Boron Compounds in Medicinal Chemistry

Boron compounds have emerged as versatile scaffolds in drug discovery owing to their unique electronic and structural attributes. The vacant p orbital at the boron centre imparts Lewis acidity, enabling reversible covalent interactions with cis-diol motifs in biomolecules and forming covalent adducts with enzyme active sites. Clinically established agents such as bortezomib and more recent benzoxaborole drugs exemplify the capacity of boron-based motifs to modulate proteasome function and target aminoacyl-tRNA synthetases with high specificity. Beyond anticancer and antifungal applications, boron derivatives are under assessment for antimicrobial, anti-inflammatory, antiprotozoal and antiviral therapies, as well as in boron neutron capture therapy (BNCT) for tumours. Advances in synthetic methodology, computational prediction of acidity constants and structure–activity relationship (SAR) analysis have expanded the repertoire of boronic acids, benzoxaboroles, carboranes and other boron clusters, fostering optimised pharmacokinetic properties and target affinity. As a consequence, boron chemistry continues to shape innovative strategies in medicinal chemistry with global health implications.

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Boron Compounds in Medicinal Chemistry publication trend

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Technical terms

Boronic acid: An organoboron compound featuring a boron atom bonded to two hydroxyl groups and a carbon substituent, notable for reversible covalent interactions with diols.

Benzoxaborole: A cyclic boronic acid derivative in which boron is incorporated into a five-membered heterocycle, often exhibiting improved bioavailability and target specificity.

Lewis acidity: The ability of a compound, such as a boron centre, to accept an electron pair, underpinning reversible covalent binding to biomolecules.

Proteasome inhibitor: A molecule that impedes the proteasome enzyme complex responsible for protein degradation, a mode of action employed by certain boron-based therapeutics.

Structure–activity relationship (SAR): Correlation between the chemical structure of a molecule and its biological activity, guiding optimisation of drug candidates.

BNCT (Boron neutron capture therapy): A binary cancer treatment in which boron-containing agents selectively accumulate in tumour cells and, upon neutron irradiation, induce lethal radiation effects.

References

1. Acidity Constants of Boronic Acids as Simply as Possible: Experimental, Correlations, and Prediction. Molecules (2024).
2. Ethynyl-substituted benzosiloxaboroles: the role of C(π)⋯B interactions in their crystal packing and use in Cu( i )-catalyzed 1,3-dipolar cycloaddition. RSC Advances (2024).
3. Boron Chemicals in Drug Discovery and Development: Synthesis and Medicinal Perspective. Molecules (2022).