Search for structure-antimicrobial activity correlation of selected groups of boraheterocyclic compounds

Organic boron compounds play an increasingly important role due to their usefulness in various fields of science. Currently, they are widely used in modern synthesis as convenient and readily available substrates for the preparation of complex organic molecules with specific properties, including drugs or conductive polymers. Currently, more and more hopes are associated with the study of biological properties and the direct application of boron compounds in medicine. An example is the Boron-Neutron Capture Therapy (BNCT) anti-cancer therapy. In recent years, great interest among researchers has aroused in benzoxaboroles - a group of boracyclic compounds, the molecules of which are composed of condensed rings: benzene and the five-membered ring of oxaborole composed of, among others, from boron and oxygen atoms. It has been found that some benzoxaborole derivatives exhibit high antifungal, antibacterial, antiparasitic and anti-inflammatory activity, and at the same time they are not very toxic. Potential applications of these compounds relate to the treatment of important diseases such as African sleeping sickness, malaria and fungal infections. Recently (July 2014), one of these compounds (Tavaborole AN2690, trade name of the preparation Kerydin) has been approved for use in the treatment of onychomycosis. A little later, another compound (Crisaborole, trade name for Eucrisa) was introduced for the treatment of atopic dermatitis. Another boraheterocyclic compound with high antibacterial activity is Vaborbactam - an inhibitor of enzymes that break down carbapenems, "last-chance antibiotics". It has been approved for the treatment of severe, complicated urinary tract infections caused by Enterobacteriaceae. In clinical trials, there are other compounds with a similar chemical structure showing activity against Gram-negative rods, which is another argument for the advisability of further research on this type of substances. This project concerns the synthesis and testing of the properties of selected groups of boracyclic compounds containing a boron atom in one of the rings (additionally fused with an aromatic ring).

An important part of the project concerns the assessment of their antimicrobial activity (killing against bacteria and yeast-like fungi). It should be strongly emphasized that research aimed at developing new classes of biologically active substances with antibacterial and antifungal properties is becoming increasingly important. This is due to, inter alia, from the growing resistance of bacterial strains to currently used antibiotics. It is also planned to investigate the properties of the obtained compounds as inhibitors of enzymes responsible for bacterial resistance to drugs and as inhibitors of membrane pumps that remove substances harmful to bacteria from the cell, including antibiotics. We recently obtained preliminary, promising results on the biological properties of synthesized compounds containing silicon and oxygen atoms in the boracyclic ring. Therefore, it is worth not only continuing but also extending this work, especially in the areas related to medical and bioanalytical chemistry. These studies would also include compounds with a similar structure containing, inter alia, a phosphorus atom in a boracyclic ring.