in the field of organic, elemento-organic chemistry, biochemistry, biology and pharmacology. The laboratory will be aimed at solving problems of the molecular design of new highly-efficient antitumor agents.
2. Developing methods of the synthesis of new types of redox-active molecular systems that will include as a basis sterically hindered phenols that have a phosphorus-containing functional group that is responsible for the stability and redox-activity of generated methylene quinone, as well as an aza-heterocyclic substituents as a pH-sensitive component. Studying their physical and chemical properties (reduction-oxidation potential, photosensitivity etc.).
3. Developing methods for synthesizing pH-sensitive phosphorus-containing sterically hindered phenols (SHPs) that have additional fragments in the molecules, particularly, derivatives of benzofuroxan, isatin, dibenzo xanthene («hybrid» SHPs) capable of interacting with DNA as well as «vector» groups providing selective binding to DNA and (or) pathological proteins of a tumor cell; studying their physical and chemical properties (redox potential, photosensitivity etc.)
4. The research of the potential antitumor activity of the produced compounds will include: a study of the cytotoxic profile on a panel of normal and tumor cell lines and determining the selectivity of their action; determining the mechanisms of cytotoxic action on the basis of an understanding of the pathological processes in oncogenesis; conducting an analysis of the «structure-activity» correlation to determine leading compounds for the study of antitumor activity in vivo using experimental model animals with grafted tumor. Moreover, on the basis of the accumulated data we will optimize the structures of synthesized compounds to achieve the highest selectivity and biological effect. Since many antitumor agents whose action is based on interaction with DNA (antineoplastic agents, cytostatics) also demonstrate antimicrobial capabilities, we will additionally study the antibacterial and antifungal activity of the produced compounds, including against resistant strains of microorganisms that pose serious danger to people all over the world.