TY - JOUR
T1 - Carborane‐Containing Matrix Metalloprotease (MMP) Ligands as Candidates for Boron Neutron‐Capture Therapy (BNCT)
AU - Lutz, Marlon R
AU - Flieger, Sebastian
AU - Colorina, Andre
AU - Wozny, John
AU - Hosmane, Narayan S
AU - Becker, Daniel P
PY - 2020/7/27
Y1 - 2020/7/27
N2 - 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.
AB - 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.
KW - boron neutron capture therapy (BNCT)
KW - carborane
KW - matrix metalloproteinases (MMPs)
UR - https://ecommons.luc.edu/chemistry_facpubs/110
UR - https://doi.org/10.1002/cmdc.202000470
U2 - 10.1002/cmdc.202000470
DO - 10.1002/cmdc.202000470
M3 - Article
VL - 15
JO - Chemistry: Faculty Publications and Other Works
JF - Chemistry: Faculty Publications and Other Works
IS - 20
ER -