Carbaboranes – more than just phenyl mimetics

Abstract

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, [F7, P34]-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 Bpa32 (Bpa=benzoylphenylalanine) in the reduced-size NPY analogue [Pro30, Nle31, Bpa32, Leu34]-NPY 28–36 by ortho-carbaboranyl propanoic acid. The inclusion of the carbaborane derivative resulted in a short NPY agonist with an interesting hY2R/hY4R preference. This might be a promising approach in the field of anti-obesity drug development.

Modular triazine-based carborane-containing carboxylic acids – synthesis and characterisation of potential boron neutron capture therapy agents made of readily accessible building blocks

“…highly stable peptide bond between the carboxylic acid of boron-rich derivatives and an amino group of the biomolecule of interest (e.g. lysine in specific peptides) is a much-favoured coupling strategy 20,48,[50][51][52][53] and was also employed here for the thioglycolic acid derivative 4. Compound 4 could be incorporated up to three times into the breast cancer-selective peptide [F 7 ,P 34 ]-NPY at positions 4, 18 and 22.…”

In Vitro Cytostatic Effect on Tumor Cells by Carborane‐Based Dual Cyclooxygenase‐2 and 5‐Lipoxygenase Inhibitors

“…[29,[32][33][34] Since the volume of carboranes is slightly larger than a rotating benzene ring, they can be described as three-dimensional benzene analogues. [28,35] Besides their hydrophobic nature, which is beneficial for enhanced cell membrane penetration, multiple noncovalent interactions, like dihydrogen bond formation, may increase the affinity to biological targets, including enzymes or receptor proteins. [27,34,36] Thus, carboranes are frequently used to mimic substituted or unsubstituted phenyl groups.…”

Modulation of γ-Secretase Activity by a Carborane-Based Flurbiprofen Analogue

“…Thus, ortho -carborane can be thermodynamically converted to meta - and para -carborane at high temperatures [ 24 , 25 ]. Due to the fact of their remarkable stability and hydrophobicity, a growing interest in carboranes for medicinal chemistry applications is becoming evident [ 26 , 27 , 28 , 29 , 30 , 31 , 32 , 33 , 34 ]. Although the first use of carborane derivatives in boron neutron capture therapy (BNCT) dates back to the 1950s [ 35 ], it was only in 2009 that Hawkins et al showed conclusively that a carborane derivative, namely, a neutral rhenacarborane, can cross the BBB [ 36 ].…”