Carbaboranes - more than just phenyl mimetics

Dicarba-closo-dodecaboranes(12) (C2B10H12, carbaboranes) are highly hydrophobic and stable icosahedral carbon-containing boron clusters. The cage framework of these clusters can be modified with a variety of substituents, both at the carbon and at the boron atoms. Substituted carbaboranes are of interest in medicine as boron neutron capture therapy (BNCT) agents or as pharmacophores. High and selective accumulation in tumour cells is an important requirement for a BNCT agent and is achieved by incorporating boron-rich, water-soluble carbaborane derivatives into breast tumour-selective modified neuropeptide Y, [F-7, P-34]-NPY. Preliminary studies showed that the receptor binding affinity and signal transduction of the boron-modified peptides were very well retained. Use of carbaboranes as pharmacophores was shown by replacement of Bpa(32) (Bpa = benzoylphenylalanine) in the reduced-size NPY analogue [Pro(30), Nle(31), Bpa(32), Leu(34)]-NPY 28-36 by ortho-carbaboranyl propanoic acid. The inclusion of the carbaborane derivative resulted in a short NPY agonist with an interesting hY(2)R/hY(4)R preference. This might be a promising approach in the field of anti-obesity drug development.