Chapter 6 - The serendipitous integration of small boron-embedded molecules into medicinal chemistry

Abstract

Despite the forte of organic medicinal chemistry, impediments as the dreaded drug-resistance phenomenon necessitate forging alternative drugs equipped with unorthodox warheads. Boron’s critical self-catenation and electronic-transmutation properties render its encompassing compounds as effective protagonists in antitumor, antimicrobial and anti-inflammatory warheads as well as diagnostics and carrier agents. In fact, the medicinal aptitudes of boron have been recognized and investigated for decades in one of the most elegant and infallible noninvasive protocols denoted as Boron Neutron Capture Therapy though the current agents of this protocol suffer from debilitating pharmacokinetic and pharmacodynamic drawbacks that manifest in terms of poor solubility and diminished uptake into malignant cells. Among the diverse families of boron-containing compounds, boronic acids have garnered notable consideration as they often display superior thermodynamically stable-structures and an overall diminished toxicity spectrum; consideration that manifested in the serendipitous discovery and subsequent approval of antitumor drugs Bortezomib and Ixazomib.