Medicinal Chemistry of Boron-Bearing Compounds for BNCT- Glioma Treatment: Current Challenges and Perspectives

Abstract

Since its first description, boron neutron capture therapy (BNCT) was a special type of radiotherapy for treatment of cancer and with focus mainly on glioma therapeutic. This procedure requires the selective accumulation of boron into the tumoral cells, and due to this requirement, different boron-enriched compounds have been designed and developed. Efforts to circumvent the selectivity-uptake challenge and other problems, such as solubility, stability, and toxicity, have been to driving force behind the medicinal chemistry field in boron-based compounds. In this regard, a wide diversity of medicinal chemistry hypothesis has been used to obtain new and efficient potential BNCT-glioma drugs. In this chapter, these ideas are analyzed focusing on their medicinal chemistry characteristics.

EGFR-Targeted Cellular Delivery of Therapeutic Nucleic Acids Mediated by Boron Clusters

“…For BNCT to be successful, the boron agent must meet the most important conditions, namely selective uptake by tumor tissue compared to normal tissue (preferably accumulation in the specific substructure of tumor cells) with ideal tumor-to-normal tissue and tumor-to-blood ratios of 2.5:1 and 5:1, respectively. Another important factor is a rapid excretion of boron compounds from blood and healthy tissue [ 49 ]. For this reason, we evaluated the ability of carrier-free uptake of antisense oligonucleotide conjugated with 5 metallacarboranes (FESANs) residues (B-ASO) directed toward mRNA of EGFR [ 24 ] by inductively coupled plasma mass spectrometry analysis (ICP MS).…”

Method of Measuring High-LET Particles Dose

“…The last two doses are due to that abundant endogenous nuclei in the healthy tissue, such as 1 H and 14 N, that can capture neutrons yielding a gamma ray in the first case, 1 H(n,c) 2 H, and a proton in the second one, 14 N(n,p) 14 C. The reaction 35 Cl(n,p) 35 S gives a small contribution with high-LET proton also. However, the amount of radiation produced is less than that produced by the particle and recoiling nucleus in the case of boron (5).…”

Design, Synthesis, and Biological Evaluation of Boron-Containing Macrocyclic Polyamines and Their Zinc(II) Complexes for Boron Neutron Capture Therapy

“…For successful BNCT, a high level of accumulation and selective delivery of 10 B into cancer cells are required. The design of effective BNCT agents requires the following criteria: (1) low systemic toxicity and higher uptake in tumor tissue than in normal tissue [tumor to blood (T/B) ratios should be greater than 3]; (2) 10 B must be retained in the tumor tissue but also be rapidly cleared from blood and normal tissues; and (3) the concentration of boron inside or near tumor cells must be ≥10 9 10 B atoms/cell (20–35 μg/gram of tumor tissue) . In this context, only two compounds, sodium mercaptoborate (BSH) 1 and l -4-boronophenylalanine (BPA) 2 (used as a complex with d -fructose) have been used for the clinical treatment of cancers such as malignant glioma, malignant melanoma, and recurrent head and neck cancer, which are not enough for treatment of multiple tumor types (Scheme ).…”