The bioinorganic and medicinal chemistry of carboranes: from new drug discovery to molecular imaging and therapy

Abstract

The role of carboranes in medicinal chemistry has diversified in recent years and now extends into areas of drug discovery, molecular imaging, and targeted radionuclide therapy. An introduction to carborane chemistry is provided to familiarize the non-expert with some key properties of these molecules, followed by an overview of current medicinally-orientated research involving carboranes. The broad-ranging nature of this research is illustrated, with emphasis placed on recent highlights and advances in this field.

Metallacarboranes and their interactions: theoretical insights and their applicability

“…Both topics have been mentioned in several recent reviews on the medicinal chemistry of carboranes, 60,65,66 or enzyme inhibition 67 and the latter is also treated in much detail in a book chapter. 64 The best established role of boron-based compounds in medicine is as agents for the boron neutron capture therapy (BNCT) of cancer.…”

“…Metallacarboranes have recently been arousing a growing interest for their potential to be used in medicinal chemistry as novel pharmacophores or radioimaging agents. 2,52,60 The versatility of metallacarboranes is given by both the wide array of the existing carborane cages used as ligands and the possibility to utilize a large variability of (transition) metal ions. In this manner, the shape and charge of the metallacarboranes can be tailored to specific aims.…”

Dicarba-closo-dodecarborane-containing half-sandwich complexes of ruthenium, osmium, rhodium and iridium: biological relevance and synthetic strategies

“…26 Thus, while the normal endothelial layer surrounding the blood 50 vessels feeding healthy cells restricts the amount of constituents necessary for cell replication (amino acids and nucleic acid precursors for example), the endothelial layer of blood vessels in diseased tissues allows an elevated quantity of such cell constituents to enter the cells. 23, 27 Another 55 strategy is to attach the borane cluster to tumour antibodies that can target specific cell types. 28 A third approach is to use nano-containers such as lipoproteines and liposomes.…”

“…23,47 Docking simulations have also been performed 48 as well as in vivo experiments that demonstrate that the administration of such compounds to estrogen-deficient mice prevents bone loss as 25 effectively as administration of 17β-estradiol. 23 Retinoic acid is a natural metabolite of vitamin A that is involved in the regulating the development of normal and tumoral epithelial cells in various tissues. 49 The utilisation of 30 retinoic acid as a clinical drug for the treatment of acute promyelocytic leukemia has been recently approved.…”

“…In the meantime, an ER deficiency leads to a loss of bone mass due to the estrogenic regulation of bone maintenance. 23 Thus many efforts are focused on the synthesis of ER agonists and antagonists.…”