Recent developments with boron as a platform for novel drug design

ABSTRACT

Introduction: After decades of development, the medicinal chemistry of compounds that contain a single boron atom has matured to the present status of having equal rights with other branches of drug discovery, although it remains a relative newcomer. In contrast, the medicinal chemistry of boron clusters is less advanced, but it is expanding and may soon become a productive area of drug discovery.

Areas covered: The author reviews the current developments of medicinal chemistry of boron and its applications in drug design. First generation boron drugs that bear a single boron atom and second generation boron drugs that utilize boron clusters as pharmacophores or modulators of bioactive molecules are discussed. The advantages and gaps in our current understanding of boron medicinal chemistry, with a special focus on boron clusters, are highlighted.

Expert opinion: Boron is not a panacea for every drug discovery problem, but there is a good chance that it will become a useful addition to the medicinal chemistry tool box. The present status of boron resembles the medicinal chemistry status of fluorine three decades ago; indeed, currently, approximately 20% of pharmaceuticals on the market contain fluorine. The fact that novel boron compounds, especially those based on abiotic polyhedral boron hydrides, are currently unfamiliar could be advantageous because organisms may be less prone to developing resistance against boron cluster-based drugs.

KEYWORDS:

• Boron
• boronic acids
• boron clusters
• medicinal chemistry
• drug discovery

Article highlights

• Medicinal chemistry of boron proves its usefulness and novelty in offering clinically useful new drugs, drugs candidates, and molecular tools.

• Two branches of boron medicinal chemistry can be distinguished; the first utilizes single boron atom compounds, whereas the second utilizes boron clusters. In both cases, unique features of boron are exploited.

• An important advantage of boron use in drug design is to generate intellectual diversity in medicinal chemistry that pure synthetic organic chemistry or molecular biology cannot achieve alone.

• The fact that boron compounds, especially those based on polyhedral boron hydrides, will be unfamiliar to life has potential advantage because the active substances may be less prone to the development of resistance and may be more stable than carbon-based molecules in biological systems.

• Because the type of interactions of boron cluster drugs would likely be somewhat different from the key-lock systems that evolved in cells for billions of years, new drug targets can be targeted in a new way.

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Declaration of interest

Z Lesnikowski is supported by a grant from the National Science Center, Poland, grant 2015/16/W/ST5/00413 (project 2015-2019) and the Statutory Fund of Institute of Medical Biology PAS. The author have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.