Boron Chemistry for Medical Applications

Abstract

Boron compounds now have many applications in a number of fields, including Medicinal Chemistry. Although the uses of boron compounds in pharmacological science have been recognized several decades ago, surprisingly few are found in pharmaceutical drugs. The boron-containing compounds epitomize a new class for medicinal chemists to use in their drug designs. Carboranes are a class of organometallic compounds containing carbon (C), boron (B), and hydrogen (H) and are the most widely studied boron compounds in medicinal chemistry. Additionally, other boron-based compounds are of great interest, such as dodecaborate anions, metallacarboranes and metallaboranes. The boron neutron capture therapy (BNCT) has been utilized for cancer treatment from last decade, where chemotherapy and radiation have their own shortcomings. However, the improvement in the already existing (BPA and/or BSH) localized delivery agents or new tumor-targeted compounds are required before realizing the full clinical potential of BNCT. The work outlined in this short review addresses the advancements in boron containing compounds. Here, we have focused on the possible clinical implications of the new and improved boron-based biologically active compounds for BNCT that are reported to have in vivo and/or in vitro efficacy.

Fused 1,2-Diboraoxazoles Based on closo-Decaborate Anion–Novel Members of Diboroheterocycle Class

“…Varying the structure of the boron cage and the nature of exo -polyhedral substituents, one can create molecules with plenty of useful properties such as high thermodynamic stability [ 7 , 8 ], magnetic properties [ 9 ], and low toxicity [ 10 , 11 , 12 ]. These properties cause a lot of boron cluster potential application in medicine [ 13 , 14 , 15 ], catalysis [ 16 , 17 ], the creation of luminescent materials [ 18 , 19 ], and in supramolecular chemistry [ 20 , 21 ].…”

In vitro and in vivo BNCT investigations using a carborane containing sulfonamide targeting CAIX epitopes on malignant pleural mesothelioma and breast cancer cells

“…They permit to reach a boron concentration ratio between tumour and normal tissues in the range of 3–5. Nevertheless, it is known in the BNCT research community that an improvement of the selective uptake of boron containing agents into the targeting tumour cells is necessary to increase the number of clinical use of BNCT 31 – 34 . In this contesxt, our group recently developed a macromolecular dual MRI/BNCT agent able to deliver to mesothelioma cells a therapeutic dose of boron (26 μg/g), significantly higher than in the surrounding tissue (3.5 μg/g) by exploiting overexpressed Low Density Lipoproteins (LDL) receptors 35 .…”

Carborane‐Containing Matrix Metalloprotease (MMP) Ligands as Candidates for Boron Neutron‐Capture Therapy (BNCT)

“…[1] In BNCT, a drug containing 10 B atoms is transported into tumor cells and then irradiated with thermal neutrons. [2] Thereupon, a 10 B nucleus absorbs a neutron to form an excited 11 B nucleus that decays through fission, emitting an α-particle ( 4 He 2 + ) as well as a 7 Li 3 + ion, both with high kinetic energy. The highly charged particles have a range of only about one cell diameter (5-9 μm) which limits the radiation damage to the cancer cell in which they arise, thus avoiding damage to the surrounding healthy tissue.…”

“…[5] Boroncontaining agents designed for neutron capture therapy have recently been reviewed. [1] Boron agents have played an increasingly important role in medical applications, [7] and recent literature reports of BNCT agents include a membrane-permeable boron cluster that was developed using the cell-penetrating lipopeptide pepducin as the vehicle for intracellular delivery of boron clusters. [8] Cellular uptake has been evaluated for pentagamaboronon-0 (PGB-0) to treat breast cancer with BNCT.…”