Wiley, European Chemical Societies Publishing
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’ pocket. The more potent of the two triazole regioisomers exhibits an IC50 of 3.7 nM versus MMP‐2 and IC50 of 46 nM versus MMP‐9.
Lutz, Marlon R. Jr; Flieger, Sebastian; Colorina, Andre; Wozny, John; Hosmane, Narayan S.; and Becker, Daniel P. Ph.D.. Carborane‐Containing Matrix Metalloprotease (MMP) Ligands as Candidates for Boron Neutron‐Capture Therapy (BNCT). ChemMedChem, , : , 2020. Retrieved from Loyola eCommons, Chemistry: Faculty Publications and Other Works, http://dx.doi.org/10.1002/cmdc.202000470
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Available for download on Tuesday, July 27, 2021