The aim of the project was to study of the “structure - properties - molecular mechanism of action” relationship for new potential ligands of benzodiazepine and fibrinogen receptors, which are promising medical neurotropic drags for the prevention and treatment of psychoneurotic disorders and potential antiaggregative agents for the prevention and treatment of cardiovascular diseases.

Teams of the Institute of Applied Physics and Physico-chemical institute synthesized and investigated the structure, conformational features, the nature of intermolecular interactions in the crystal, and affinity of the novel ligands of the benzodiazepine and fibrinogen receptors and their pharmacological properties.

The relevance of the project was determined by the importance and potential of 3-substituted dihydro-1,4-benzodiazepine as neurotropic and psychotropic drugs and ligands of fibrinogen receptor (integrin α_IIbβ₃) as inhibitors of platelets aggregation, which can be used for the prevention and treatment of dangerous cardiovascular diseases such as atherosclerosis, stenocardia, myocardial infarction, stroke and thromboembolism.

The new derivatives of 1,2-dihydro-1,4-benzodiazepines and new antagonists of αIIbβ3 derivatives of 1,2,3,4-tetrahydroisoquinoline, phthalimidine and quinazoline were studied.

The team of the Institute of Applied Physics, carried out the structural and conformational analysis, and investigated the peculiarity of intermolecular interactions of the compounds by X-ray single crystal structural analysis and calculated the mapping of electrostatic potential distribution on surface accessible area of the molecules. The synthesis and study of the affinity of 1,2-dihydro-4-benzodiazepines to the central benzodiazepine receptors and derivatives of 1,2,3,4-tetrahydroisoquinoline, quinazoline and phthalimidine to the α_IIbβ₃ fibrinogen receptor, the implementation of molecular docking antagonists to fibrinogen receptor and pharmacological study of the compounds were executed by the team of Physico-Chemical Institute. Understanding of structural factors contributing to the manifestation of the high affinity of these compounds to receptors will allow perform molecular design and synthesis of high-affinity compounds, which will extend the library of drugs, including import substitution.

Project team (Rep. of Moldova):

• Victor Kravtsov, Ph.D., head,
• Pavlina Bourosh, Ph.D.,
• Marina Fonari, Ph.D.,
• Lilia Croitor, Ph.D.,
• Elena Melnic,
• Olga Botezat.

Ukrainian partner - researchers from A. V. Bogatsky Physico-Chemical Institute of the National Academy of Sciences of Ukraine (NASU), head - Serghei Andronati, acad. NASU.