Towards carborane-functionalised structures for the treatment of brain cancer

Abstract

Boron neutron capture therapy (BNCT) is a promising targeted chemoradiotherapeutic technique for the management of invasive brain tumors, such as glioblastoma multiforme (GBM). A prerequisite for effective BNCT is the selective targeting of tumour cells with B-rich therapeutic moieties. To this end, polyhedral boranes, especially carboranes, have received considerable attention because they combine a high boron content with relative low toxicity and metabolic inertness. Here, we review progress in the molecular design of recently investigated carborane derivatives in light of the widely accepted performance requirements for effective BNCT.

A stable meta‐carborane enables the generation of boron‐rich peptide agonists targeting the ghrelin receptor

“…Different groups further developed closo ‐borane‐Tyr 3 ‐octreotate conjugates . Carboranes in particular are optimal boron compounds for conjugation owing to a high boron content and biological stability . Modification of [F 7 ,P 34 ]‐neuropeptide Y with 1,2‐dicarba‐ closo ‐dodecaborane ( ortho ‐carborane) for targeting the Y 1 receptor in breast tumors was previously described .…”

“…20,21 Carboranes in particular are optimal boron compounds for conjugation owing to a high boron content and biological stability. 22 Modification of [F 7 ,P 34 ]-neuropeptide Y with 1,2-dicarba-closododecaborane (ortho-carborane) for targeting the Y 1 receptor in breast tumors was previously described. 23,24 By this approach, a sufficient amount of boron for BNCT was internalized into receptorexpressing cells.…”

Carborane‐Based Analogues of 5‐Lipoxygenase Inhibitors Co‐inhibit Heat Shock Protein 90 in HCT116 Cells

“…Thus, ortho ‐carborane can be thermodynamically converted into meta ‐ and para ‐carborane at high temperatures . Their high boron content makes them suitable for boron neutron capture therapy (BNCT), a binary cancer therapy . For efficient treatment, a concentration of 20–35 μg of the isotope boron‐10 per gram of tumor is required .…”

“…[5] Their high boron content makest hem suitable for boron neutron capturet herapy (BNCT), ab inary cancert herapy. [6] For efficient treatment, ac oncentration of 20-35 mgo ft he isotopeb oron-10 per gram of tumor is required. [7] To ensure tumor-selective shuttlingo fh igh amounts of boron into tumor cells, carboranes have been used in combination with tumor-selective peptides for targeting the Y 1 [8] or ghrelin receptors.…”

Synthesis of Polyhedral Borane Cluster Fused Heterocycles via Transition Metal Catalyzed B-H Activation

“…Icosahedral carboranes are a class of carbon-boron molecular clusters with three dimensional aromaticity analogues to benzene, the features of high boron content, extraordinary thermal and chemical stability, and synthetic flexibility make the carborane derivatives be a kind of important building blocks in functional materials [1][2][3][4], key frameworks in pharmaceuticals [5][6][7][8] and ligands in organometallic chemistry [9][10][11][12][13]. Therefore, the selective functionalization of carboranes has attracted considerable interest from chemists [14][15][16][17][18].…”