The Boron Advantage: The Evolution and Diversification of Boron’s Applications in Medicinal Chemistry

Abstract

In this review, the history of boron’s early use in drugs, and the history of the use of boron functional groups in medicinal chemistry applications are discussed. This includes diazaborines, boronic acids, benzoxaboroles, boron clusters, and carboranes. Furthermore, critical developments from these functional groups are highlighted along with recent developments, which exemplify potential prospects. Lastly, the application of boron in the form of a prodrug, softdrug, and as a nanocarrier are discussed to showcase boron’s emergence into new and exciting fields. Overall, we emphasize the evolution of organoboron therapeutic agents as privileged structures in medicinal chemistry and outline the impact that boron has had on drug discovery and development.

Design of DNA Intercalators Based on 4-Carboranyl-1,8-Naphthalimides: Investigation of Their DNA-Binding Ability and Anticancer Activity

“…The yield of products 8-11 and 16-19 achieved after isolation and purification by column chromatography ranged from 46% to 69% for conjugates containing ortho-carborane (8, 9, 16, and 17) and from 82% to 91% for conjugates containing meta-carborane (10, 11, 18, and 19). The modified anhydrides 6, 7, 14, and 15 and the modified naphthalimides 8-11 and 16-19 were characterized by 1 H-, 13 C-, and 11 B-NMR, FT-IR, MS, RP-HPLC (Figures S1-S86 (Electronic Supplementary Information, ESI)), and TLC.…”

“…In recent years, several studies have described the potential biomedical application of boron clusters, mostly as boron carriers for boron neutron capture therapy, pharmacophores, or modulators of different types of chemical compounds [11][12][13]. The properties of boron clusters that are critical to their use in medicinal chemistry include abiotic origin (these are therefore chemically and biologically orthogonal to native cellular components), the unique interaction properties of boron clusters and their derivatives with biomolecules, lipophilicity, amphiphilicity, hydrophobicity (depending on the chemical structure), chemical stability, susceptibility to functionalization, spherical or ellipsoidal geometry, and rigid three-dimensional arrangement [14,15].…”

Recent Developments to Cope the Antibacterial Resistance via β-Lactamase Inhibition

“…The interaction of boronic acids and their esters via covalent binding to the active site serine residue of certain proteases [91,92] provided the basis for their exploration as BLIs. The first report on the inhibition of the penicillinase by phenylboronic acid published by the Waley group in 1978 [93] led them to exploring of various boronic acids, such as BLIs, in the 1980s.…”

“…Vaborbactam: Vaborbactam, formerly RPX7009, the first FDA-approved cyclic boronic acid BLI [92], has shown the ability to inhibit ESBLs, class C BLAs, Class A carbapenemases (KPCs) [97][98][99][100], and some class D BLAs [94,100]. In addition, recent studies show that vaborbactam is also a weak inhibitor of class B MBLs [100,101].…”

Merging Electron Deficient Boronic Centers with Electron-Withdrawing Fluorine Substituents Results in Unique Properties of Fluorinated Phenylboronic Compounds

“…Therefore, the combination of a benzoxaborole unit and fluorine substituents in one molecule may result in increased biological activity. Very recently, the history of the use of boron functional groups in medicinal chemistry was reviewed [ 31 ]. Two comprehensive reviews on boron-containing heterocycles as pharmacological agents [ 32 ] and boron chemicals in drug discovery [ 33 ] were also recently published.…”