Karborany jako lipofilowe farmakofory

Carboranes are boron cage systems in which one or more carbon atoms belong as an integral part to an elektron-delocalized borane framework. They are characterized by high boron content, remarkable thermal and chemical stability, spherical geometry and high hydrophobicity. Electropositivity of boron enables BH groups in carboranes to form unconventional hydrogen bonds defined also as proton - hydride bond. Another type of interaction was found for CH group of carborane - participating in hydrogen-bonded complexes, although these complexes are approximately 21 kJ/mol less stable than complexes formed by BH groups [2-8]. Proton - hydride bonds are formed mainly due to electrostatic interactions between boron--bound hydrogen atom bearing partial negative charge and hydrogen atom of a biomolecule bearing partial positive charge. It was found that carboranes forms proton - hydride bonds with biomolecules preferably with BH groups of the cage opposite to the carbon atom. Carboranes have been used as hydrophobic pharmacophores in design of analogues of biologically active compounds such as estradiol, retinoic acids, protein kinase C modulators and TNF-a activity modulators. Some of these carbo-rane containing biomolecules interact effectively with the corresponding receptor enzymes exhibiting equal or even higher biological activity than their endogenous counterparts and are characterized by remarkable resistance to catabolism.