Carborane‐Containing Matrix Metalloprotease (MMP) Ligands as Candidates for Boron Neutron‐Capture Therapy (BNCT)

<p> Based on the previously reported potent and selective sulfone hydroxamate inhibitors SC-76276, SC-78080 (SD-2590), and SC-77964, potent MMP inhibitors have been designed and synthesized to append a boron-rich carborane cluster by employing click chemistry to target tumor cells that are known to upregulate gelatinases. Docking against MMP-2 suggests binding involving the hydroxamate zinc-binding group, key H-bonds by the sulfone moiety with the peptide backbone residues Leu82 and Leu83, and a hydrophobic interaction with the deep P1&rsquo; pocket. The more potent of the two triazole regioisomers exhibits an IC50 of 3.7&emsp14;nM versus MMP-2 and IC50 of 46&emsp14;nM versus MMP-9.</p>