Current status. Nowadays, polyhedral heteroboranes are unique objects of intense research. A subset of this extensive class of compounds are carboranes having the general formula C₂B₁₀H₁₂. Since the discovery of carboranes in 1963 various applications have been found in catalysis [1], materials design [2], and medicine [3,4]. Over the past decade, there has been an increasing interest in the use of carboranes as pharmacophoric units in drug design. The role of carboranes in medicinal chemistry extends into areas of drug discovery, molecular imaging, targeted radionuclide therapy [5], chemo therapy [6], and boron-neutron capture therapy (BNCT) [3-6].

At present, the clinical practice of BNCT relies on two preparations: 4-dihydroxy borophenyl alanine [8-10], and mercapto-closo-dodecaborate sodium [8], and many other boron delivery agents are under evaluation. Nitroaromatic compounds have antitumor [11], antiviral activity [12] and are used in cancer chemotherapy [13]. Various coumarin derivatives are used in clinical practice, mainly as anticoagulants, however, synthesis and investigation of coumarin-hybrids is an actual task today since they have a wide range of therapeutic activity: antioxidants, anti-inflammatory, antitumor, MAO-B inhibitor, antimicrobial and antimalarial [14-16]. Multifunction activity of these hybrid compounds makes them as potential candidates for treatment of multifactorial diseases such as cancer, Alzheimer's disease, metabolic syndrome, AIDS, malaria, and cardiovascular diseases.

Our earlier in vivo studies of anticancer activity of the synthesized carboranyl containing compounds, demonstrating the potential effectiveness of proposed drugs, have shown that the index of tumor growth inhibition of 1-(2',4'-dinitrophenyl)-2-phenyl-2-(methyl-o-carboranyl)-ethane for Walker carcinosarcoma (82%), Sarcoma-1 (76%), Pliss lymphosarcoma (65%). Ethyl 1-nitro-2-phenyl-2-(phenyl-o-carboranyl) propionic acid showed activity against Walker carcinoma sarcoma ( 82%), lymphosarcoma Plissa (59%) [17]. At the same time, these compounds contain a large amount of boron, and have low toxicity (1-nitro-2-phenyl-2-(phenyl-o-carboranyl) propionic acid LD₅₀ = 3450 mg/ kg [18], and for example, cytotoxicity studies of 2-(p-methoxybenzylidene) -3-(phenyl-o-carboranyl)hydrindone showed LD₅₀ = 5640 mg/ kg, which also meets requirements for BNCT preparations.

In the present project proposes to synthesize and study the chemical and biological activity of nitro compounds [17,19-21], coumarins [22,23], hydrindons [24], saccharides nitrogen-containing derivatives [25,26] which are containing carborane nucleus. Synthesis and study of hybrids analogs of carborane and coumarins, nitro derivatives, hydrindons were not carried out so far. And this investigation is unique. Moreover, we are planning to be pioneers in use of magnetic metal nanostructures as carriers for targeted delivery of carborane compounds.

Thus, this Project aims to synthesis and investigation of effective carborane-containing broad-spectrum drugs, including anticancer activity.

The project’ influence on progress in this area. In case of success, it will contribute to the boron chemistry and biological activity of boron-containing compounds. In the long term it will develop boron neutron capture therapy of cancer, by synthesis of new potential effective agents based on carboranes. Moreover, we are planning to be pioneers in use of magnetic metal nanostructures as carriers for targeted delivery of carborane compounds.

Meeting the ISTC goals and objectives.

- The Project give opportunities to «weapon» scientists and engineers in INP to redirect their talents to peaceful activities.

- The Project will allow to collaborate with one of the leading scientists in the field of molecular design and synthesis Win Dehaen, Katholieke University Leuven. It also contributes to the relations between the Institute of Nuclear Physics and the National Center for Biotechnology.

- Supporting of basic and applied research in technology areas: drug discovery, basic and synthetic Chemistry.

- This project contributes to solve problem of searching for effective new drugs with broad-spectrum of activity, include anticancer.

Scope of activities. The following activities will be implemented under the Project: