ИСТИНА

Проект направлен на получение борсодержащих производных 9-аминоакридина (ДНК-интеркаляторов) для лечения онкозаболеваний методом бор-нейтронозахватной терапии рака (БНЗТ). В долгосрочной перспективе целью представленного проекта является создание научных предпосылок для адресной доставки борсодержащего компонента в раковые клетки и лечения онкозаболеваний методом БНЗТ, что обеспечит увеличение продолжительности жизни и снижение смертности населения от социально-значимых заболеваний.

The project is aimed at solving the problem of creating boron-containing biologically active compounds that can be used for boron neutron capture therapy for cancer (BNCT). One of the ways to solve this fundamental problem is the creation of acridine-based boron-containing DNA intercalators containing a large number of boron atoms and capable of selectively accumulating in cancer cells, which is one of the key requirements of BNCT. It is known that acridines are characterized by a flat and hydrophobic structure, due to which they are able to interact with various biomolecular targets. These properties are mainly attributed to the efficiency of the π-conjugated structure for intercalation between double-stranded DNA. Therefore, the goal of this project is to develop effective methods for the synthesis of new conjugates of polyhedral boron hydrides with acridine. To achieve this problem, it is proposed to use the CuI-catalyzed [3+2]-dipolar cycloaddition of alkynes to azides. Varying the size and charge of the boron cluster, as well as the length and hydrophilicity/lipophilicity of the spacer between the boron core and the functional part of the molecule will be used to create a library of boron-containing acridines of various structures. In order to establish the structure-property relationship in a series of new boron-containing acridines, within the framework of the presented project, their cytotoxicity and ability to integrate into the DNA molecule will be studied. Preparation, study of cytotoxicity and ability to bind to DNA of acridine derivatives based on cobalt/iron bis(dicarbollide) and closo-dodecaborate anion, provided by this project, are topical tasks that have not been previously set for these objects by anyone. The scientific novelty of the project lies in the fact that when it is carried out, for the first time, it is supposed to obtain acridine derivatives modified with cobalt/iron bis(dicarbollide) or closo-dodecaborate anion at the N9 position of the aromatic system. Currently, only a single group of boron-containing derivatives of acridine is presented in the literature - its conjugates based on para-carborane. However, the data published to date on these derivatives do not allow a reliable correlation between the structure of boron-containing acridine and its biological activity, and as a result of the proposed project, this gap will be filled. It is assumed that in the course of the project implementation qualitatively new results, not inferior to the world level, will be obtained that can make a significant contribution to the development of the chemistry of polyhedral boron hydrides. The introduction of cobalt/iron bis(dicarbollide) and closo-dodecaborate anion into the structure of biomolecules is of great interest from the point of view of the development of boron neutron capture therapy (BNCT) for cancer. The combination of the unique structure of polyhedral boron hydrides, extensive possibilities for their functionalization (in order to create a range of practical properties) using the methods and techniques developed by the project manager creates the prerequisites for the successful implementation of the project and the creation of a competitive advantage in this area. Development of methods for the synthesis of new derivatives of closo-dodecaborate anion and bis(dicarbollide) cobalt/iron based on acridine lays the foundation for the creation of an innovative drug for BNCT of malignant neoplasms.